Trial Outcomes & Findings for Testing of the Anti Cancer Drugs CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib) in Advanced Stage Non-small Cell Lung Cancer (NCT NCT04250545)

Last Updated: 2026-05-01

Results Overview

Will be evaluated according to dose-limiting toxicities during cycle 1 graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE1

Target enrollment

22 participants

Primary outcome timeframe

Up to 28 days

Results posted on

2026-05-01

Participant Flow

Twenty-two patients were enrolled in the study. All patients started treatment and were included in the final analysis. The study was closed prematurely due to drug supply issues.

Participant milestones

Participant milestones
Measure	Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 2 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food) Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken with food. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach) Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken on an empty stomach. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO
Overall Study STARTED	14	5	3
Overall Study COMPLETED	14	5	3
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Testing of the Anti Cancer Drugs CB-839 HCl (Telaglenastat) and MLN0128 (Sapanisertib) in Advanced Stage Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg n=14 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 2 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food) n=5 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken with food. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach) n=3 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken on an empty stomach. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Total n=22 Participants Total of all reporting groups
Age, Continuous	67 years n=14 Participants	66 years n=34 Participants	75 years n=69 Participants	67 years n=140 Participants
Sex: Female, Male Female	7 Participants n=14 Participants	0 Participants n=34 Participants	3 Participants n=69 Participants	10 Participants n=140 Participants
Sex: Female, Male Male	7 Participants n=14 Participants	5 Participants n=34 Participants	0 Participants n=69 Participants	12 Participants n=140 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	1 Participants n=140 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=14 Participants	5 Participants n=34 Participants	3 Participants n=69 Participants	19 Participants n=140 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	2 Participants n=140 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	0 Participants n=140 Participants
Race (NIH/OMB) Asian	3 Participants n=14 Participants	0 Participants n=34 Participants	1 Participants n=69 Participants	4 Participants n=140 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	0 Participants n=140 Participants
Race (NIH/OMB) Black or African American	1 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	1 Participants n=140 Participants
Race (NIH/OMB) White	7 Participants n=14 Participants	5 Participants n=34 Participants	2 Participants n=69 Participants	14 Participants n=140 Participants
Race (NIH/OMB) More than one race	0 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	0 Participants n=140 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=14 Participants	0 Participants n=34 Participants	0 Participants n=69 Participants	3 Participants n=140 Participants
Region of Enrollment United States	14 participants n=14 Participants	5 participants n=34 Participants	3 participants n=69 Participants	22 participants n=140 Participants

PRIMARY outcome

Timeframe: Up to 28 days

Population: The study was closed prematurely due to drug supply issues; therefore, the maximum tolerated dose was not determined.

Will be evaluated according to dose-limiting toxicities during cycle 1 graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Outcome measures

Outcome measures
Measure	Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach) Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken on an empty stomach. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg n=22 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 2 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food) Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken with food. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO
Maximum Tolerated Dose/Recommended Phase II Dose of MLN0128 (Sapanisertib) and CB-839 HCl (Telaglenastat) in Combination (Dose-escalation)	—	NA mg The study was closed prematurely due to drug supply issues; therefore, the maximum tolerated dose was not determined.	—

PRIMARY outcome

Timeframe: Up to 27 months

Population: Response was evaluated in patients who received at least one cycle of therapy

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions or Disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach) n=3 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken on an empty stomach. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg n=11 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 2 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food) n=3 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken with food. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO
Number of Subjects With Overall Response	1 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 27 months

Median PFS will be determined using the Kaplan-Meier method. PFS is defined as the duration of time from the start of treatment to the time of progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions, or appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach) n=3 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken on an empty stomach. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg n=14 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 2 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food) n=5 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken with food. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO
Median Progression Free Survival (PFS) (Dose-expansion)	4.3 months Interval 1.6 to 8.1	3.6 months Interval 1.2 to 5.2	2.9 months Interval 1.4 to 4.1

SECONDARY outcome

Timeframe: Up to 27 months

Population: Response was evaluated in patients who received at least one cycle of therapy

Outcome measures

Outcome measures
Measure	Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach) n=3 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken on an empty stomach. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg n=11 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 2 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food) n=3 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken with food. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO
Objective Response Rate (ORR)	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 27 months

Will be evaluated by Kaplan-Meier estimates. PFS is defined as the duration of time from the start of treatment to the time of progression or death, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or the appearance of new lesions, or appearance of one or more new non-target lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach) n=3 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken on an empty stomach. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg n=14 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 2 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food) n=5 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken with food. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO
Progression Free Survival (PFS)	4.3 months Interval 1.6 to 8.1	3.6 months Interval 1.2 to 5.2	2.9 months Interval 1.4 to 4.1

SECONDARY outcome

Timeframe: Up to 27 months

Population: Response was evaluated in patients who received at least one cycle of therapy

DCR will be assessed by RECIST 1.1 criteria. DCR is defined as the proportion of patients who achieved either a complete response, partial response, or stable disease at any point during the treatment period. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions or Disappearance of all non-target lesions and normalization of tumor marker level; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study; DCR = CR + PR + SD.

Outcome measures

Outcome measures
Measure	Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach) n=3 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken on an empty stomach. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg n=14 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 2 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food) n=5 Participants Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken with food. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO
Disease Control Rate (DCR)	2 Participants	7 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 27 months

Population: The study was closed prematurely due to drug supply issues; therefore, this measure was not analyzed.

Change in tumor uptake of radio-labelled glutamine on PET from baseline to cycle 1 day 8 will be quantified by the standardized uptake value maximum (SUVmax) (a standard PET parameter) in the largest measurable lesion. The before and after 18F-Gln PET values will be compared using log(after/before) as a measure of relative change.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 27 months

Population: The study was closed prematurely due to drug supply issues; therefore, this measure was not analyzed.

Genomic and metabolic signatures will be correlated with responses. Changes in glutamine, glutamate, aspartate, and asparagine will be measured, and responders will be compared to non-responders using a two-sample t-test or Wilcoxon test.

Outcome measures

Outcome data not reported

Adverse Events

Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg

Serious events: 6 serious events

Other events: 14 other events

Deaths: 11 deaths

Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food)

Serious events: 4 serious events

Other events: 5 other events

Deaths: 2 deaths

Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach)

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Paul Frankel, Ph.D.

City of Hope

Phone: 6262185265

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Serious adverse events
Measure	Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg n=14 participants at risk Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 2 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food) n=5 participants at risk Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken with food. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach) n=3 participants at risk Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken on an empty stomach. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO
Cardiac disorders Pericardial effusion	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fatigue	14.3% 2/14 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fever	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Pain	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Bacteremia	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Lung infection	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Urinary tract infection	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Blood bilirubin increased	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Investigations Cardiac troponin I increased	7.1% 1/14 • Number of events 8 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypercalcemia	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hyponatremia	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Metabolism and nutrition disorders Hypophosphatemia	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Nervous system disorders Stroke	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Dyspnea	14.3% 2/14 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Hypoxia	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Pleural effusion	7.1% 1/14 • Number of events 6 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Respiratory, thoracic and mediastinal disorders Stridor	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Vascular disorders Thromboembolic event	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.

Other adverse events
Measure	Dose Level 1 - MLN0128 2 mg QD + CB-839 HCl 800 mg n=14 participants at risk Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 2 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 1a - MLN0128 3 mg QD + CB-839 HCl 800 mg (With Food) n=5 participants at risk Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken with food. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO	Dose Level 2 - MLN0128 3 mg QD + CB-839 HCl 800 mg (Empty Stomach) n=3 participants at risk Patients receive 800 mg of glutaminase inhibitor CB-839 hydrochloride PO BID and 3 mg sapanisertib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Regimen taken on an empty stomach. Sapanisertib: Given PO Telaglenastat Hydrochloride: Given PO
Ear and labyrinth disorders Vertigo	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Cataract	7.1% 1/14 • Number of events 6 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Blood and lymphatic system disorders Anemia	42.9% 6/14 • Number of events 17 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	60.0% 3/5 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	66.7% 2/3 • Number of events 7 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Blood and lymphatic system disorders Hemoptysis	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Blood and lymphatic system disorders Lymph node pain	7.1% 1/14 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Atrial fibrillation	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Palpitations	7.1% 1/14 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Pericardial effusion	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Cardiac disorders Sinus tachycardia	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Ear and labyrinth disorders Hearing impaired	7.1% 1/14 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders Periorbital edema	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders R eye floater	7.1% 1/14 • Number of events 8 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders sensitive to light (vision)	7.1% 1/14 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Eye disorders sensitivity to light	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Abdominal pain	21.4% 3/14 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	40.0% 2/5 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Bloating	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Blood in Stool	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Constipation	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Diarrhea	28.6% 4/14 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	66.7% 2/3 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dry mouth	14.3% 2/14 • Number of events 11 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dyspepsia	14.3% 2/14 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Dysphagia	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Flatulence	7.1% 1/14 • Number of events 4 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Mucositis oral	21.4% 3/14 • Number of events 6 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	66.7% 2/3 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Nausea	71.4% 10/14 • Number of events 24 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	80.0% 4/5 • Number of events 11 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	100.0% 3/3 • Number of events 13 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Oral pain	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Gastrointestinal disorders Vomiting	50.0% 7/14 • Number of events 16 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	60.0% 3/5 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	66.7% 2/3 • Number of events 5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Chills	7.1% 1/14 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Edema face	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Edema limbs	14.3% 2/14 • Number of events 3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fatigue	57.1% 8/14 • Number of events 36 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	100.0% 3/3 • Number of events 10 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Fever	7.1% 1/14 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Gait disturbance	7.1% 1/14 • Number of events 8 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Non-cardiac chest pain	14.3% 2/14 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
General disorders Pain	14.3% 2/14 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Lung infection	14.3% 2/14 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	40.0% 2/5 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Sepsis	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Upper respiratory infection	7.1% 1/14 • Number of events 2 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/3 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.
Infections and infestations Urinary tract infection	0.00% 0/14 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	0.00% 0/5 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.	33.3% 1/3 • Number of events 1 • Adverse events were assessed from the time of initial treatment until 30 days post-discontinuation of treatment. Adverse events occurred over a period of 4.4 years. "Other Adverse Events" include all events that were not severe adverse events regardless of grade or relation to treatment.