Trial Outcomes & Findings for A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors (NCT NCT02457793)

NCT ID: NCT02457793

Last Updated: 2018-11-20

Results Overview

DLTs include symptoms considered by the investigator to be possibly related to study drug.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

24 participants

Primary outcome timeframe

28 days (Cycle 1)

Results posted on

2018-11-20

Participant Flow

Participant milestones

Participant milestones
Measure	Not Assigned One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.	COB 20 mg + GDC 200 mg Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 40 mg + GDC 200 mg Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 200 mg Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 400 mg Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.	COB 100 mg + GDC 200 mg Concurrent or intermittent dosing of cobimetinib 100 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
Overall Study STARTED	1	5	3	5	4	6
Overall Study COMPLETED	0	1	0	0	0	0
Overall Study NOT COMPLETED	1	4	3	5	4	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Not Assigned One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.	COB 20 mg + GDC 200 mg Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 40 mg + GDC 200 mg Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 200 mg Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 400 mg Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.	COB 100 mg + GDC 200 mg Concurrent or intermittent dosing of cobimetinib 100 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
Overall Study Reason not specified	0	0	0	1	1	1
Overall Study Withdrawal by Subject	0	4	2	2	2	2
Overall Study Adverse Event	0	0	0	1	0	0
Overall Study Physician Decision	1	0	1	1	1	3

Baseline Characteristics

A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Not Assigned n=1 Participants One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.	COB 20 mg + GDC 200 mg n=5 Participants Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 40 mg + GDC 200 mg n=3 Participants Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 200 mg n=5 Participants Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 400 mg n=4 Participants Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.	COB 100 mg + GDC 200 mg n=6 Participants Concurrent or intermittent dosing of cobimetinib 100 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	Total n=24 Participants Total of all reporting groups
Age, Continuous	48.0 Years STANDARD_DEVIATION 9999 • n=99 Participants	53.0 Years STANDARD_DEVIATION 11.5 • n=107 Participants	57.3 Years STANDARD_DEVIATION 11.0 • n=206 Participants	51.6 Years STANDARD_DEVIATION 14.2 • n=7 Participants	52.3 Years STANDARD_DEVIATION 5.6 • n=31 Participants	59.7 Years STANDARD_DEVIATION 11.5 • n=30 Participants	54.6 Years STANDARD_DEVIATION 10.7 • n=3 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	5 Participants n=107 Participants	3 Participants n=206 Participants	4 Participants n=7 Participants	2 Participants n=31 Participants	3 Participants n=30 Participants	17 Participants n=3 Participants
Sex: Female, Male Male	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	2 Participants n=31 Participants	3 Participants n=30 Participants	7 Participants n=3 Participants

PRIMARY outcome

Timeframe: 28 days (Cycle 1)

Population: All participants.

DLTs include symptoms considered by the investigator to be possibly related to study drug.

Outcome measures

Outcome measures
Measure	Not Assigned n=1 Participants One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.	COB 20 mg + GDC 200 mg n=5 Participants Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 40 mg + GDC 200 mg n=3 Participants Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 200 mg n=5 Participants Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 400 mg n=4 Participants Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.	COB 100 mg + GDC 200 mg n=6 Participants Concurrent or intermittent dosing of cobimetinib 100 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
Number of Participants With Dose-Limiting Toxicities (DLTs) Diarrhoea	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Dose-Limiting Toxicities (DLTs) Myocardial infarction	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Dose-Limiting Toxicities (DLTs) Dermatitis Acneiform	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Dose-Limiting Toxicities (DLTs) Rash	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 15 months

Population: All participants.

An adverse event is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution.

Outcome measures

Outcome measures
Measure	Not Assigned n=1 Participants One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.	COB 20 mg + GDC 200 mg n=5 Participants Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 40 mg + GDC 200 mg n=3 Participants Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 200 mg n=5 Participants Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 400 mg n=4 Participants Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.	COB 100 mg + GDC 200 mg n=6 Participants Concurrent or intermittent dosing of cobimetinib 100 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
Percentage of Participants With at Least One Adverse Event	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants

PRIMARY outcome

Timeframe: Up to 15 months

Population: All participants.

AESIs were graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v4.0. AESIs included the following: Grade ≥ 1 retinal vein occlusion; Grade ≥ 2 visual disturbances (including events suggestive of serous retinopathy); Grade ≥ 3 rash for \> 7 days; Grade ≥ 3 diarrhea for \> 3 days; Grade ≥ 2 left ventricular ejection fraction (LVEF) decrease; Grade 3 hepatotoxicity; any dose-limiting toxicity (DLT); cases of potential drug-induced liver injury that include an elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (AST \> 3 × baseline value \[and above the upper limit of normal, ULN\]) in combination with either an elevated bilirubin ( \> 2 × ULN) or clinical jaundice; or suspected transmission of an infectious agent by either study drug.

Outcome measures

Outcome measures
Measure	Not Assigned n=1 Participants One participant was assigned to receive intermittent cobimetinib 80 milligrams (mg) + GDC 0994 200 mg) and did receive study drug. However, the participant diary was not returned, and the site was unable to document study dose administration.	COB 20 mg + GDC 200 mg n=5 Participants Concurrent or intermittent dosing of cobimetinib 20 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 40 mg + GDC 200 mg n=3 Participants Concurrent or intermittent dosing of cobimetinib 40 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 200 mg n=5 Participants Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.	COB 80 mg + GDC 400 mg n=4 Participants Concurrent or intermittent dosing of cobimetinib 80 mg, concurrent with GDC-0994 400 mg for 21 consecutive days, followed by 7 days off.	COB 100 mg + GDC 200 mg n=6 Participants Concurrent or intermittent dosing of cobimetinib 100 mg, concurrent with GDC-0994 200 mg for 21 consecutive days, followed by 7 days off.
Percentage of Participants With at Least One Adverse Event of Special Interest	100.0 percentage of participants	100 percentage of participants	33.3 percentage of participants	60.0 percentage of participants	75.0 percentage of participants	50.0 percentage of participants

PRIMARY outcome

Timeframe: Up to 15 months

Population: All participants.

A SAE is any experience that: results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically significant.