Trial Outcomes & Findings for Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D (NCT NCT01833143)

Last Updated: 2020-08-04

Results Overview

The following evaluations will be conducted to assess the efficacy of bortezomib - radiographic response rate by RECIST v1.1. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

2 years

Results posted on

2020-08-04

Participant Flow

Participant milestones

Participant milestones
Measure	Bortezomib Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay \> 2 weeks, or at the discretion of the treating physician or patient.
Overall Study STARTED	17
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Bortezomib Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay \> 2 weeks, or at the discretion of the treating physician or patient.
Overall Study Not Treated	1

Baseline Characteristics

Bortezomib in KRAS-Mutant Non-Small Cell Lung Cancer in Never Smokers or Those With KRAS G12D

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bortezomib n=17 Participants Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay \> 2 weeks, or at the discretion of the treating physician or patient.
Age, Continuous	67 years n=99 Participants
Sex: Female, Male Female	8 Participants n=99 Participants
Sex: Female, Male Male	9 Participants n=99 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=99 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=99 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	3 Participants n=99 Participants
Race (NIH/OMB) White	13 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants
Region of Enrollment United States	17 Participants n=99 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Bortezomib n=17 Participants Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay \> 2 weeks, or at the discretion of the treating physician or patient.
Radiographic Response Rate Partial Response	1 Participants
Radiographic Response Rate Stable Disease	6 Participants
Radiographic Response Rate Progression of Disease	10 Participants

SECONDARY outcome

Timeframe: 2 years

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Outcome measures

Outcome measures
Measure	Bortezomib n=17 Participants Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay \> 2 weeks, or at the discretion of the treating physician or patient.
Progression Free Survival	1 months Interval 1.0 to 6.0

SECONDARY outcome

Timeframe: 2 years

Before each drug dose, the patient will be evaluated for possible toxicities that may have occurred after the previous dose(s). Toxicities are to be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE v4.0,).

Outcome measures

Outcome measures
Measure	Bortezomib n=17 Participants Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay \> 2 weeks, or at the discretion of the treating physician or patient.
Participants Evaluated for Toxicity	17 Participants

SECONDARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Bortezomib n=17 Participants Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay \> 2 weeks, or at the discretion of the treating physician or patient.
Overall Survival	13 months Interval 6.0 to 30.0

Adverse Events

Bortezomib

Serious events: 4 serious events

Other events: 16 other events

Deaths: 12 deaths

Serious adverse events

Serious adverse events
Measure	Bortezomib n=17 participants at risk Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay \> 2 weeks, or at the discretion of the treating physician or patient.
Respiratory, thoracic and mediastinal disorders Dyspnea	11.8% 2/17 • 2 years
General disorders Fever	5.9% 1/17 • 2 years
Blood and lymphatic system disorders Leukocytosis	5.9% 1/17 • 2 years
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.9% 1/17 • 2 years

Other adverse events

Other adverse events
Measure	Bortezomib n=17 participants at risk Bortezomib will be administered by subcutaneous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11) at 1.3 mg/m2/dose followed by a 10-day rest period for a 21 day cycle. Dose modifications are permitted as per a prescribed algorithm. Acyclovir at 400mg daily is recommended as prophylaxis for herpes zoster. Restaging scans, with evaluation of response, will be done every 2 cycles (6 weeks of treatment ± 7 days). Treatment will continue until clinical disease progression, unacceptable toxicity, treatment delay \> 2 weeks, or at the discretion of the treating physician or patient.
General disorders Fatigue	47.1% 8/17 • 2 years
Gastrointestinal disorders Diarrhea	35.3% 6/17 • 2 years
Metabolism and nutrition disorders Anorexia	23.5% 4/17 • 2 years
Gastrointestinal disorders Constipation	23.5% 4/17 • 2 years
Gastrointestinal disorders Nausea	23.5% 4/17 • 2 years
Skin and subcutaneous tissue disorders Papulopustular rash	23.5% 4/17 • 2 years
Nervous system disorders Headache	17.6% 3/17 • 2 years
General disorders Localized edema	17.6% 3/17 • 2 years
General disorders Fever	11.8% 2/17 • 2 years
General disorders Injection site reaction	11.8% 2/17 • 2 years
Gastrointestinal disorders Mucositis oral	11.8% 2/17 • 2 years
Nervous system disorders Peripheral motor neuropathy	11.8% 2/17 • 2 years
Nervous system disorders Peripheral sensory neuropathy	11.8% 2/17 • 2 years
Investigations Platelet count decreased	11.8% 2/17 • 2 years
Gastrointestinal disorders Vomiting	11.8% 2/17 • 2 years
Musculoskeletal and connective tissue disorders Back pain	11.8% 2/17 • 2 years
Respiratory, thoracic and mediastinal disorders Cough	5.9% 1/17 • 2 years
Psychiatric disorders Depression	5.9% 1/17 • 2 years
Gastrointestinal disorders Dry mouth	5.9% 1/17 • 2 years
Eye disorders Eye pain	5.9% 1/17 • 2 years
General disorders Flu like symptoms	5.9% 1/17 • 2 years
Gastrointestinal disorders Hemorrhoids	5.9% 1/17 • 2 years
Endocrine disorders Hypothyroidism	5.9% 1/17 • 2 years
Musculoskeletal and connective tissue disorders Pain in extremity	5.9% 1/17 • 2 years
Skin and subcutaneous tissue disorders Rash maculo-papular	5.9% 1/17 • 2 years

Additional Information

Gregory Riely, MD, PhD

Memorial Sloan Kettering Cancer Center

Phone: 646-608-3913

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place