Trial Outcomes & Findings for The Effects of Vemurafenib + Cobimetinib on Immunity in Patients With Melanoma (NCT NCT01813214)

NCT ID: NCT01813214

Last Updated: 2019-02-26

Results Overview

CD8 T cell count per mm\^2 of tumor

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 5 participants
• Primary outcome timeframe: Day 1, Day 8, Day 15, Day 29
• Results posted on: 2019-02-26

Participant Flow

Participant milestones

Measure	Vemurafenib Monotherapy Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Vemurafenib	Vemurafenib + Cobimetinib Combination Therapy Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Cobimetinib will be given 60mg QD for 21 days on, then 7 days off, in a 28-day treatment cycle. Vemurafenib Cobimetinib
Overall Study STARTED	3	2
Overall Study COMPLETED	3	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Effects of Vemurafenib + Cobimetinib on Immunity in Patients With Melanoma

Baseline characteristics by cohort

Measure	Vemurafenib Monotherapy n=3 Participants Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Vemurafenib	Vemurafenib + Cobimetinib Combination Therapy n=2 Participants Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Cobimetinib will be given 60mg QD for 21 days on, then 7 days off, in a 28-day treatment cycle. Vemurafenib Cobimetinib	Total n=5 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1, Day 8, Day 15, Day 29

CD8 T cell count per mm^2 of tumor

Outcome measures

Measure	Vemurafenib Monotherapy n=3 Participants Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Vemurafenib	Vemurafenib + Cobimetinib Combination Therapy n=2 Participants Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Cobimetinib will be given 60mg QD for 21 days on, then 7 days off, in a 28-day treatment cycle. Vemurafenib Cobimetinib
Time Course by Which Vemurafenib and Cobimetinib Increases T Cell Infiltration Day 1	7.24 CD8 T cell count per mm^2 of tumor Standard Deviation 3.68	18.95 CD8 T cell count per mm^2 of tumor Standard Deviation 2.64
Time Course by Which Vemurafenib and Cobimetinib Increases T Cell Infiltration Day 8	133.29 CD8 T cell count per mm^2 of tumor Standard Deviation 82.22	195.77 CD8 T cell count per mm^2 of tumor Standard Deviation 185.88
Time Course by Which Vemurafenib and Cobimetinib Increases T Cell Infiltration Day 15	275.08 CD8 T cell count per mm^2 of tumor Standard Deviation 125.96	51.85 CD8 T cell count per mm^2 of tumor Standard Deviation 30.09
Time Course by Which Vemurafenib and Cobimetinib Increases T Cell Infiltration Day 29	197.20 CD8 T cell count per mm^2 of tumor Standard Deviation 266.37	152.72 CD8 T cell count per mm^2 of tumor Standard Deviation 65.54

PRIMARY outcome

Timeframe: Day 1, Day 8, Day 15, Day 29

CD4 T cell count per mm^2 of tumor

Outcome measures

Measure	Vemurafenib Monotherapy n=3 Participants Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Vemurafenib	Vemurafenib + Cobimetinib Combination Therapy n=2 Participants Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Cobimetinib will be given 60mg QD for 21 days on, then 7 days off, in a 28-day treatment cycle. Vemurafenib Cobimetinib
Time Course by Which Vemurafenib and Cobimetinib Increases T Cell Infiltration Day 1	14.06 CD4 T cell count per mm^2 of tumor Standard Deviation 30.36	99.12 CD4 T cell count per mm^2 of tumor Standard Deviation 18.73
Time Course by Which Vemurafenib and Cobimetinib Increases T Cell Infiltration Day 8	62.17 CD4 T cell count per mm^2 of tumor Standard Deviation 40.77	51.70 CD4 T cell count per mm^2 of tumor Standard Deviation 12.12
Time Course by Which Vemurafenib and Cobimetinib Increases T Cell Infiltration Day 15	186.10 CD4 T cell count per mm^2 of tumor Standard Deviation 80.53	144.50 CD4 T cell count per mm^2 of tumor Standard Deviation 46.65
Time Course by Which Vemurafenib and Cobimetinib Increases T Cell Infiltration Day 29	218.44 CD4 T cell count per mm^2 of tumor Standard Deviation 268.82	580.1 CD4 T cell count per mm^2 of tumor Standard Deviation 419.53

SECONDARY outcome

Timeframe: 2 months

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT and/or 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

Outcome measures

Measure	Vemurafenib Monotherapy n=3 Participants Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Vemurafenib	Vemurafenib + Cobimetinib Combination Therapy n=2 Participants Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Cobimetinib will be given 60mg QD for 21 days on, then 7 days off, in a 28-day treatment cycle. Vemurafenib Cobimetinib
Number of Participants With Tumor Response	3 Participants	2 Participants

Adverse Events

Vemurafenib Monotherapy

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Vemurafenib + Cobimetinib Combination Therapy

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Vemurafenib Monotherapy n=3 participants at risk Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Vemurafenib	Vemurafenib + Cobimetinib Combination Therapy n=2 participants at risk Vemurafenib 960 mg po BID until unacceptable toxicity or progression of disease Cobimetinib will be given 60mg QD for 21 days on, then 7 days off, in a 28-day treatment cycle. Vemurafenib Cobimetinib
General disorders Dehydration	33.3% 1/3 • Number of events 1	0.00% 0/2
Nervous system disorders Headache	33.3% 1/3 • Number of events 1	50.0% 1/2 • Number of events 1
Gastrointestinal disorders Hyperuricemia	0.00% 0/3	50.0% 1/2 • Number of events 1
Blood and lymphatic system disorders Lymphopenia	66.7% 2/3 • Number of events 2	50.0% 1/2 • Number of events 1
General disorders Nausea	0.00% 0/3	50.0% 1/2 • Number of events 1
Gastrointestinal disorders Vomiting	66.7% 2/3 • Number of events 2	0.00% 0/2
Musculoskeletal and connective tissue disorders Extremity Pain	33.3% 1/3 • Number of events 1	0.00% 0/2
Ear and labyrinth disorders Photosensitivity	0.00% 0/3	50.0% 1/2 • Number of events 1
Skin and subcutaneous tissue disorders Rash-maculopapular	33.3% 1/3 • Number of events 1	0.00% 0/2
Eye disorders Sub-retinal edema	33.3% 1/3 • Number of events 1	0.00% 0/2
Hepatobiliary disorders Elevated ALT	33.3% 1/3 • Number of events 1	50.0% 1/2 • Number of events 1
Hepatobiliary disorders Elevated AST	0.00% 0/3	50.0% 1/2 • Number of events 1

Additional Information

Dr Michael Atkins

Lombardi Comprehensive Cancer Center

Phone: 202-687-2795

Email: mba41@georgetown.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place