AzTrials
AzTrials

Malignant MelanomaPhase 1NCT01656642

A Phase 1b Study of Atezolizumab in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Participants With BRAFV600-Mutation Positive Metastatic Melanoma

A Phase 1 study testing Atezolizumab, Cobimetinib and Vemurafenib in people with Malignant Melanoma, run by Genentech, Inc. at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is an open-label, multicenter, Phase Ib, dose-escalation and cohort-expansion study of atezolizumab (anti-programmed death-ligand 1 [PD-L1] antibody) in combination with vemurafenib or vemurafenib plus cobimetinib in participants with BRAFV600-mutation positive metastatic melanoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Melanoma
What is being tested?
Atezolizumab, Cobimetinib and Vemurafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
67 participants
Where
8 sitesUnited States
Study dates
13 Aug 2012to 25 Mar 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologic or cytologic documentation of metastatic or Stage IIIc unresectable melanoma, with BRAFV600 mutation as assessed by BRAFV600 Mutation Test. Origin of the primary tumor may be of skin, mucosal, or acral locations but not of uveal origin. Participants having an unknown primary tumor may be eligible if uveal melanoma can be ruled out
  • Eastern Cooperative Oncology Group performance status of 0 or 1
  • Adequate hematologic and end organ function
  • Measurable disease per RECIST v1.1
  • For women of childbearing potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use two effective forms of contraceptive methods including at least one that results in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 6 months after the last dose of study drug
  • For men, agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm
  • Agreement to mandatory archival tissue or fresh biopsy
  • Agreement to the collection of serial fresh lesion samples (required, if feasible, for entry into Escalation Cohorts 4 and Expansion Cohorts A \& B and optional, but encouraged in Escalation Cohorts 2 \& 3 and Expansion Cohort C)

Who cannot join

  • Receipt of prior systemic anti-cancer therapy for unresectable, locally advanced or metastatic melanoma
  • Receipt of prior immunomodulatory agents, including programmed death-1 or PD-L1 targeted therapy or cytotoxic T-lymphocyte-associated antigen 4 targeted therapy including ipilimumab (this exclusion criterion does not apply to participants enrolled in Expansion Cohort A)
  • Receipt of prior mitogen-activated protein kinase inhibitor pathway agents including mitogen-activated protein kinase inhibitor and BRAF kinase inhibitor
  • Major surgical procedure within 28 days prior to Day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Radiotherapy less than or equal to (<=) 7 days prior to Day 1
  • Adverse events from prior anti-cancer therapy that have not resolved to Grade <= 1 except for alopecia
Show all 12Show fewer
  • Any active malignancy (other than BRAF-mutated melanoma) or a previous malignancy within the past 3 years
  • For participants to be enrolled into the vemurafenib+cobimetinib+ atezolizumab cohorts: history of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion, or neovascular macular degeneration
  • Pregnant or breastfeeding women
  • Intake of St. John's wort or hyperforin (potent cytochrome P450 [CYP] 3A4 enzyme inducer) or grapefruit juice (potent CYP3A4 enzyme inhibitor) within 7 days preceding the start of study treatment to the end of treatment
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation or known hypersensitivity to any component of cobimetinib or vemurafenib
  • Inability to comply with study and follow-up procedures

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • University of Colorado Health Science Center; Biomedical Research Bldg. Room 511

    Aurora, Colorado, 80045

  • Massachusetts General Hospital.

    Boston, Massachusetts, 02114

  • Dana Farber Can Ins

    Boston, Massachusetts, 02215

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • UCLA

    Los Angeles, California, 90024

  • The Angeles Clinic and Research Institute - W LA Office

    Los Angeles, California, 90025

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Florida Cancer Specialists - Sarasota

    Sarasota, Florida, 34232

Other trials in United States

About this study

Official title: A Phase Ib, Open-Label Study of The Safety and Pharmacology of Atezolizumab (Anti PD-L1 Antibody) Administered in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Patients With BRAFV600-Mutation Positive Metastatic Melanoma

This is an open-label, multicenter, Phase Ib, dose-escalation and cohort-expansion study of atezolizumab (anti-programmed death-ligand 1 [PD-L1] antibody) in combination with vemurafenib or vemurafenib plus cobimetinib in participants with BRAFV600-mutation positive metastatic melanoma. Enrolled participants may continue treatment until they are no longer experiencing clinical benefit as assessed by the investigator and in alignment with the protocol.

Being tested
Atezolizumab, Cobimetinib, Vemurafenib
Keywords
PD-L1, PD-1, PDL1, antiPD-L1, MPDL3280A, Melanoma, BRAF, MPDL320A
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called MPDL3280A, an engineered anti-PD-L1 antibody, TECENTRIQ, RO5541267

    Atezolizumab will be administered q3w or q2w.

  • CobimetinibDrug

    Also called GDC-0973, XL518, Cotellic, RO5514041

    Oral repeating dose

  • VemurafenibDrug

    Also called Zelboraf, RO5185426

    Oral repeating dose, depending on arm/cohort

Study groups in NCT01656642
Study groupRoleWhat they receive
Cohort 1 (C1): Ate+Vem - No Run-inExperimentalParticipants will receive atezolizumab (Ate) 1200 milligrams (mg) every 3 weeks (q3w) along with vemurafenib (Vem) 720 mg twice daily (BID) for 21 days in each cycle followed by 7 days off treatment (28-day cycle). Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent occurs.
Receives: Drug: Atezolizumab; Drug: Vemurafenib
Cohort 2 (C2): Ate+Vem (56 Day Run-in)ExperimentalRun-in period (56 days): participants will receive vemurafenib 960 mg orally BID from Day 1 to 49 and vemurafenib 720 mg orally BID from Day 50 to 56. Combination treatment period: Participants will receive fixed dose of atezolizumab 1200 mg intravenous (IV) q3w in combination with vemurafenib 720 mg orally BID in 21 days cycle.
Receives: Drug: Atezolizumab; Drug: Vemurafenib
Cohort 3 (C3): Ate+Vem (28 Day Run-in)ExperimentalRun-in period (28 days): participants will receive vemurafenib 960 mg orally BID for 21 days, then vemurafenib 720 mg orally BID for 7 days. Combination treatment period: Participants will receive fixed dose of atezolizumab 1200 mg IV q3w in combination with vemurafenib 720 mg orally BID in 21 days cycle.
Receives: Drug: Atezolizumab; Drug: Vemurafenib
Cohort 4 (C4): Ate+Vem+Cob (28 Day Run-in)ExperimentalRun-in period (28 days): participants will receive vemurafenib 960 mg orally BID for 21 days, then vemurafenib 720 mg orally BID for 7 days in combination with cobimetinib (Cob) 60 mg IV once daily, 21 days on/7 days off schedule (21/7). Combination treatment period: Participants will receive fixed dose of atezolizumab 800 mg IV every 2 weeks (q2w) in combination with vemurafenib 720 mg orally BID and cobimetinib 60 mg orally once daily 21/7 in 28 days cycle.
Receives: Drug: Atezolizumab; Drug: Cobimetinib; Drug: Vemurafenib
ECA: Ate+Vem+Cob (Mandatory Biopsy PD)ExperimentalExpansion Cohort A (ECA): Approximately 10 participants who experienced disease progression (PD) after receiving prior checkpoint inhibitor therapy will be enrolled and treated with atezolizumab plus (+) vemurafenib + cobimetinib. Serial biopsy tissue sample collections of accessible lesions will be mandatory for all participants enrolled in this cohort. The doses will be decided based on the results of Cohorts 1-4.
Receives: Drug: Atezolizumab; Drug: Cobimetinib; Drug: Vemurafenib
ECB: Ate+Vem+Cob (Mandatory Biopsy)ExperimentalExpansion Cohort B (ECB): Approximately 20 participants will be enrolled and treated with atezolizumab + vemurafenib + cobimetinib. Serial biopsy tissue sample collections of accessible lesions will be mandatory for all participants. The doses will be decided based on the results of Cohorts 1-4.
Receives: Drug: Atezolizumab; Drug: Cobimetinib; Drug: Vemurafenib
ECC: Ate+Vem+Cob (No Mandatory Biopsy)ExperimentalExpansion Cohort C (ECC): Approximately 10 participants who experienced disease progression after receiving prior checkpoint inhibitor therapy will be enrolled and treated with atezolizumab + vemurafenib + cobimetinib. Serial biopsy tissue sample collections will be optional for all participants enrolled in this cohort. The doses will be decided based on the results of Cohorts 1-4.
Receives: Drug: Atezolizumab; Drug: Cobimetinib; Drug: Vemurafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Dose Limiting Toxicities

    Measured: 21 days (or 28 days for Cohort 4) following the first administration of atezolizumab

  2. Percentage of Participants With Adverse Events

    Measured: Baseline up to approximately 6 years

Secondary outcomes (17)

  1. Area Under the Concentration-Time Curve (AUC) of Atezolizumab

    Measured: Predose (0 hour), 30 minutes postdose on Day (D) 1 of Cycles (C) 1, 2; predose on D15, D8 of C1; predose on D1 of C3, 4, 5, 7, 8, every 8 cycles thereafter up to 90 days after end of treatment visit (up to approximately 6 years) (Cycle=28 days)

  2. Maximum Serum Concentration of Atezolizumab

    Measured: Predose (0 hour), 30 minutes postdose on Day (D) 1 of Cycles (C) 1, 2; predose on D15, D8 of C1; predose on D1 of C3, 4, 5, 7, 8, every 8 cycles thereafter up to 90 days after end of treatment visit (up to approximately 6 years) (Cycle=28 days)

  3. Maximum Plasma Concentration of Vemurafenib

    Measured: Run-in period: predose (0 hour) on D1, 8, and 22, 3 hours postdose on D22; combination treatment period: predose (0 hour) on D1 of C1 and 2, 3 hours postdose on D1 of C2 (Cycle = 28 days)

  4. Minimum Observed Plasma Trough Concentration (Cmin) of Vemurafenib

    Measured: Run-in period: predose (0 hour) on D1, 8, and 22; combination treatment period: predose (0 hour) on D1 of C1 and 2 (Cycle = 28 days)

  5. Maximum Plasma Concentration of Cobimetinib

    Measured: Run-in period: predose (0 hour) on D1, 8, and 22; combination treatment period: predose (0 hour) on D1 and 15 of C1 and D15 of C2, 3 hours postdose on D15 of Cycle 1 (Cycle = 28 days)

  6. Cmin of Cobimetinib

    Measured: Run-in period: predose (0 hour) on D1, 8, and 22; combination treatment period: predose (0 hour) on D1 and 15 of C1 and D15 of C2 (Cycle = 28 days)

  7. Percentage of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)

    Measured: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years)

  8. Percentage of Participants with Objective Response According to RECIST v1.1

    Measured: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years)

  9. Percentage of Participants with Objective Response According to Immune-Related Response Criteria (irRC)

    Measured: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years)

  10. Duration of Objective Response According to RECIST v1.1

    Measured: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years)

  11. Duration of Objective Response According to irRC

    Measured: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years)

  12. Progression Free Survival According to RECIST v1.1

    Measured: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years)

  13. Progression Free Survival According to irRC

    Measured: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years)

  14. Overall Survival Duration

    Measured: Baseline until death up to 6 years

  15. Mean Atezolizumab Dose

    Measured: Approximately 12 months

  16. Total Number of Atezolizumab Cycles

    Measured: Approximately 12 months

  17. Percentage of Participants With Anti-Atezolizumab Antibodies

    Measured: Predose (0 hour) on D1 (run-in period), predose (0 hour) on D1 of C2, 3, 4, 8, every 8 cycles thereafter up to 90 days after end of treatment visit (up to approximately 6 years) (Cycle=28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Aug 2012 (estimated)
  2. Study start13 Aug 2012
  3. Primary completion25 Mar 2020
  4. Study completion25 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
67 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01656642
Sponsor's protocol ID
GP28384
Other IDs
2012-002738-35
Status last verified
Jul 2020
First submitted
1 Aug 2012
Last updated
21 Jul 2020
Results posted
No

Publications

  • Sullivan RJ, Hamid O, Gonzalez R, Infante JR, Patel MR, Hodi FS, Lewis KD, Tawbi HA, Hernandez G, Wongchenko MJ, Chang Y, Roberts L, Ballinger M, Yan Y, Cha E, Hwu P. Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients. Nat Med. 2019 Jun;25(6):929-935. doi: 10.1038/s41591-019-0474-7. Epub 2019 Jun 6.

    PubMed 31171876

  • Ackerman A, Klein O, McDermott DF, Wang W, Ibrahim N, Lawrence DP, Gunturi A, Flaherty KT, Hodi FS, Kefford R, Menzies AM, Atkins MB, Long GV, Sullivan RJ. Outcomes of patients with metastatic melanoma treated with immunotherapy prior to or after BRAF inhibitors. Cancer. 2014 Jun 1;120(11):1695-701. doi: 10.1002/cncr.28620. Epub 2014 Feb 27.

    PubMed 24577748

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Atezolizumab, Cobimetinib and Vemurafenib in people with Malignant Melanoma, run by Genentech, Inc. at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Dose Limiting Toxicities (time frame: 21 days (or 28 days for Cohort 4) following the first administration of atezolizumab). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01656642, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in