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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-003329-27 | EudraCT Number |
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This is a Phase Ib, open-label, multicenter study designed to assess the safety, tolerability, and pharmacokinetics of coadministration of intravenous (IV) dosing of atezolizumab (an engineered anti-programmed death-ligand 1 [anti-PD-L1] antibody) and oral dosing of cobimetinib in participants with metastatic or locally advanced cancer for which no standard therapy exists.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose-Escalation: Cobimetinib, Atezolizumab | Experimental | Participants will receive single dose of 800 milligrams (mg) of atezolizumab IV infusion on Day 1, 15 and 29 of Cycle 1 (cycle length=42 days [14-day run-in period + 28-day concomitant dosing period]), thereafter with atezolizumab IV dosing every 2 weeks (q2w) in all subsequent treatment cycles (28 days each). Combination with cobimetinib will begin on Cycle 1 Day 15 and will be given at increasing dose levels during Stage 1. During Stage 1, cobimetinib will be administered once daily (QD) orally for 21 consecutive days out of 28 days (21/7 dosing schedule) at a starting dose of 20 mg with escalation of 20 mg until the maximum tolerated dose (MTD; not more than 60 mg) for the two-drug combination. |
|
| Dose-Expansion: Cobimetinib, Atezolizumab | Experimental | Participants will receive single dose of 800 mg of atezolizumab IV infusion q2w in all subsequent treatment cycles (28 days each). Participants will receive cobimetinib at the selected recommended RP2D on Days 1-14 of each 28-day cycle during Stage 2. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Atezolizumab will be administered at a fixed dose as specified via IV infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase I: Percentage of Participants With Dose-Limiting Toxicities (DLTs) | Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase | |
| Phase I: Maximum Tolerated Dose of Cobimetinib | Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase | |
| Phase I: Recommended Phase II Dose of Cobimetinib when Combined with Atezolizumab | Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Azetolizumab | Pre-infusion (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle length=42 days for Cycle 1; 28 days for subsequent cycles) and at treatment completion visit (up to approximately 3.5 years) | |
| Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) |
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Inclusion Criteria:
Solid tumor that is metastatic, locally advanced or recurrent
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Life expectancy greater than or equal to (>/=) 12 weeks
Measurable disease, as defined by RECIST v 1.1
Adequate hematologic and end organ function
Use of highly effective contraception
Histological tumor tissue specimen
Participants enrolling in the indication-specific expansion cohorts in Stage 2 must consent to tumor biopsies and must have one of the following types of cancer:
Exclusion Criteria:
Cancer-Specific Exclusion Criteria:
General Medical Exclusion Criteria:
Exclusion Criteria Unique to Cobimetinib:
Exclusion Criteria Related to Medications:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Stanford University Medical Center | Palo Alto | California | 94304 | United States | ||
| Rocky Mountain Cancer Center - Denver |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30918950 | Derived | Hellmann MD, Kim TW, Lee CB, Goh BC, Miller WH Jr, Oh DY, Jamal R, Chee CE, Chow LQM, Gainor JF, Desai J, Solomon BJ, Das Thakur M, Pitcher B, Foster P, Hernandez G, Wongchenko MJ, Cha E, Bang YJ, Siu LL, Bendell J. Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors. Ann Oncol. 2019 Jul 1;30(7):1134-1142. doi: 10.1093/annonc/mdz113. |
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|
| Cobimetinib | Drug | Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2. |
|
|
| Baseline up to approximately 3.5 years |
| Serum Maximum Concentration (Cmax) of Atezolizumab | Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years); 30 minutes post-infusion (duration=60 minutes) on Cycle 1 Day 1 (cycle length=42 days) |
| Serum Minimum Concentration (Cmin) of Atezolizumab | Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years) |
| Plasma Cmax of Cobimetinib | Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days) |
| Plasma Cmin of Cobimetinib | Pre-dose (Hour 0) on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days) |
| Area Under the Concentration-Time Curve (AUC) of Cobimetinib | Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days) |
| Percentage of Participants With Best Overall Response, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 of Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until progressive disease [PD] or death due to any cause, whichever occurs first [up to approximately 3.5 years]) | Baseline up to 3.5 years (detailed time frame is provided in the description) |
| Percentage of Participants With Objective Response (OR; Confirmed Complete Response or Partial Response) as Assessed by Investigator Using RECIST v1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years]) |
| Duration of OR, as Determined by Investigator Using RECIST v1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years]) |
| Progression-Free Survival (PFS), as Determined by Investigator Using RECIST v1.1 | Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years]) |
| Overall Survival (OS) | Baseline up to death due to any cause (up to approximately 3.5 years) |
| Denver |
| Colorado |
| 80220 |
| United States |
| Yale University School Of Medicine | New Haven | Connecticut | 06510 | United States |
| Massachusets General Hospital Clinical Trial Network and Institute | Boston | Massachusetts | 02114 | United States |
| Beth Israel Deaconess Med Ctr; Neurology/MS Center | Boston | Massachusetts | 02215 | United States |
| Sloan Kettering Cancer Center; Pediatric Hematology/Oncology | New York | New York | 10065 | United States |
| UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | 27514 | United States |
| Compass Oncology | Portland | Oregon | 97225 | United States |
| SCRI-Tennessee Oncology | Nashville | Tennessee | 37203 | United States |
| Texas Oncology, P.A. | Arlington | Texas | 76012 | United States |
| University of Washington Seattle Cancer Care Alliance | Seattle | Washington | 98195 | United States |
| Peter MacCallum Cancer Centre-East Melbourne | Melbourne | Victoria | 3000 | Australia |
| Royal Melbourne Hospital | Parkville | Victoria | 3050 | Australia |
| Princess Margaret Hospital; Department of Med Oncology | Toronto | Ontario | M5G 2M9 | Canada |
| CHUM Hôpital Notre-Dame | Montreal | Quebec | H2L 4M1 | Canada |
| Jewish General Hospital | Montreal | Quebec | H3T 1E2 | Canada |
| Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden | Dresden | 01307 | Germany |
| Universitaetsklinikum Freiburg | Freiburg im Breisgau | 79106 | Germany |
| National University Hospital; Cancer Center | Singapore | 119074 | Singapore |
| Seoul National University Hospital | Seoul | 03080 | South Korea |
| Asan Medical Center - Oncology | Seoul | 05505 | South Korea |
| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| C574276 | cobimetinib |
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