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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-000631-27 | EudraCT Number |
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The study will include a safety run-in phase (Stage 1) and a randomization phase (Stage 2).
The purpose of Stage 1 is to evaluate the safety of cobimetinib when administered in combination with niraparib (Cohort 1) and cobimetinib with niraparib plus atezolizumab (Cohort 2).
Stage 1 will enable patient enrollment in the randomized phase of the study (Stage 2) with both regimens at the recommended dose levels from Stage 1.
Stage 2 is a randomized, dose-expansion phase, evaluating clinical outcomes in patients with advanced platinum-sensitive ovarian cancer.
All patients will continue to receive study treatment until disease progression (according to "Response Evaluation Criteria in Solid Tumors" (RECIST), Version 1.1, unacceptable toxicity, death, or patient or investigator decision to withdraw, whichever occurs first.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Cobimetinib - Niraparib | Experimental | Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib PO QD on Days 1-28 of each 28-day cycle at the established dose for the doublet regimen in Stage 1, Cohort 1. |
|
| Arm B: Cobimetinib - Niraparib - Atezolizumab | Experimental | Stage 2 - Patients will receive cobimetinib PO QD on Days 1-21 (21/7 schedule) in combination with niraparib QD on Days 1-28 at the established doses for the triplet regimen in Stage 1,Cohort 2 plus atezolizumab by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle. |
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| Cohort 1 - Cobimetinib - Niraparib | Experimental | Stage 1 - Patients in Cohort 1 will be treated with cobimetinib plus niraparib. Cobimetinib: Patients will receive a starting dose of 60 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle. Niraparib: Patients will receive a starting dose of 200 mg of niraparib PO QD on Days 1-28 of each 28-day cycle. |
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| Cohort 2 - Cobimetinib - Niraparib - Atezolizumab | Experimental | Stage 1 - Patients in Cohort 2 will be treated with cobimetinib plus niraparib and atezolizumab. Cobimetinib: Patients will receive a starting dose of 60 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle. Niraparib: Patients will receive a starting dose of 200 mg of niraparib PO QD on Days 1-28 of each 28-day cycle. Atezolizumab: Patients will also receive atezolizumab administered as an IV infusion at a fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cobimetinib | Drug | Cobimetinib will be administered at a starting dose of 60 mg by mouth (PO) daily (QD) on Days 1-21 of each 28-day cycle (Stage 1) and PO QD on Days 1-21 (21/7 schedule) at the established dose for the doublet regimen in Stage 1 (Stage 2). |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients reporting Adverse Events (AEs) | The safety profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of number of patients reporting serious and non-serious AEs with severity graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI - CTCAE v5.0) | From baseline up to 48 months |
| Change from baseline in targeted clinical laboratory test results | The safety profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumabwill be evaluated in terms of number of patients reporting change from baseline in targeted clinical laboratory test results. | From baseline up to 48 months |
| Investigator-assessed confirmed objective response rate (ORR) | The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of investigator-assessed confirmed ORR, as determined using RECIST v1.1 in the Intention To Treat (ITT) population and in molecularly defined subgroups by loss of heterozygosity (LOH) status. | From baseline up to 48 months |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free survival (PFS) | The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first, in the ITT population and in the molecularly defined subgroups by LOH status. |
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Inclusion Criteria
Exclusion Criteria
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arizona Cancer Center, North | Tucson | Arizona | 85719 | United States | ||
| Moores Cancer Center at UC San Diego Health |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38288862 | Derived | Mutch D, Voulgari A, Chen XM, Bradley WH, Oaknin A, Perez Fidalgo JA, Montosa FG, Herraez AC, Holloway RW, Powell MA, Nowicka M, Schaefer G, Merchant M, Yan Y. Primary results and characterization of patients with exceptional outcomes in a phase 1b study combining PARP and MEK inhibition, with or without anti-PD-L1, for BRCA wild-type, platinum-sensitive, recurrent ovarian cancer. Cancer. 2024 Jun 1;130(11):1940-1951. doi: 10.1002/cncr.35222. Epub 2024 Jan 30. |
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Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
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| Niraparib | Drug | Niraparib will be administered at a starting dose of 200 mg of niraparib PO QD on Days 1-28 of each 28-day cycle (Stage 1) and PO QD on Days 1-28 of each 28-day cycle at the established dose for the doublet regimen in Stage 1 (Stage 2). |
|
| Atezolizumab | Drug | Atezolizumab will be administered by IV infusion at the fixed dose of 840 mg on Days 1 and 15 (+/-3 days) of each 28-day cycle (Stages 1 and 2). |
|
| From Baseline up to 48 months |
| Duration of response (DOR) | The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of DOR, defined for patients achieving at least one confirmed Partial Response (PR), which is measured from the first observation of a Complete Response (CR) or a PR to the time of disease progression in the ITT population and in the molecularly defined subgroups by LOH status. | From baseline up to 48 months |
| Overall survival (OS) | The efficacy profiles of Cobimetinib plus Niraparib and Cobimetinib plus Niraparib plus Atezolizumab will be evaluated in terms of OS after randomization, defined as the time from randomization until death from any cause in the ITT population and in the molecularly defined subgroups by LOH status. | From baseline up to 48 months |
| Plasma concentration of cobimetinib and niraparib | The Pharmacokinetic (PK) profile of cobimetinib plus niraparib is evaluated in terms of Plasma concentration at specified timepoints. | Arm A: Day 15 of Cycle 1 and 2 - Arm B: Day 15 of Cycle 1 |
| Serum concentration of atezolizumab | The PK profile of cobimetinib plus niraparib plus atezolizumab will be evaluated in terms of Serum concentration of atezolizumab at specified timepoints (Arm B only). | Day 1 of Cycle 1, 2 and 3 and at treatment discontinuation visit, up to 48 months |
| Number of patients with Anti-Drug Antibodies (ADA) | The immunogenicity profile of Atezolizumab is evaluated in terms of number of patients with ADA at baseline and during the study. | Day 1 of Cycle 1, 2 and 3 and at treatment discontinuation visit, up to 48 months |
| La Jolla |
| California |
| 92093 |
| United States |
| Mayo Clinic-Jacksonville | Jacksonville | Florida | 32224 | United States |
| Florida Hospital Cancer Institute; Clinical Research Department | Orlando | Florida | 32804 | United States |
| Medical College of Georgia; Obstetrics & Gynecolog | Augusta | Georgia | 30912-3335 | United States |
| Washington University School of Medicine; Dept of Medicine/Div of Medical Oncology | St Louis | Missouri | 63108 | United States |
| Stephenson Cancer Center Investigational Pharmacy | Oklahoma City | Oklahoma | 73104 | United States |
| Tennessee Oncology; Sarah Cannon Research Institute | Nashville | Tennessee | 37203 | United States |
| Medical College of Wisconsin; Department of Obstetrics and Gynecology | Milwaukee | Wisconsin | 53226 | United States |
| Istituto Nazionale Tumori Fondazione G. Pascale | Naples | Campania | 80131 | Italy |
| Fondazione Policlinico Universitario "A. Gemelli"; Unità di Fase 1: Unità di Farmacologia Clinica | Rome | Lazio | 00168 | Italy |
| Istituto Europeo di Oncologia; Svil. Nuovi Farmaci per Terapie Innovative | Milan | Lombardy | 20141 | Italy |
| Centro Oncologico de Galicia COG; Medical Oncology | A Coruña | LA Coruña | 15009 | Spain |
| Hospital Universitari Vall dHebron; Oncology | Barcelona | 08035 | Spain |
| ICO Girona | Girona | 17007 | Spain |
| Complejo Hospitalario de Jaen-Hospital Universitario Medico Quirurgico; Servicio de Oncologia | Jaén | 23007 | Spain |
| Clinica Universidad de Navarra Madrid; Servicio de Oncología | Madrid | 28027 | Spain |
| Hospital Ramon y Cajal; Servicio de Oncologia | Madrid | 28034 | Spain |
| Hospital Clinico San Carlos; Servicio de Oncologia | Madrid | 28040 | Spain |
| Hospital Clínico Universitario de Valencia; Servicio de Oncología | Valencia | 46010 | Spain |
| ID | Term |
|---|---|
| D010051 | Ovarian Neoplasms |
| ID | Term |
|---|---|
| D004701 | Endocrine Gland Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D000091662 | Genital Diseases |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
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| ID | Term |
|---|---|
| C574276 | cobimetinib |
| C545685 | niraparib |
| C000594389 | atezolizumab |
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