ClinicalTrials.gov

History of Changes for Study: NCT03312530
A Study of Cobimetinib Administered as Single Agent and in Combination With Venetoclax, With or Without Atezolizumab, in Participants With Relapsed and Refractory Multiple Myeloma
Latest version (submitted August 5, 2021) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 October 12, 2017 None (earliest Version on record)
2 November 2, 2017 Recruitment Status, Contacts/Locations and Study Status
3 November 16, 2017 Contacts/Locations and Study Status
4 November 22, 2017 Study Status and Contacts/Locations
5 May 10, 2018 Contacts/Locations and Study Status
6 July 24, 2018 Study Status and Contacts/Locations
7 October 22, 2018 Contacts/Locations and Study Status
8 December 13, 2018 Study Status
9 January 10, 2019 Study Status
10 February 4, 2019 Contacts/Locations and Study Status
11 February 28, 2019 Study Status and Contacts/Locations
12 April 24, 2019 Study Status
13 June 3, 2019 Study Status and Contacts/Locations
14 July 3, 2019 Study Status and Contacts/Locations
15 August 2, 2019 Recruitment Status, Study Status and Contacts/Locations
16 October 28, 2019 Study Status and Contacts/Locations
17 January 23, 2020 Study Status
18 April 21, 2020 Study Status
19 July 17, 2020 Study Status
20 October 13, 2020 Study Status
21 January 11, 2021 Study Status
22 April 8, 2021 Study Status
23 June 14, 2021 Recruitment Status, Study Status and Study Design
24 August 5, 2021 Study Status
Comparison Format:

Scroll up to access the controls

Study NCT03312530
Submitted Date:  October 12, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: BO39813
Brief Title: A Study of Cobimetinib Administered as Single Agent and in Combination With Venetoclax, With or Without Atezolizumab, in Participants With Relapsed and Refractory Multiple Myeloma
Official Title: A Phase Ib/II Study of Cobimetinib Administered as Single Agent and in Combination With Venetoclax, With or Without Atezolizumab, in Patients With Relapsed and Refractory Multiple Myeloma
Secondary IDs: 2017-000830-68 [EudraCT Number]
Open or close this module Study Status
Record Verification: October 2017
Overall Status: Not yet recruiting
Study Start: November 17, 2017
Primary Completion: October 28, 2020 [Anticipated]
Study Completion: October 28, 2020 [Anticipated]
First Submitted: October 12, 2017
First Submitted that
Met QC Criteria:
October 12, 2017
First Posted: October 17, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
October 12, 2017
Last Update Posted: October 17, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Hoffmann-La Roche
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
Brief Summary: This open-label, randomized, multicenter, triple-arm Phase Ib/II study is designed to assess the efficacy, safety, tolerability, and pharmacokinetics of cobimetinib administered as a single agent (Arm A), cobimetinib plus venetoclax (Arm B), and cobimetinib plus venetoclax plus atezolizumab (Arm C) in participants with relapsed and refractory multiple myeloma. Two successive cohorts will evaluate the safety of cobimetinib plus venetoclax and that of cobimetinib plus venetoclax plus atezolizumab in the selected population during the safety run-in phase of the study. Once the dose levels have demonstrated acceptable safety during this phase, randomization will begin for all treatment arms (Arms A, B, and C).
Detailed Description:
Open or close this module Conditions
Conditions: Multiple Myeloma
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1/Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 5
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 72 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: A: Cobimetinib
Participants will receive the standard single-agent cobimetinib dose of 60 milligrams (mg) (3 tablets of 20 mg each) orally (PO) daily on Days 1-21 of each 28-day cycle until disease progression. Upon progression, participants will be allowed to receive treatment with cobimetinib and atezolizumab at the recommended Phase II dose of cobimetinib 60 mg PO on Days 1-21 plus atezolizumab intravenous (IV) infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment will continue until the participant has disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
Drug: Cobimetinib
Cobimetinib will be administered as per the schedule specified in the respective arm.
Other Names:
  • Cotellic®
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
Experimental: B: Cobimetinib + Venetoclax
Participants will receive cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase. Treatment will continue until the participant has disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
Drug: Cobimetinib
Cobimetinib will be administered as per the schedule specified in the respective arm.
Other Names:
  • Cotellic®
Drug: Venetoclax
Venetoclax will be administered as per the schedule specified in the respective arm.
Other Names:
  • GDC-0199, ABT-199
Experimental: C: Cobimetinib + Venetoclax + Atezolizumab
Participants will receive cobimetinib PO daily on Days 1-21 of each 28-day cycle plus venetoclax PO daily on Days 1-28 of each 28-day cycle, at the dose level identified in the safety run-in phase plus atezolizumab IV infusion at a fixed dose of 840 mg on Day 1 and Day 15 of each 28-day cycle. Treatment will continue until the participant has disease progression, unacceptable toxicity, death, participant or physician decision to withdraw, or pregnancy, whichever occurs first.
Drug: Cobimetinib
Cobimetinib will be administered as per the schedule specified in the respective arm.
Other Names:
  • Cotellic®
Drug: Venetoclax
Venetoclax will be administered as per the schedule specified in the respective arm.
Other Names:
  • GDC-0199, ABT-199
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
Experimental: Safety Run-In: Cobimetinib + Venetoclax
Participants will receive cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses, in 28-day cycles, to identify the dose level with acceptable safety.
Drug: Cobimetinib
Cobimetinib will be administered as per the schedule specified in the respective arm.
Other Names:
  • Cotellic®
Drug: Venetoclax
Venetoclax will be administered as per the schedule specified in the respective arm.
Other Names:
  • GDC-0199, ABT-199
Experimental: Safety Run-In: Cobimetinib + Venetoclax + Atezolizumab
Participants will receive cobimetinib (on Day 1-21) plus venetoclax (on Day 1-28) at escalated doses and atezolizumab (on Day 1 and Day 15) at a fixed dose of 840 mg IV, in 28-day cycles, to identify the dose level with acceptable safety.
Drug: Cobimetinib
Cobimetinib will be administered as per the schedule specified in the respective arm.
Other Names:
  • Cotellic®
Drug: Venetoclax
Venetoclax will be administered as per the schedule specified in the respective arm.
Other Names:
  • GDC-0199, ABT-199
Drug: Atezolizumab
Atezolizumab will be administered as per the schedule specified in the respective arm.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Percentage of Participants With Adverse Events (AEs)
[ Time Frame: Randomization up to end of study (up to approximately 24 months) ]

2. Percentage of Participants With Overall Response as Determined by the Investigator Using International Myeloma Working Group (IMWG) Response Criteria
[ Time Frame: From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to approximately 24 months) ]

Secondary Outcome Measures:
1. Percentage of Participants With Clinical Benefit as Determined by the Investigator Using IMWG Response Criteria
[ Time Frame: From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to approximately 24 months) ]

2. Progression-Free Survival (PFS) as Determined by the Investigator Using IMWG Response Criteria
[ Time Frame: From randomization to the first occurrence of disease progression or relapse or death from any cause, whichever occurs first (up to approximately 24 months) ]

3. Duration of Response as Determined by the Investigator Using IMWG Response Criteria
[ Time Frame: Time from the first observation of partial response (PR) to the time of disease progression (up to approximately 24 months) ]

4. Overall Survival
[ Time Frame: From randomization until death from any cause (up to approximately 24 months) ]

5. Area Under the Plasma Concentration Versus Time Curve (AUC) of Cobimetinib
[ Time Frame: Arm A: 2-4 hours(hrs) post-dose on Day 1 of Cycle 1; predose(within 1 hr),2-4 hrs post-dose on Day 15 of Cycle 1; Arm B and C: 2-4 hrs post-dose on Day 1 of Cycle 1; pre-dose(within 1 hr), 2, 4, 6 hrs post-dose on Day 15 of Cycle 1(cycle length: 28 days) ]

6. Maximum Observed Plasma Concentration (Cmax) of Cobimetinib
[ Time Frame: Arm A: 2-4 hrs post-dose on Day 1 of Cycle 1; predose (within 1 hr), 2-4 hrs post-dose on Day 15 of Cycle 1; Arm B and C: 2-4 hrs post-dose on Day 1 of Cycle 1; pre-dose (within 1 hr), 2, 4, 6 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days) ]

7. Time to Reach Cmax (Tmax) of Cobimetinib
[ Time Frame: Arm A: 2-4 hrs post-dose on Day 1 of Cycle 1; predose (within 1 hr), 2-4 hrs post-dose on Day 15 of Cycle 1; Arm B and C: 2-4 hrs post-dose on Day 1 of Cycle 1; pre-dose (within 1 hr), 2, 4, 6 hrs post-dose on Day 15 of Cycle 1 (cycle length: 28 days) ]

8. AUC of Venetoclax
[ Time Frame: 6 hrs post-dose on Day 1 of Cycle 1; pre-dose (within 1 hr), 2, 4, 6, 8 hrs post-dose on Day 15 of Cycle 1; pre-dose (within 1 hr) on Day 1 of Cycles 2, 3 (cycle length: 28 days) ]

9. Cmax of Venetoclax
[ Time Frame: 6 hrs post-dose on Day 1 of Cycle 1; pre-dose (within 1 hr), 2, 4, 6, 8 hrs post-dose on Day 15 of Cycle 1; pre-dose (within 1 hr) on Day 1 of Cycles 2, 3 (cycle length: 28 days) ]

10. Tmax of Venetoclax
[ Time Frame: 6 hrs post-dose on Day 1 of Cycle 1; pre-dose (within 1 hr), 2, 4, 6, 8 hrs post-dose on Day 15 of Cycle 1; pre-dose (within 1 hr) on Day 1 of Cycles 2, 3 (cycle length: 28 days) ]

11. Cmax of Atezolizumab
[ Time Frame: Pre-infusion (0 hr), 0.5 hr post-infusion (infusion duration: 1 hr) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycle 2, 3 (cycle length: 28 days); at treatment discontinuation visit (up to approximately 24 months) ]

12. Minimum Observed Serum Concentration (Cmin) of Atezolizumab
[ Time Frame: Pre-infusion (0 hr), 0.5 hr post-infusion (infusion duration: 1 hr) on Day 1 of Cycle 1; pre-infusion (0 hr) on Day 1 of Cycle 2, 3 (cycle length: 28 days); at treatment discontinuation visit (up to approximately 24 months) ]

13. Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab
[ Time Frame: Pre-infusion (0 hr) on Day 1 of Cycles 1, 2, 3 (cycle length: 28 days); at treatment discontinuation visit (up to approximately 24 months) ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Life expectancy of at least 12 weeks
  • Documented multiple myeloma
  • Received 3 to 5 prior lines of therapy for multiple myeloma, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD)
  • Achieved a response (minimal response [MR] or better) to at least one prior regimen
  • Documented evidence of progressive disease (as defined by the IMWG criteria) on or after their last prior therapy, or participants who were intolerant to their last prior therapy
  • Toxicities resulting from previous therapy (including peripheral neuropathy) that must be resolved or stabilized to Grade 1

Exclusion Criteria:

  • Anti-myeloma treatment within 14 days or 5 pharmacokinetic (PK) half-lives of the treatment, whichever is longer, before the date of randomization
  • Completion of autologous stem cell transplant within 100 days prior to the date of randomization
  • Prior allogeneic stem cell transplant as well as prior solid organ transplant
  • Spinal cord compression not definitively treated with surgery and/or radiation
  • Prior treatment with MEK inhibitors, B-cell lymphoma-2 (Bcl-2) inhibitors, or immune checkpoint inhibitor therapies including anti-cytotoxic T-lymphocyte associated protein-4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1) or anti-programmed death-ligand 1 (anti-PD-L1)
  • Treatment with systemic immunostimulatory agents within 28 days or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
  • Treatment with systemic immunosuppressive medication within 14 days prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
  • Prior radiation therapy within 14 days prior to study enrollment and/or persistence of radiation-related adverse effects
  • History or evidence of retinal pathology on ophthalmic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
  • Left ventricular ejection fraction (LVEF) below institutional lower limit of normal
  • History of clinically significant cardiovascular dysfunction
  • Any previous venous thromboembolism greater than (>) Grade 3 within 12 months of study enrollment
  • History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins (for participants in Arm C only)
  • History of other malignancy that could affect compliance with the protocol or interpretation of results
  • Active or history of autoimmune disease or immune deficiency
  • History of malabsorption or other condition that would interfere with absorption of study drugs
  • Active tuberculosis
  • Severe infection within 28 days prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Treatment with therapeutic oral or IV antibiotics within 14 days prior to initiation of study treatment
  • Positive test results for hepatitis B (hepatitis B surface antigen [HBsAg] and/or total hepatitis B core antibody [HBcAb]) or hepatitis C virus (HCV) antibody
  • Known history of human immunodeficiency virus (HIV) seropositivity
  • Treatment with a live, attenuated influenza vaccine (e.g., FluMist) within 28 days prior to Cycle 1 Day 1, at any time during the study, and for at least 5 months after the last dose of study drug (for participants in Arm C only)
  • Received strong cytochrome P-3A (CYP3A) inhibitors, moderate CYP3A inhibitors, strong CYP3A inducers, and moderate CYP3A inducers within 7 days prior to the initiation of study treatment
Open or close this module Contacts/Locations
Central Contact Person: Reference Study ID Number: BO39813 www.roche.com/about_roche/roche_worldwide.htm
Telephone: 888-662-6728 (U.S. and Canada)
Email: global-roche-genentech-trials@gene.com
Study Officials: Clinical Trials
Study Director
Hoffmann-La Roche
Locations: Czechia
Fakultni nemocnice Brno; Interni hematoonkologicka klinika
Brno, Czechia, 625 00
Fakultni nemocnice Ostrava; Klinika hematoonkologie
Ostrava, Czechia, 708 52
Univerzita Karlova v Praze a Vseobecna fakultni nemocnice v Praze - 1; Lekarska Fakulta - I
Prague 2, Czechia, 128 08
Denmark
Righospitalet, Hæmatologisk Klinik
København Ø, Denmark, 2100
Odense Universitetshospital
Odense C, Denmark, 5000
France
CHU - Hôtel Dieu hematolgie clinique
Nantes, France, 44093
Hôpital Saint-Louis
Paris, France, 75475
CHU Lyon - Centre Hospitalier Lyon Sud
Pierre-Benite (Lyon), France, 69495
IGR
Villejuif, France, 94800
Germany
UNI-Klinikum Heidelberg Medizinische Klinik Innere Medizin V
Heidelberg, Germany, 69120
Uni. der Johannes Gutenberg-Universitaet Mainz; III. Medizinische Klinik und Poliklinik
Mainz, Germany, 55131
Universitätsklinikum Tübingen Medizinische UNI-Klinik und Poliklinik Abt. Innere Medizin II
Tübingen, Germany, 72076
Universitätsklinikum Ulm; Innere Medizin, Klinik für Innere Medizin III
Ulm, Germany, 89081
Netherlands
Academisch Medisch Centrum
Amsterdam, Netherlands, 1105 AZ
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands, 3584 CX
Norway
Førde sentralsjukehus
Førde, Norway, 6800
Oslo University Hospital HF, Rikshospitalet
Oslo, Norway, 0424
Poland
Uniwersytet Medyczny im.Karola Marcinkowskiego w Poznaniu
Poznań, Poland, 60-569
Centrum Onkologii - Inst.Im. Marii Sklodowskiej-Curie; Oncology
Warszawa, Poland, 02-781
Gornoslaskie Centrum Medyczne
Wrocław, Poland, 50-367
Spain
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital Universitario de la Princesa
Madrid, Spain, 28006
Hospital Univ 12 de Octubre
Madrid, Spain, 28041
Spain, Barcelona
Hospital Universitari Germans Trias i Pujol; Servicio de Hematologia
Badalona, Barcelona, Spain, 08915
Spain, Navarra
Clínica Universidad de Navarra
Pamplona, Navarra, Spain, 31620
Sweden
Sahlgrenska University Hospital
Göteborg, Sweden, 413 45
Skånes Universitetssjukhus, Lund
Lund, Sweden, 221 85
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services