A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors
- Registration Number
- NCT02471846
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of GDC-0919 and atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy or for which standard therapy is ineffective, intolerable, or inappropriate. Participants will be enrolled in two stages, including a dose-escalation stage and an expansion stage.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 158
Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Life expectancy at least 12 weeks
- Adequate hematologic and end organ function
- Negative pregnancy test and willingness to utilize contraception among women of childbearing potential
- Locally advanced, recurrent, or metastatic incurable solid malignancy with measurable disease per RECIST v1.1
- Progression following at least one standard therapy; or standard therapy considered ineffective, intolerable, or inappropriate; or use of an investigational agent recognized as a standard of care
- For the expansion stage, histologically confirmed renal cell cancer (RCC), urothelial bladder cancer (UBC), triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), melanoma, head and neck squamous cell carcinoma (HNSCC), gastric cancer, ovarian cancer, cervical cancer, endometrial cancer, or Merkel cell cancer
- For the expansion stage, evaluable for PD-L1 expression
- Anti PD-1/PD-L1 relapsed cohorts (I and II), participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade will be enrolled
Exclusion Criteria
- Significant cardiovascular or liver disease
- Major surgery within 28 days of study drug
- Any anti-cancer therapy within 3 weeks of study drug
- Malabsorption syndrome or poor upper gastrointestinal integrity
- Primary central nervous system (CNS) malignancy or active metastases within 5 years
- Uncontrolled tumor pain
- Autoimmune disease other than stable hypothyroidism or vitiligo
- Human immunodeficiency virus (HIV), active hepatitis B or C, or tuberculosis
- Signs/symptoms of infection, or use of antibiotics within 2 weeks of study drug
- Live attenuated vaccine within 4 weeks of study drug
- Known history or predisposition to QT interval prolongation
- Prior cancer immunotherapy, specifically indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO) inhibitors, T-cell costimulatory receptor agonist antibodies, or checkpoint inhibitors among certain participants
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Anti-PD-1/PD-L1 Relapsed Cohort II Atezolizumab Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade and achieved unconfirmed partial response or stable disease will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Biopsy Cohort B Atezolizumab Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive atezolizumab during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Anti-PD-1/PD-L1 Relapsed Cohort I GDC-0919 Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade and achieved best response of confirmed complete or partial response, or stable disease will receive GDC-0919, at the MTD or maximum administered dose (MAD) determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Anti-PD-1/PD-L1 Relapsed Cohort II GDC-0919 Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade and achieved unconfirmed partial response or stable disease will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Biopsy Cohort B GDC-0919 Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive atezolizumab during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Expansion Cohorts GDC-0919 Approximately 160 participants (40 per diagnosis) with NSCLC, RCC, TNBC, and UBC will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with Atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Dose-Escalation Cohort(s) GDC-0919 Approximately 6 to 65 participants will be enrolled and treated at escalating doses of GDC-0919 in combination with fixed-dose atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Successive groups of at least 3 participants will be evaluated during a 21-day window for DLTs, which will determine the enrollment and dosing for subsequent cohorts in the dose-escalation stage. The MTD or MAD, whichever is reached first, will be considered for the expansion stage. Biopsy Cohort A GDC-0919 Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive GDC-0919 during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Anti-PD-1/PD-L1 Relapsed Cohort I Atezolizumab Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade and achieved best response of confirmed complete or partial response, or stable disease will receive GDC-0919, at the MTD or maximum administered dose (MAD) determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Biopsy Cohort A Atezolizumab Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive GDC-0919 during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Expansion Cohorts Atezolizumab Approximately 160 participants (40 per diagnosis) with NSCLC, RCC, TNBC, and UBC will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with Atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Dose-Escalation Cohort(s) Atezolizumab Approximately 6 to 65 participants will be enrolled and treated at escalating doses of GDC-0919 in combination with fixed-dose atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Successive groups of at least 3 participants will be evaluated during a 21-day window for DLTs, which will determine the enrollment and dosing for subsequent cohorts in the dose-escalation stage. The MTD or MAD, whichever is reached first, will be considered for the expansion stage.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Dose-limiting Toxicities (DLTs) From Day -1 to 21 of Cycle 1 (each cycle is 21 days) Percentage of Participants With Adverse Events From Screening until new anti-cancer therapy or up to 60 days after last dose (up to approximately 3 years)
- Secondary Outcome Measures
Name Time Method Number of Treatment Cycles Received With GDC-0919 and Atezolizumab From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years) Recommended Phase II Dose (RP2D) for GDC-0919 From Day -1 to 21 of Cycle 1 (each cycle is 21 days) Dose Intensity of GDC-0919 and Atezolizumab From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years) Plasma Minimum Concentration (Cmin) of GDC-0919 Pre-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8 Time to Maximum Concentration (Tmax) of GDC-0919 Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2 Serum Cmax of Atezolizumab Post-dose from Day 1 of Cycle 1 (each cycle is 21 days) up to 120 days after last dose of atezolizumab (up to approximately 3 years) Maximum Tolerated Dose (MTD) of GDC-0919 From Day -1 to 21 of Cycle 1 (each cycle is 21 days) Duration of Objective Response According to RECIST v1.1 as Determined by the Investigator From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) Percentage of Participants With Objective Response According to Modified RECIST as Determined by the Sponsor From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as Determined by the Investigator From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab Pre-dose from Day 1 of Cycle 1 (each cycle is 21 days) up to 120 days after last dose of atezolizumab (up to approximately 3 years) Plasma Maximum Concentration (Cmax) of GDC-0919 Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2 Area Under the Concentration-time Curve to the Last Measurable Concentration (AUC0-last) of GDC-0919 Pre-dose and post-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8 Serum Cmin of Atezolizumab Pre-dose from Day 1 of Cycle 1 up to 120 days after last dose of atezolizumab (up to approximately 3 years) Duration of Objective Response According to Modified RECIST as Determined by the Sponsor From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years)
Trial Locations
- Locations (18)
HonorHealth Research Institute - Bisgrove
🇺🇸Scottsdale, Arizona, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Hopital Nord AP-HM
🇫🇷Marseille, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center - Oncology
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario HM Sanchinarro-CIOCC
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
The Angeles Clinic and Research Institute, Santa Monica Office
🇺🇸Santa Monica, California, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
H. Lee Moffitt Cancer Center and Research Inst.
🇺🇸Tampa, Florida, United States
University of Colorado
🇺🇸Aurora, Colorado, United States