Description:
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.
Title
- Brief Title: A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors
- Official Title: A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0919 Administered With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
GO29779
- SECONDARY ID:
2015-001741-88
- NCT ID:
NCT02471846
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| Atezolizumab | Tecentriq, MPDL3280A, RO5541267 | Anti-PD-1/PD-L1 Relapsed Cohort I |
| GDC-0919 | | Anti-PD-1/PD-L1 Relapsed Cohort I |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Anti-PD-1/PD-L1 Relapsed Cohort I | Experimental | 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 | Experimental | 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 A | Experimental | 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. | |
| Biopsy Cohort B | Experimental | 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. | |
| Dose-Escalation Cohort(s) | Experimental | 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. | |
| Expansion Cohorts | Experimental | 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. | |
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Percentage of Participants With Dose-limiting Toxicities (DLTs) |
| Time Frame: | From Day -1 to 21 of Cycle 1 (each cycle is 21 days) |
| Safety Issue: | |
| Description: | |
Secondary Outcome Measures
| Measure: | Maximum Tolerated Dose (MTD) of GDC-0919 |
| Time Frame: | From Day -1 to 21 of Cycle 1 (each cycle is 21 days) |
| Safety Issue: | |
| Description: | |
| Measure: | Recommended Phase II Dose (RP2D) for GDC-0919 |
| Time Frame: | From Day -1 to 21 of Cycle 1 (each cycle is 21 days) |
| Safety Issue: | |
| Description: | |
| Measure: | Number of Treatment Cycles Received With GDC-0919 and Atezolizumab |
| Time Frame: | From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Dose Intensity of GDC-0919 and Atezolizumab |
| Time Frame: | From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Plasma Maximum Concentration (Cmax) of GDC-0919 |
| Time Frame: | Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2 |
| Safety Issue: | |
| Description: | |
| Measure: | Plasma Minimum Concentration (Cmin) of GDC-0919 |
| Time Frame: | Pre-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8 |
| Safety Issue: | |
| Description: | |
| Measure: | Area Under the Concentration-time Curve to the Last Measurable Concentration (AUC0-last) of GDC-0919 |
| Time Frame: | Pre-dose and post-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8 |
| Safety Issue: | |
| Description: | |
| Measure: | Time to Maximum Concentration (Tmax) of GDC-0919 |
| Time Frame: | Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2 |
| Safety Issue: | |
| Description: | |
| Measure: | Serum Cmax of Atezolizumab |
| Time Frame: | 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) |
| Safety Issue: | |
| Description: | |
| Measure: | Serum Cmin of Atezolizumab |
| Time Frame: | Pre-dose from Day 1 of Cycle 1 up to 120 days after last dose of atezolizumab (up to approximately 3 years) |
| Safety Issue: | |
| Description: | |
| Measure: | 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 |
| Time Frame: | From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Objective Response According to RECIST v1.1 as Determined by the Investigator |
| Time Frame: | From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Percentage of Participants With Objective Response According to Modified RECIST as Determined by the Sponsor |
| Time Frame: | From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Objective Response According to Modified RECIST as Determined by the Sponsor |
| Time Frame: | From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Genentech, Inc. |
Last Updated
October 22, 2019
