A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of GDC-1971 when administered in combination with atezolizumab in participants with locally advanced or metastatic solid tumors.
The study will have 2 stages- dose finding stage and expansion stage. In expansion stage participants with non-small cell lung cancer programmed death ligand -1 high (NSCLC PD L-1 high), NSCLC PD L-1 low, head and neck squamous cell carcinoma (HNSCC) PD L-1 positive, BRAF wild type (BRAF WT) melanoma and any locally advanced or metastatic solid tumors will be enrolled.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose-finding Stage: GDC-1971 Participants will receive GDC-1971 tablet or capsule at assigned dose, orally once daily (QD) on Days 1-21 of each cycle, along with atezolizumab 1200 milligrams (mg) intravenous (IV) infusion once every 3 weeks (Q3W), until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet versus (vs) capsule formulations. |
Drug: GDC-1971
Capsule or tablet administered orally.
Other Names:
Drug: Atezolizumab
Administered as IV infusion.
Other Names:
|
| Experimental: Expansion Stage: GDC-1971 Participants will receive GDC-1971 orally at the assigned dose QD on Days 1-21 of each cycle and atezolizumab 1200 mg IV on Day 1 of each cycle until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet vs capsule formulation, the effect of food and acid-reducing agents on GDC-1971. |
Drug: GDC-1971
Capsule or tablet administered orally.
Other Names:
Drug: Atezolizumab
Administered as IV infusion.
Other Names:
Drug: Omeprazole
Administered orally as tablet or capsule in the acid-reducing agent assessment.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With Adverse Events (AEs) [Up to approximately 2.5 years]
- Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs [Baseline up to 30 days after final dose of study treatment (up approximately to 2.5 years)]
- Percentage of Participants With Clinically Significant Change from Baseline in Clinical Laboratory Test Results [Baseline up to 30 days after final dose of study treatment (up approximately to 2.5 years)]
- Percentage of Participants With Clinically Significant Change From Baseline in RR and QT Intervals as Measured by Electrocardiogram (ECG) [Baseline up to 30 days after final dose of study treatment (up approximately to 2.5 years)]
- Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) [From Day 1 to Day 21 of Cycle 1 of the dose finding stage]
- Plasma Concentration of GDC-1971 [Up to approximately 2.5 years]
Secondary Outcome Measures
- Area Under the Concentration-Time Curve From Time 0 to 96 hours (AUC0-96 hr) Following GDC-1971 Capsule or Tablet Administration [Up to approximately 2.5 years]
- AUC From Time 0 to Infinity (AUCinf) Following GDC-1971 Capsule or Tablet Administration [Up to approximately 2.5 years]
- Cmax of GDC-1971 Following Capsule or Tablet Administration [Up to approximately 2.5 years]
- AUC 0-96 hr Following GDC-1971 Tablet Administration Under Fasted and Fed Conditions [Up to approximately 2.5 years]
- AUC inf Following GDC-1971 Tablet Administration Under Fasted and Fed Conditions [Up to approximately 2.5 years]
- Cmax of GDC-1971 Following Tablet Administration Under Fasted and Fed Conditions [Up to approximately 2.5 years]
- AUC 0-24 hr at Steady State Following GDC-1971 Tablet Administration and in Combination With Omeprazole [Up to approximately 2.5 years]
- Cmax at Steady State Following GDC-1971 Tablet Administration and in Combination With Omeprazole [Up to approximately 2.5 years]
- Objective Response Rate (ORR) [Up to approximately 2.5 years]
- Duration of Response (DOR) [Up to approximately 2.5 years]
- Progression Free Survival (PFS) [Up to approximately 2.5 years]
- PFS Rate [Month 6]
- Overall Survival (OS) Rate [Months 6 and 12]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has Eastern Cooperative Oncology Group(ECOG) Performance Status of 0 or 1
-
Has Life expectancy >= 12 weeks
-
Adequate organ function
-
Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).
Inclusion Criteria for Dose-Finding Stage:
- Histologically confirmed locally advanced or metastatic solid tumor that has progressed after at least one available standard therapy or for which approved standard therapy has proven to be ineffective or intolerable
Inclusion Criteria for Expansion Stage: NSCLC Cohort
-
Histologically confirmed locally advanced or metastatic NSCLC
-
Absence of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)
-
PD- L1 positive
-
No prior systemic therapy for locally advanced or metastatic NSCLC
Inclusion Criteria for Expansion Stage: HNSCC Cohort
-
Histologically confirmed recurrent, or metastatic HNSCC
-
PD-L1 positive
-
No prior systemic therapy for recurrent or metastatic HNSCC
Inclusion Criteria for Expansion Stage: BRAF WT melanoma Cohort
- Histologically confirmed locally advanced or metastatic or unresectable locally advanced cutaneous BRAF WT melanoma or melanomas of unknown primary that are non-mucosal and non -uveal that has progressed on or after treatment that included anti PD1 or anti PD-L1 therapy
Inclusion Criteria for Expansion Stage: Other Advanced or Metastatic Solid Tumors Cohort
- Histologically confirmed locally advanced or metastatic solid tumor that has progressed after at least one available standard therapy or for which approved standard therapy has proven to be ineffective or intolerable, standard therapy is considered inappropriate, or an investigational agent is a recognized standard of care
Exclusion Criteria:
-
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
-
Has leptomeningeal disease or carcinomatous meningitis
-
Has uncontrolled hypertension
-
Has left ventricular ejection fraction < institutional lower limit of normal or < 50%
-
Has clinically significant history of liver disease including viral or other hepatitis, current alcohol abuse, or cirrhosis
-
Has an active or history of autoimmune disease or immune deficiency including myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or multiple sclerosis. Participants with a history of autoimmune- related hypothyroidism on thyroid replacement hormone or with controlled Type I diabetes mellitus on a stable dose of an insulin regimen are eligible for this study
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | City of Hope | Duarte | California | United States | 91010 |
| 2 | Chungbuk National University Hospital | Cheongju-si | Korea, Republic of | 28644 |
Sponsors and Collaborators
- Genentech, Inc.
Investigators
- Study Director: Clinical Trials, Hoffmann-La Roche
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GO43712
- 2021-006479-40