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 Overview
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Brief Summary
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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.

Official Title
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A Phase Ib, Open-Label Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Advanced Solid Tumors, Metastatic Solid Tumors

Intervention / Treatment
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* Drug: GDC-1971
* Drug: Atezolizumab
* Drug: Omeprazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose-finding Stage: GDC-1971<br>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<br>* Capsule or tablet administered orally.<br>* Other names: RO7517834, RLY-1971;Drug: Atezolizumab<br>* Administered as IV infusion.<br>* Other names: RO5541267;|
| Experimental: Expansion Stage: GDC-1971<br>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<br>* Capsule or tablet administered orally.<br>* Other names: RO7517834, RLY-1971;Drug: Atezolizumab<br>* Administered as IV infusion.<br>* Other names: RO5541267;Drug: Omeprazole<br>* Administered orally as tablet or capsule in the acid-reducing agent assessment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |