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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors; Metastatic Solid Tumors
• Intervention / Treatment: Drug: GDC-1971; Drug: Atezolizumab; Drug: Omeprazole

• Study Type: Interventional
• Enrollment (Estimated): 232
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: GO43712 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Argentina
  • Cordoba, Argentina, X5000JHQ
    • Recruiting
    • Sanatorio Allende
  • La Rioja, Argentina, F5300COE
    • Recruiting
    • Fundación CORI para la Investigación y Prevención del Cáncer
  • Rosario, Argentina, S2013SBK
    • Recruiting
    • Centro Medico IPAM
• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Recruiting
      • St Vincent'S Hospital Sydney
    • Wodonga, New South Wales, Australia, 3690
      • Recruiting
      • Border Medical Oncology
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Recruiting
      • Flinders Medical Centre
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • One Clinical Research Perth
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
      • Recruiting
      • Santa Casa de Misericordia de Belo Horizonte - PPDS
  • PA
    • Curitiba, PA, Brazil, 81520-060
      • Recruiting
      • Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner
    • Porto Alegre, PA, Brazil, 90035-903
      • Recruiting
      • Hospital de Clinicas de Porto Alegre HCPA PPDS
  • RS
    • Caxias Do Sul, RS, Brazil, 95070-561
      • Recruiting
      • Universidade de Caxias do Sul
    • Ijuí, RS, Brazil, 98700-000
      • Recruiting
      • ONCOSITE Centro de Pesquisa Clínica Em Oncologia
  • SP
    • JAU, SP, Brazil, 17210-080
      • Recruiting
      • Fundação Doutor Amaral Carvalho - Hospital Amaral
    • Sao Jose Do Rio Preto, SP, Brazil, 15090-000
      • Recruiting
      • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS
    • Sao Paulo, SP, Brazil, 01246-000
      • Recruiting
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
    • São Paulo, SP, Brazil, 03102-006
      • Recruiting
      • Instituto Brasileiro de Controle do Cancer Ibcc
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Recruiting
      • Cross Cancer Institute
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 1Z5
      • Recruiting
      • Princess Margaret Cancer Centre
• Korea, Republic of
  • Cheongju si, Korea, Republic of, 28644
    • Recruiting
    • Chungbuk National University Hospital
  • Goyang-si, Korea, Republic of, 10408
    • Recruiting
    • National Cancer Center
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center - PPDS
  • Seoul, Korea, Republic of, 6591
    • Recruiting
    • The Catholic University of Korea Seoul St. Mary?s Hospital
  • Suwon-si, Korea, Republic of, 16247
    • Recruiting
    • The Catholic University Of Korea St. Vincent's Hospital
• New Zealand
  • Auckland, New Zealand, 1124
    • Recruiting
    • Auckland City Hospital
• Poland
  • Pozna?, Poland, 60-335
    • Withdrawn
    • Uniwersytecki Szpital Kliniczny w Poznaniu
• Spain
  • Barcelona, Spain, 08025
    • Withdrawn
    • Hospital de la Santa Creu i Sant Pau
  • Madrid, Spain, 28033
    • Withdrawn
    • MD Anderson Cancer Center Madrid ? Espana
  • Madrid, Spain, 28034
    • Withdrawn
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28036
    • Withdrawn
    • Clinica Universitaria Navarra (Madrid)
  • Sevilla, Spain, 41013
    • Withdrawn
    • Hospital Universitario Virgen del Rocío
  • Sevilla, Spain, 41013
    • Withdrawn
    • Hospital Universitario Virgen Macarena
  • Valencia, Spain, 46010
    • Withdrawn
    • Hospital Clinico Universitario de Valencia
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • Withdrawn
      • NEXT Oncology-Hospital Quironsalud Madrid
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Withdrawn
      • Clinica Universidad de Navarra
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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: RO7517834, RLY-1971; Drug: Atezolizumab; Administered as IV infusion.; Other Names: RO5541267
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: RO7517834, RLY-1971; Drug: Atezolizumab; Administered as IV infusion.; Other Names: RO5541267; Drug: Omeprazole; Administered orally as tablet or capsule in the acid-reducing agent assessment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2022
• Primary Completion (Estimated): May 31, 2025
• Study Completion (Estimated): May 31, 2025

Study Registration Dates

• First Submitted: July 21, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Atezolizumab; Omeprazole
• Other Study ID Numbers: GO43712; 2021-006479-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No