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

• ClinicalTrials.gov Identifier: NCT05487235
• Recruitment Status: Recruiting
• First Posted: August 4, 2022
• Last Update Posted: May 10, 2024
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: July 21, 2022
• First Posted Date: August 4, 2022
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: August 17, 2022
• Estimated Primary Completion Date: May 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 2, 2022)

• Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to approximately 2.5 years ]
• Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: From Day 1 to Day 21 of Cycle 1 of the dose finding stage ]
• Plasma Concentration of GDC-1971 [ Time Frame: Up to approximately 2.5 years ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 2, 2022)

• Area Under the Concentration-Time Curve From Time 0 to 96 hours (AUC0-96 hr) Following GDC-1971 Capsule or Tablet Administration [ Time Frame: Up to approximately 2.5 years ]
• AUC From Time 0 to Infinity (AUCinf) Following GDC-1971 Capsule or Tablet Administration [ Time Frame: Up to approximately 2.5 years ]
• Cmax of GDC-1971 Following Capsule or Tablet Administration [ Time Frame: Up to approximately 2.5 years ]
• AUC 0-96 hr Following GDC-1971 Tablet Administration Under Fasted and Fed Conditions [ Time Frame: Up to approximately 2.5 years ]
• AUC inf Following GDC-1971 Tablet Administration Under Fasted and Fed Conditions [ Time Frame: Up to approximately 2.5 years ]
• Cmax of GDC-1971 Following Tablet Administration Under Fasted and Fed Conditions [ Time Frame: Up to approximately 2.5 years ]
• AUC 0-24 hr at Steady State Following GDC-1971 Tablet Administration and in Combination With Omeprazole [ Time Frame: Up to approximately 2.5 years ]
• Cmax at Steady State Following GDC-1971 Tablet Administration and in Combination With Omeprazole [ Time Frame: Up to approximately 2.5 years ]
• Objective Response Rate (ORR) [ Time Frame: Up to approximately 2.5 years ]
• Duration of Response (DOR) [ Time Frame: Up to approximately 2.5 years ]
• Progression Free Survival (PFS) [ Time Frame: Up to approximately 2.5 years ]
• PFS Rate [ Time Frame: Month 6 ]
• Overall Survival (OS) Rate [ Time Frame: Months 6 and 12 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced Solid Tumors
• Metastatic Solid Tumors

Intervention

• Drug: GDC-1971
  Capsule or tablet administered orally.
  Other Name: RO7517834, RLY-1971
• Drug: Atezolizumab
  Administered as IV infusion.
  Other Name: RO5541267
• Drug: Omeprazole
  Administered orally as tablet or capsule in the acid-reducing agent assessment.

Study Arms

• 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.
  Interventions:

  • Drug: GDC-1971
  • Drug: Atezolizumab
• 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.
  Interventions:

  • Drug: GDC-1971
  • Drug: Atezolizumab
  • Drug: Omeprazole

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 2, 2022): 232
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 31, 2025
• Estimated Primary Completion Date: May 31, 2025 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Argentina, Australia, Brazil, Canada, Korea, Republic of, New Zealand, Poland, Spain, United States

Administrative Information

• NCT Number: NCT05487235
• Other Study ID Numbers: GO43712; 2021-006479-40 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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).
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)

• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Genentech, Inc.
• Verification Date: May 2024