Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Either Osimertinib in Participants With Unresectable, Locally Advanced, or Metastatic Non-Small Cell Lung Cancer, or With Cetuximab in Participants With Metastatic Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT05954871
• Recruitment Status: Recruiting
• First Posted: July 20, 2023
• Last Update Posted: May 1, 2024
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: July 12, 2023
• First Posted Date: July 20, 2023
• Last Update Posted Date: May 1, 2024
• Actual Study Start Date: January 8, 2024
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 12, 2023)

• Percentage of Participants with Adverse Events (AEs) Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 [ Time Frame: Up to approximately 41 months ]
• Number of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Day 1 through Day 28 of Cycle 1 (1cycle= 28 days) ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 12, 2023)

• Plasma Concentration of GDC-1971 [ Time Frame: Up to approximately 41 months ]
• Plasma Concentration of Osimertinib [ Time Frame: Up to approximately 41 months ]
• Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). [ Time Frame: Up to approximately 41 months ]
• Duration of Response (DOR) as Determined by Investigator According to RECIST v1.1 [ Time Frame: Up to approximately 41 months ]
• Progression-Free Survival (PFS) After Enrollment as Determined by Investigator According to RECIST v1.1 [ Time Frame: Up to approximately 41 months ]

• 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: Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Either Osimertinib in Participants With Unresectable, Locally Advanced, or Metastatic Non-Small Cell Lung Cancer, or With Cetuximab in Participants With Metastatic Colorectal Cancer
• Official Title: A Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Either Osimertinib in Patients With Unresectable, Locally Advanced, or Metastatic Non-Small Cell Lung Cancer, or With Cetuximab in Patients With Metastatic Colorectal Cancer
• Brief Summary: The main purpose of the study is to evaluate the safety of GDC-1971 in combination with either osimertinib or cetuximab. The study consists of a dose-finding stage followed by an expansion stage.
• 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

• Colorectal Cancer
• Non-Small Cell Lung Cancer

Intervention

• Drug: GDC-1971
  GDC-1971 capsules or tablets will be administered as specified in each treatment arm.
  Other Name: RO7517834, RLY-1971
• Drug: Osimertinib
  Osimertinib tablets will be administered as specified in each treatment arm.
• Drug: Cetuximab
  Cetuximab, solution for infusion will be administered as specified in each treatment arm.

Study Arms

• Experimental: Dose-Finding Stage: Non-Small Cell Lung Cancer (NSCLC)
  Participants with unresectable, locally advanced or metastatic NSCLC will receive GDC-1971 at an assigned dose, orally, once daily (QD), on Days 1 to 28 of each 28-day cycle in combination with osimertinib, 80 milligrams (mg), orally, QD, on Days 1 to 28 of each cycle until disease progression or unacceptable toxicity.
  Interventions:

  • Drug: GDC-1971
  • Drug: Osimertinib
• Experimental: Dose-Finding Stage: Colorectal Cancer (CRC)
  Participants with metastatic CRC will receive GDC-1971, at an assigned dose, orally, QD, on Days 1 to 28 days of each 28-day cycle in combination with cetuximab, 500 milligrams per square meter (mg/m^2), given by IV infusion on Days 1 and 15 of each cycle, until disease progression or unacceptable toxicity.
  Interventions:

  • Drug: GDC-1971
  • Drug: Cetuximab
• Experimental: Dose Expansion Stage: NSCLC
  Participants with unresectable, locally advanced or metastatic NSCLC will receive GDC-1971 at a dose determined in the dose finding stage, orally, QD, on Days 1 to 28 of each 28-day cycle in combination with osimertinib, 80 mg, orally, QD, on Days 1 to 28 of each cycle until disease progression or unacceptable toxicity.
  Interventions:

  • Drug: GDC-1971
  • Drug: Osimertinib
• Experimental: Dose Expansion Stage: CRC
  Participants with metastatic CRC will receive GDC-1971 at a dose determined in the dose finding stage, orally, QD, on Days 1 to 28 of each 28-day cycle in combination with cetuximab, 500 mg/m^2, given by IV infusion on Days 1 and 15 of each cycle until disease progression or unacceptable toxicity.
  Interventions:

  • Drug: GDC-1971
  • Drug: Cetuximab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 12, 2023): 172
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2026
• Estimated Primary Completion Date: December 31, 2026 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Evaluable or measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of ≥12 weeks
• Adequate hematologic and organ function within 14 days prior to initiation of study Inclusion Criteria for Non-Small Cell Lung Cancer Cohorts
• Histologically confirmed unresectable, locally advanced or metastatic adenocarcinoma of the lung that has progressed on/after prior treatment with third-generation epidermal growth factor receptor (EGFR) inhibitor (e.g., osimertinib)
• Positive for an EGFR exon 19 deletion or exon 21 L858R mutation
• Negative for acquired on-target EGFR alterations Inclusion Criteria for Colorectal Cancer Cohorts
• Histologically confirmed metastatic adenocarcinoma of the colon or rectum that has progressed on/after prior treatment with an EGFR inhibitor (e.g., cetuximab or panitumumab)
• Negative for kirsten rat sarcoma viral oncogene homolog (KRAS) alterations
• Negative for neuroblastoma RAS viral oncogene homolog (NRAS) alterations
• Negative for proto-oncogene B-Raf (BRAF) V600E alterations
• In lieu of a fresh pre-treatment biopsy, a recently obtained biopsy performed after completion of osimertinib therapy will be acceptable

Exclusion Criteria:

• Treatment with chemotherapy, immunotherapy, biologic therapy, or an investigational agent as anti-cancer therapy within 3 weeks or 5 drug elimination half-lives, whichever is shorter, prior to initiation of study treatment
• Treatment with endocrine therapy within 2 weeks prior to initiation of study drug, except for hormonal therapy with gonadotropin-releasing hormone agonists or antagonists for endocrine-sensitive cancers
• Significant traumatic injury or major surgical procedure within 4 weeks prior to Cycle 1, Day 1
• Positive hepatitis C virus (HCV) antibody test at screening
• Positive hepatitis B surface antigen (HBsAg) test at screening
• Known HIV infection
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Uncontrolled hypercalcemia
• Substance abuse, as determined by the investigator, within 12 months prior to screening
• Poor peripheral venous access
• Inability or unwillingness to swallow pills
• Malabsorption syndrome or other condition that would interfere with enteral absorption Chronic diarrhea, short bowel syndrome, or significant upper GI surgery including gastric resection, a history of inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), or any active bowel inflammation (including diverticulitis)
• Serious infection within 4 weeks prior to screening
• History of malignancy within 3 years prior to screening
• Known and untreated, or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control)
• Leptomeningeal disease or carcinomatous meningitis
• History or presence of an abnormal electrocardiogram (ECG) that is deemed clinically significant by the investigator (e.g., complete left bundle branch block, second- or third-degree atrioventricular heart block) or evidence of prior myocardial infarction
• Left ventricular ejection fraction (LVEF) less than the institutional lower limit of normal (LLN) or <50%
• History or evidence of ophthalmic disease
• History of or active clinically significant cardiovascular dysfunction
• History of pulmonary firbrosis, organizing pneumonia, or pneumonitis

Other protocol-defined inclusion/exclusion criteria may apply.

Sex/Gender

• Sexes Eligible for Study: All

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

Contacts

Contact: Reference Study ID Number: GO44272 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

• Listed Location Countries: Australia, Canada, Korea, Republic of, United States

Administrative Information

• NCT Number: NCT05954871
• Other Study ID Numbers: GO44272; 2022-502530-10-00 ( Other Identifier: EU Clinical Trial 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).

• 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: April 2024