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

NCT05954871 | Completed Phase 1 FDA Drug

• 2 other identifiers: GO442722022-502530-10-00
• Study Type: interventional
• Target: 10
• Locations: 3 countries
• Sites: 6

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.

Conditions

Colorectal Cancer; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants with Adverse Events (AEs) Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0

  Up to approximately 41 months

• Number of Participants with Dose-Limiting Toxicities (DLTs)

  Day 1 through Day 28 of Cycle 1 (1cycle= 28 days)

Secondary Outcomes (5)

• Plasma Concentration of GDC-1971

  Up to approximately 41 months

• Plasma Concentration of Osimertinib

  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).

  Up to approximately 41 months

• Duration of Response (DOR) as Determined by Investigator According to RECIST v1.1

  Up to approximately 41 months

• Progression-Free Survival (PFS) After Enrollment as Determined by Investigator According to RECIST v1.1

  Up to approximately 41 months

Study Arms (4)

Dose-Finding Stage: Non-Small Cell Lung Cancer (NSCLC)

EXPERIMENTAL

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.

Drug: GDC-1971; Drug: Osimertinib

Dose-Finding Stage: Colorectal Cancer (CRC)

EXPERIMENTAL

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.

Drug: GDC-1971; Drug: Cetuximab

Dose Expansion Stage: NSCLC

EXPERIMENTAL

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.

Drug: GDC-1971; Drug: Osimertinib

Dose Expansion Stage: CRC

EXPERIMENTAL

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.

Drug: GDC-1971; Drug: Cetuximab

Interventions

GDC-1971 DRUG

GDC-1971 capsules or tablets will be administered as specified in each treatment arm.

Also known as: RO7517834, RLY-1971

Dose Expansion Stage: CRC; Dose Expansion Stage: NSCLC; Dose-Finding Stage: Colorectal Cancer (CRC); Dose-Finding Stage: Non-Small Cell Lung Cancer (NSCLC)

Osimertinib DRUG

Osimertinib tablets will be administered as specified in each treatment arm.

Dose Expansion Stage: NSCLC; Dose-Finding Stage: Non-Small Cell Lung Cancer (NSCLC)

Cetuximab DRUG

Cetuximab, solution for infusion will be administered as specified in each treatment arm.

Dose Expansion Stage: CRC; Dose-Finding Stage: Colorectal Cancer (CRC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Evaluable or measurable disease per RECIST v1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of ≥12 weeks
• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (6)

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

START South Texas Accelerated Research Therapeutics-San Antonio

San Antonio, Texas, 78229, United States

Location

Border Medical Oncology

Wodonga, New South Wales, 3690, Australia

Location

St Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib; Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2023
• First Posted: July 20, 2023
• Study Start: January 8, 2024
• Primary Completion: September 16, 2025
• Study Completion: September 16, 2025
• Last Updated: November 13, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share

Locations

KR (2); US (2); AU (2)