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Completed

NCT Number: NCT05954871

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

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.

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

GDC-1971

Drug

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

Other names: RO7517834, RLY-1971

Osimertinib

Drug

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

Cetuximab

Drug

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

Primary outcomes

  1. 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

  2. Number of Participants with Dose-Limiting Toxicities (DLTs)

    Time frame: Day 1 through Day 28 of Cycle 1 (1cycle= 28 days)

Secondary outcomes

  1. Plasma Concentration of GDC-1971

    Time frame: Up to approximately 41 months

  2. Plasma Concentration of Osimertinib

    Time frame: Up to approximately 41 months

  3. 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

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

    Time frame: Up to approximately 41 months

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

    Time frame: Up to approximately 41 months

Sponsors and collaborators

Lead sponsor

Genentech, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Jul 20, 2023
Registry last updated
Nov 13, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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