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 Met

• Status: Recruiting
• Trial end date: 2026-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Genentech, Inc.
• Treatments: Cetuximab; Osimertinib

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.