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

GO44272

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.

2024-01-08

2026-12-31

2026-12-31

Recruiting

Early phase I

172

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 172, 'type': 'ESTIMATED'}}

2024-05-01