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

Conditions: Colorectal Cancer; Non-Small Cell Lung Cancer

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.


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.