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

Genentech

Status and phase: Active, not recruiting; Phase 1

Conditions: Non-Small Cell Lung Cancer; Colorectal Cancer

Treatments: Drug: GDC-1971; Drug: Osimertinib; Drug: Cetuximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05954871

GO44272

2022-502530-10-00 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 172 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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172 participants in 4 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Osimertinib

Drug: GDC-1971

Dose-Finding Stage: Colorectal Cancer (CRC)

Experimental group

Description:

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.

Treatment:

Drug: Cetuximab

Drug: GDC-1971

Dose Expansion Stage: NSCLC

Experimental group

Description:

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.

Treatment:

Drug: Osimertinib

Drug: GDC-1971

Dose Expansion Stage: CRC

Experimental group

Description:

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.

Treatment:

Drug: Cetuximab

Drug: GDC-1971