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

Colorectal Cancer Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05954871
• Other study ID #: GO44272
• Secondary ID: 2022-502530-10-0
• Status: Recruiting
• Phase: Phase 1
• Start date: January 8, 2024
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: Genentech, Inc.
• Contact: Reference Study ID Number: GO44272 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 172
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Colorectal Neoplasms
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• GDC-1971
GDC-1971 capsules or tablets will be administered as specified in each treatment arm.
• Osimertinib
Osimertinib tablets will be administered as specified in each treatment arm.
• Cetuximab
Cetuximab, solution for infusion will be administered as specified in each treatment arm.

Locations

Country	Name	City	State
Australia	St Vincent's Hospital Melbourne	Fitzroy	Victoria
Australia	Border Medical Oncology	Wodonga	New South Wales
Australia	The Queen Elizabeth Hospital	Woodville	South Australia
Canada	Ottawa Hospital	Ottawa	Ontario
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
United States	SCRI Oncology Partners	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Christiana Care Health System	Newark	Delaware
United States	START South Texas Accelerated Research Therapeutics-San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with Adverse Events (AEs) Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0		Up to approximately 41 months
Primary	Number of Participants with Dose-Limiting Toxicities (DLTs)		Day 1 through Day 28 of Cycle 1 (1cycle= 28 days)
Secondary	Plasma Concentration of GDC-1971		Up to approximately 41 months
Secondary	Plasma Concentration of Osimertinib		Up to approximately 41 months
Secondary	Objective Response Rate (ORR) as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).		Up to approximately 41 months
Secondary	Duration of Response (DOR) as Determined by Investigator According to RECIST v1.1		Up to approximately 41 months
Secondary	Progression-Free Survival (PFS) After Enrollment as Determined by Investigator According to RECIST v1.1		Up to approximately 41 months