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
Overview
- Phase
- Phase 1
- Intervention
- GDC-1971
- Conditions
- Colorectal Cancer
- Sponsor
- Genentech, Inc.
- Enrollment
- 10
- Locations
- 6
- Primary Endpoint
- Percentage of Participants with Adverse Events (AEs) Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
- Status
- Completed
- Last Updated
- 5 months ago
Overview
Brief 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.
Investigators
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
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
Arms & Interventions
Dose-Finding Stage: Non-Small Cell Lung Cancer (NSCLC)
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.
Intervention: GDC-1971
Dose-Finding Stage: Non-Small Cell Lung Cancer (NSCLC)
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.
Intervention: Osimertinib
Dose-Finding Stage: Colorectal Cancer (CRC)
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.
Intervention: GDC-1971
Dose-Finding Stage: Colorectal Cancer (CRC)
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.
Intervention: Cetuximab
Dose Expansion Stage: NSCLC
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.
Intervention: GDC-1971
Dose Expansion Stage: NSCLC
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.
Intervention: Osimertinib
Dose Expansion Stage: CRC
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.
Intervention: GDC-1971
Dose Expansion Stage: CRC
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.
Intervention: Cetuximab
Outcomes
Primary Outcomes
Percentage of Participants with Adverse Events (AEs) Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Time Frame: Up to approximately 41 months
Number of Participants with Dose-Limiting Toxicities (DLTs)
Time Frame: Day 1 through Day 28 of Cycle 1 (1cycle= 28 days)
Secondary Outcomes
- 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)
- Plasma Concentration of GDC-1971(Up to approximately 41 months)
- Plasma Concentration of Osimertinib(Up to approximately 41 months)
- Progression-Free Survival (PFS) After Enrollment as Determined by Investigator According to RECIST v1.1(Up to approximately 41 months)
- Duration of Response (DOR) as Determined by Investigator According to RECIST v1.1(Up to approximately 41 months)