Advanced Solid Tumors, Metastatic Solid Tumors
Conditions
Brief summary
The purpose of this study is to evaluate the safety, pharmacokinetics (PK), and activity of GDC-1971 when administered in combination with atezolizumab in participants with locally advanced or metastatic solid tumors. The study will have 2 stages- dose finding stage and expansion stage. In expansion stage participants with non-small cell lung cancer programmed death ligand -1 high (NSCLC PD L-1 high), NSCLC PD L-1 low, head and neck squamous cell carcinoma (HNSCC) PD L-1 positive, BRAF wild type (BRAF WT) melanoma and any locally advanced or metastatic solid tumors will be enrolled.
Interventions
DRUGGDC-1971
Capsule or tablet administered orally.
DRUGAtezolizumab
Administered as IV infusion.
DRUGOmeprazole
Administered orally as tablet or capsule in the acid-reducing agent assessment.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has Eastern Cooperative Oncology Group(ECOG) Performance Status of 0 or 1 * Has Life expectancy \>= 12 weeks * Adequate organ function * Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Inclusion Criteria for Dose-Finding Stage: * Histologically confirmed locally advanced or metastatic solid tumor that has progressed after at least one available standard therapy or for which approved standard therapy has proven to be ineffective or intolerable Inclusion Criteria for Expansion Stage: NSCLC Cohort * Histologically confirmed locally advanced or metastatic NSCLC * Absence of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) * PD- L1 positive * No prior systemic therapy for locally advanced or metastatic NSCLC Inclusion Criteria for Expansion Stage: HNSCC Cohort * Histologically confirmed recurrent, or metastatic HNSCC * PD-L1 positive * No prior systemic therapy for recurrent or metastatic HNSCC Inclusion Criteria for Expansion Stage: BRAF WT melanoma Cohort * Histologically confirmed locally advanced or metastatic or unresectable locally advanced cutaneous BRAF WT melanoma or melanomas of unknown primary that are non-mucosal and non -uveal that has progressed on or after treatment that included anti PD1 or anti PD-L1 therapy Inclusion Criteria for Expansion Stage: Other Advanced or Metastatic Solid Tumors Cohort * Histologically confirmed locally advanced or metastatic solid tumor that has progressed after at least one available standard therapy or for which approved standard therapy has proven to be ineffective or intolerable, standard therapy is considered inappropriate, or an investigational agent is a recognized standard of care
Exclusion criteria
* Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases. * Has leptomeningeal disease or carcinomatous meningitis * Has uncontrolled hypertension * Has left ventricular ejection fraction \< institutional lower limit of normal or \< 50% * Has clinically significant history of liver disease including viral or other hepatitis, current alcohol abuse, or cirrhosis * Has an active or history of autoimmune disease or immune deficiency including myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or multiple sclerosis. Participants with a history of autoimmune- related hypothyroidism on thyroid replacement hormone or with controlled Type I diabetes mellitus on a stable dose of an insulin regimen are eligible for this study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events (AEs) | Up to approximately 2.5 years |
| Percentage of Participants With Clinically Significant Change From Baseline in Vital Signs | Baseline up to 30 days after final dose of study treatment (up approximately to 2.5 years) |
| Percentage of Participants With Clinically Significant Change from Baseline in Clinical Laboratory Test Results | Baseline up to 30 days after final dose of study treatment (up approximately to 2.5 years) |
| Percentage of Participants With Clinically Significant Change From Baseline in RR and QT Intervals as Measured by Electrocardiogram (ECG) | Baseline up to 30 days after final dose of study treatment (up approximately to 2.5 years) |
| Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) | From Day 1 to Day 21 of Cycle 1 of the dose finding stage |
| Plasma Concentration of GDC-1971 | Up to approximately 2.5 years |
Secondary
| Measure | Time frame |
|---|---|
| PFS Rate | Month 6 |
| Cmax of GDC-1971 Following Tablet Administration Under Fasted and Fed Conditions | Up to approximately 2.5 years |
| AUC 0-24 hr at Steady State Following GDC-1971 Tablet Administration and in Combination With Omeprazole | Up to approximately 2.5 years |
| Area Under the Concentration-Time Curve From Time 0 to 96 hours (AUC0-96 hr) Following GDC-1971 Capsule or Tablet Administration | Up to approximately 2.5 years |
| Objective Response Rate (ORR) | Up to approximately 2.5 years |
| Duration of Response (DOR) | Up to approximately 2.5 years |
| Overall Survival (OS) Rate | Months 6 and 12 |
| Cmax at Steady State Following GDC-1971 Tablet Administration and in Combination With Omeprazole | Up to approximately 2.5 years |
| AUC From Time 0 to Infinity (AUCinf) Following GDC-1971 Capsule or Tablet Administration | Up to approximately 2.5 years |
| Cmax of GDC-1971 Following Capsule or Tablet Administration | Up to approximately 2.5 years |
| AUC 0-96 hr Following GDC-1971 Tablet Administration Under Fasted and Fed Conditions | Up to approximately 2.5 years |
| AUC inf Following GDC-1971 Tablet Administration Under Fasted and Fed Conditions | Up to approximately 2.5 years |
| Progression Free Survival (PFS) | Up to approximately 2.5 years |
Countries
Argentina, Australia, Brazil, Canada, New Zealand, South Korea
Outcome results
None listed