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A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-1971 in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors

Phase 1
Active, not recruiting
Conditions
Advanced Solid Tumors
Metastatic Solid Tumors
Interventions
Registration Number
NCT05487235
Lead Sponsor
Genentech, Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
232
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Expansion Stage: GDC-1971GDC-1971Participants will receive GDC-1971 orally at the assigned dose QD on Days 1-21 of each cycle and atezolizumab 1200 mg IV on Day 1 of each cycle until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet vs capsule formulation, the effect of food and acid-reducing agents on GDC-1971.
Dose-finding Stage: GDC-1971AtezolizumabParticipants will receive GDC-1971 tablet or capsule at assigned dose, orally once daily (QD) on Days 1-21 of each cycle, along with atezolizumab 1200 milligrams (mg) intravenous (IV) infusion once every 3 weeks (Q3W), until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet versus (vs) capsule formulations.
Dose-finding Stage: GDC-1971GDC-1971Participants will receive GDC-1971 tablet or capsule at assigned dose, orally once daily (QD) on Days 1-21 of each cycle, along with atezolizumab 1200 milligrams (mg) intravenous (IV) infusion once every 3 weeks (Q3W), until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet versus (vs) capsule formulations.
Expansion Stage: GDC-1971AtezolizumabParticipants will receive GDC-1971 orally at the assigned dose QD on Days 1-21 of each cycle and atezolizumab 1200 mg IV on Day 1 of each cycle until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet vs capsule formulation, the effect of food and acid-reducing agents on GDC-1971.
Expansion Stage: GDC-1971OmeprazoleParticipants will receive GDC-1971 orally at the assigned dose QD on Days 1-21 of each cycle and atezolizumab 1200 mg IV on Day 1 of each cycle until unacceptable toxicity or loss of clinical benefit. A subset of participants will participate in evaluations regarding tablet vs capsule formulation, the effect of food and acid-reducing agents on GDC-1971.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Clinically Significant Change From Baseline in Vital SignsBaseline up to 30 days after final dose of study treatment (up approximately to 2.5 years)
Percentage of Participants With Adverse Events (AEs)Up to approximately 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
Percentage of Participants With Clinically Significant Change from Baseline in Clinical Laboratory Test ResultsBaseline up to 30 days after final dose of study treatment (up approximately to 2.5 years)
Plasma Concentration of GDC-1971Up to approximately 2.5 years
Secondary Outcome Measures
NameTimeMethod
Area Under the Concentration-Time Curve From Time 0 to 96 hours (AUC0-96 hr) Following GDC-1971 Capsule or Tablet AdministrationUp to approximately 2.5 years
Cmax of GDC-1971 Following Capsule or Tablet AdministrationUp to approximately 2.5 years
AUC inf Following GDC-1971 Tablet Administration Under Fasted and Fed ConditionsUp to approximately 2.5 years
Objective Response Rate (ORR)Up to approximately 2.5 years
Progression Free Survival (PFS)Up to approximately 2.5 years
AUC From Time 0 to Infinity (AUCinf) Following GDC-1971 Capsule or Tablet AdministrationUp to approximately 2.5 years
Cmax of GDC-1971 Following Tablet Administration Under Fasted and Fed ConditionsUp to approximately 2.5 years
PFS RateMonth 6
Overall Survival (OS) RateMonths 6 and 12
AUC 0-96 hr Following GDC-1971 Tablet Administration Under Fasted and Fed ConditionsUp to approximately 2.5 years
AUC 0-24 hr at Steady State Following GDC-1971 Tablet Administration and in Combination With OmeprazoleUp to approximately 2.5 years
Cmax at Steady State Following GDC-1971 Tablet Administration and in Combination With OmeprazoleUp to approximately 2.5 years
Duration of Response (DOR)Up to approximately 2.5 years

Trial Locations

Locations (26)

Sanatorio Allende

🇦🇷

Cordoba, Argentina

Fundacion CORI para la Investigacion y Prevencion del Cancer

🇦🇷

La Rioja, Argentina

Centro Medico IPAM

🇦🇷

Rosario, Argentina

St Vincent's Hospital Sydney

🇦🇺

Darlinghurst, New South Wales, Australia

Border Medical Oncology

🇦🇺

Wodonga, New South Wales, Australia

Flinders Medical Centre

🇦🇺

Bedford Park, South Australia, Australia

Austin Hospital

🇦🇺

Heidelberg, Victoria, Australia

One Clinical Research Perth

🇦🇺

Nedlands, Western Australia, Australia

Liga Paranaense de Combate Ao Cancer - Hospital Erasto Gaertner

🇧🇷

Curitiba, Pará, Brazil

Hospital de Clinicas de Porto Alegre HCPA PPDS

🇧🇷

Porto Alegre, Pará, Brazil

Universidade de Caxias do Sul

🇧🇷

Caxias Do Sul, Rio Grande Do Sul, Brazil

Fundacao Pio XII Hospital de Cancer de Barretos

🇧🇷

Barretos, São Paulo, Brazil

Fundação Doutor Amaral Carvalho - Hospital Amaral

🇧🇷

JAU, São Paulo, Brazil

Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS

🇧🇷

Sao Jose Do Rio Preto, São Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP

🇧🇷

Sao Paulo, São Paulo, Brazil

Instituto Brasileiro de Controle Do Câncer IBCC

🇧🇷

São Paulo, Brazil

Cross Cancer Institute

🇨🇦

Edmonton, Alberta, Canada

Ottawa Hospital

🇨🇦

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

🇨🇦

Toronto, Ontario, Canada

Chungbuk National University Hospital

🇰🇷

Cheongju-si, Korea, Republic of

National Cancer Center

🇰🇷

Goyang-si, Korea, Republic of

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center - PPDS

🇰🇷

Seoul, Korea, Republic of

The Catholic University of Korea St. Vincent's Hospital

🇰🇷

Suwon-si, Korea, Republic of

Auckland City Hospital

🇳🇿

Auckland, New Zealand

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