A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0919 Administered With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02471846
• Other study ID #: GO29779
• Secondary ID: 2015-001741-88
• Status: Completed
• Phase: Phase 1
• Start date: July 28, 2015
• Est. completion date: October 2, 2019

Study information

• Verified date: October 2019
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the safety, tolerability, and pharmacokinetics of the combination of GDC-0919 and atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy or for which standard therapy is ineffective, intolerable, or inappropriate. Participants will be enrolled in two stages, including a dose-escalation stage and an expansion stage.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 158
• Est. completion date: October 2, 2019
• Est. primary completion date: October 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Life expectancy at least 12 weeks

• Adequate hematologic and end organ function

• Negative pregnancy test and willingness to utilize contraception among women of childbearing potential

• Locally advanced, recurrent, or metastatic incurable solid malignancy with measurable disease per RECIST v1.1

• Progression following at least one standard therapy; or standard therapy considered ineffective, intolerable, or inappropriate; or use of an investigational agent recognized as a standard of care

• For the expansion stage, histologically confirmed renal cell cancer (RCC), urothelial bladder cancer (UBC), triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), melanoma, head and neck squamous cell carcinoma (HNSCC), gastric cancer, ovarian cancer, cervical cancer, endometrial cancer, or Merkel cell cancer

• For the expansion stage, evaluable for PD-L1 expression

• Anti PD-1/PD-L1 relapsed cohorts (I and II), participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade will be enrolled

Exclusion Criteria:

• Significant cardiovascular or liver disease

• Major surgery within 28 days of study drug

• Any anti-cancer therapy within 3 weeks of study drug

• Malabsorption syndrome or poor upper gastrointestinal integrity

• Primary central nervous system (CNS) malignancy or active metastases within 5 years

• Uncontrolled tumor pain

• Autoimmune disease other than stable hypothyroidism or vitiligo

• Human immunodeficiency virus (HIV), active hepatitis B or C, or tuberculosis

• Signs/symptoms of infection, or use of antibiotics within 2 weeks of study drug

• Live attenuated vaccine within 4 weeks of study drug

• Known history or predisposition to QT interval prolongation

• Prior cancer immunotherapy, specifically indoleamine 2,3-dioxygenase (IDO) or tryptophan 2,3-dioxygenase (TDO) inhibitors, T-cell costimulatory receptor agonist antibodies, or checkpoint inhibitors among certain participants

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• Atezolizumab
Participants will receive atezolizumab at a fixed dose of 1200 milligrams (mg) via intravenous (IV) infusion on Day 1 of each 21-day cycle with the exception of biopsy cohort A, where atezolizumab administration will start on Cycle 2 Day 1.
• GDC-0919
Participants will receive GDC-0919 by mouth (PO) twice daily (BID), specifically every 12 hours. During the dose-escalation stage, the first cohort will receive GDC-0919 at a starting dose of 50 mg PO BID. Dosing will commence on Day -1 for Cycle 1 and follow subsequent 21-day (Days 1 to 21) dosing cycles. The dose will be modified based upon evaluation of DLTs, with single dose escalations not to exceed 2.5-fold of the previous dose. The proposed dosages for evaluation are 50, 100, 200, 400, 600, and 1000 mg PO BID. During the expansion stage, selected solid tumor types will be treated at the MTD or MAD as determined during the dose-escalation stage.

Locations

Country	Name	City	State
France	Hopital Nord AP-HM	Marseille
France	Institut Gustave Roussy	Villejuif
Korea, Republic of	Asan Medical Center - Oncology	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario HM Sanchinarro-CIOCC	Madrid
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	University of Colorado	Aurora	Colorado
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	The Angeles Clinic and Research Institute, Santa Monica Office	Santa Monica	California
United States	HonorHealth Research Institute - Bisgrove	Scottsdale	Arizona
United States	H. Lee Moffitt Cancer Center and Research Inst.	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  France,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose-limiting Toxicities (DLTs)		From Day -1 to 21 of Cycle 1 (each cycle is 21 days)
Primary	Percentage of Participants With Adverse Events		From Screening until new anti-cancer therapy or up to 60 days after last dose (up to approximately 3 years)
Secondary	Maximum Tolerated Dose (MTD) of GDC-0919		From Day -1 to 21 of Cycle 1 (each cycle is 21 days)
Secondary	Recommended Phase II Dose (RP2D) for GDC-0919		From Day -1 to 21 of Cycle 1 (each cycle is 21 days)
Secondary	Number of Treatment Cycles Received With GDC-0919 and Atezolizumab		From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years)
Secondary	Dose Intensity of GDC-0919 and Atezolizumab		From Day -1 of Cycle 1 (each cycle is 21 days) until treatment discontinuation (up to approximately 3 years)
Secondary	Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab		Pre-dose from Day 1 of Cycle 1 (each cycle is 21 days) up to 120 days after last dose of atezolizumab (up to approximately 3 years)
Secondary	Plasma Maximum Concentration (Cmax) of GDC-0919		Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2
Secondary	Plasma Minimum Concentration (Cmin) of GDC-0919		Pre-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8
Secondary	Area Under the Concentration-time Curve to the Last Measurable Concentration (AUC0-last) of GDC-0919		Pre-dose and post-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8
Secondary	Time to Maximum Concentration (Tmax) of GDC-0919		Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2
Secondary	Serum Cmax of Atezolizumab		Post-dose from Day 1 of Cycle 1 (each cycle is 21 days) up to 120 days after last dose of atezolizumab (up to approximately 3 years)
Secondary	Serum Cmin of Atezolizumab		Pre-dose from Day 1 of Cycle 1 up to 120 days after last dose of atezolizumab (up to approximately 3 years)
Secondary	Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as Determined by the Investigator		From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years)
Secondary	Duration of Objective Response According to RECIST v1.1 as Determined by the Investigator		From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years)
Secondary	Percentage of Participants With Objective Response According to Modified RECIST as Determined by the Sponsor		From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years)
Secondary	Duration of Objective Response According to Modified RECIST as Determined by the Sponsor		From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years)