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

NCT02471846 | Completed Phase 1

• 2 other identifiers: GO297792015-001741-88
• Study Type: interventional
• Target: 158
• Locations: 4 countries
• Sites: 18

Brief 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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Dose-limiting Toxicities (DLTs)

  From Day -1 to 21 of Cycle 1 (each cycle is 21 days)

• 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 Outcomes (15)

• Maximum Tolerated Dose (MTD) of GDC-0919

  From Day -1 to 21 of Cycle 1 (each cycle is 21 days)

• Recommended Phase II Dose (RP2D) for GDC-0919

  From Day -1 to 21 of Cycle 1 (each cycle is 21 days)

• 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)

• 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)

• 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)

Study Arms (6)

Anti-PD-1/PD-L1 Relapsed Cohort I

EXPERIMENTAL

Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade and achieved best response of confirmed complete or partial response, or stable disease will receive GDC-0919, at the MTD or maximum administered dose (MAD) determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.

Drug: Atezolizumab; Drug: GDC-0919

Anti-PD-1/PD-L1 Relapsed Cohort II

EXPERIMENTAL

Approximately 20 participants whose most recent anti-cancer therapy consisted of single-agent PD-1/PD-L1 blockade and achieved unconfirmed partial response or stable disease will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.

Drug: Atezolizumab; Drug: GDC-0919

Biopsy Cohort A

EXPERIMENTAL

Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive GDC-0919 during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.

Drug: Atezolizumab; Drug: GDC-0919

Biopsy Cohort B

EXPERIMENTAL

Approximately 20 participants with melanoma, HNSCC, gastric, ovarian, Merkel cell, cervical, or endometrial cancer will receive atezolizumab during Cycle 1, followed by combination treatment with GDC-0919 and atezolizumab from Cycle 2 onwards. Serial biopsies of extrahepatic lesions will be performed. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.

Drug: Atezolizumab; Drug: GDC-0919

Dose-Escalation Cohort(s)

EXPERIMENTAL

Approximately 6 to 65 participants will be enrolled and treated at escalating doses of GDC-0919 in combination with fixed-dose atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio. Successive groups of at least 3 participants will be evaluated during a 21-day window for DLTs, which will determine the enrollment and dosing for subsequent cohorts in the dose-escalation stage. The MTD or MAD, whichever is reached first, will be considered for the expansion stage.

Drug: Atezolizumab; Drug: GDC-0919

Expansion Cohorts

EXPERIMENTAL

Approximately 160 participants (40 per diagnosis) with NSCLC, RCC, TNBC, and UBC will receive GDC-0919, at the MTD or MAD determined during the dose-escalation stage, in combination with Atezolizumab. Treatment may continue until unacceptable toxicity or disease progression with an unfavorable risk-benefit ratio.

Drug: Atezolizumab; Drug: GDC-0919

Interventions

Atezolizumab DRUG

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.

Also known as: Tecentriq, MPDL3280A, RO5541267

Anti-PD-1/PD-L1 Relapsed Cohort I; Anti-PD-1/PD-L1 Relapsed Cohort II; Biopsy Cohort A; Biopsy Cohort B; Dose-Escalation Cohort(s); Expansion Cohorts

GDC-0919 DRUG

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.

Anti-PD-1/PD-L1 Relapsed Cohort I; Anti-PD-1/PD-L1 Relapsed Cohort II; Biopsy Cohort A; Biopsy Cohort B; Dose-Escalation Cohort(s); Expansion Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (18)

HonorHealth Research Institute - Bisgrove

Scottsdale, Arizona, 85258, United States

Location

The Angeles Clinic and Research Institute, Santa Monica Office

Santa Monica, California, 90025, United States

Location

University of Colorado

Aurora, Colorado, 80045-2517, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

H. Lee Moffitt Cancer Center and Research Inst.

Tampa, Florida, 33612, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Hopital Nord AP-HM

Marseille, 13015, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center - Oncology

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 6351, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario HM Sanchinarro-CIOCC

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Related Publications (1)

• Jung KH, LoRusso P, Burris H, Gordon M, Bang YJ, Hellmann MD, Cervantes A, Ochoa de Olza M, Marabelle A, Hodi FS, Ahn MJ, Emens LA, Barlesi F, Hamid O, Calvo E, McDermott D, Soliman H, Rhee I, Lin R, Pourmohamad T, Suchomel J, Tsuhako A, Morrissey K, Mahrus S, Morley R, Pirzkall A, Davis SL. Phase I Study of the Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Navoximod (GDC-0919) Administered with PD-L1 Inhibitor (Atezolizumab) in Advanced Solid Tumors. Clin Cancer Res. 2019 Jun 1;25(11):3220-3228. doi: 10.1158/1078-0432.CCR-18-2740. Epub 2019 Feb 15.

  PMID: 30770348 DERIVED

MeSH Terms

Interventions

atezolizumab; navoximod

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: June 15, 2015
• Study Start: July 28, 2015
• Primary Completion: October 2, 2019
• Study Completion: October 2, 2019
• Last Updated: October 22, 2019

Record last verified: 2019-10

Locations

FR (2); US (10); ES (3); KR (3)