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

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ClinicalTrials.gov Identifier: NCT02471846
Recruitment Status : Completed
First Posted : June 15, 2015
Last Update Posted : October 22, 2019
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE June 4, 2015
First Posted Date  ICMJE June 15, 2015
Last Update Posted Date October 22, 2019
Actual Study Start Date  ICMJE July 28, 2015
Actual Primary Completion Date October 2, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2016)
  • Percentage of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: From Day -1 to 21 of Cycle 1 (each cycle is 21 days) ]
  • Percentage of Participants With Adverse Events [ Time Frame: From Screening until new anti-cancer therapy or up to 60 days after last dose (up to approximately 3 years) ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 10, 2015)
  • Incidence and nature of dose-limiting toxicities (DLTs) [ Time Frame: From Day -1 to 21 of Cycle 1 ]
  • Incidence of adverse events [ Time Frame: From Screening until new anti-cancer therapy or up to 60 days after last dose (up to approximately 3 years) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 10, 2017)
  • Maximum Tolerated Dose (MTD) of GDC-0919 [ Time Frame: From Day -1 to 21 of Cycle 1 (each cycle is 21 days) ]
  • Recommended Phase II Dose (RP2D) for GDC-0919 [ Time Frame: From Day -1 to 21 of Cycle 1 (each cycle is 21 days) ]
  • Number of Treatment Cycles Received With GDC-0919 and Atezolizumab [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) ]
  • Plasma Maximum Concentration (Cmax) of GDC-0919 [ Time Frame: Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2 ]
  • Plasma Minimum Concentration (Cmin) of GDC-0919 [ Time Frame: Pre-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8 ]
  • Area Under the Concentration-time Curve to the Last Measurable Concentration (AUC0-last) of GDC-0919 [ Time Frame: Pre-dose and post-dose from Day -1 of Cycle 1 (each cycle is 21 days) through Day 1 of Cycle 8 ]
  • Time to Maximum Concentration (Tmax) of GDC-0919 [ Time Frame: Post-dose on Day -1 of Cycle 1 (each cycle is 21 days) and Day 1 of Cycle 2 ]
  • Serum Cmax of Atezolizumab [ Time Frame: 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) ]
  • Serum Cmin of Atezolizumab [ Time Frame: Pre-dose from Day 1 of Cycle 1 up to 120 days after last dose of atezolizumab (up to approximately 3 years) ]
  • 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 [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
  • Duration of Objective Response According to RECIST v1.1 as Determined by the Investigator [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
  • Percentage of Participants With Objective Response According to Modified RECIST as Determined by the Sponsor [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
  • Duration of Objective Response According to Modified RECIST as Determined by the Sponsor [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2015)
  • Number of treatment cycles received with GDC-0919 and MPDL3280A [ Time Frame: From Day -1 of Cycle 1 until treatment discontinuation (up to approximately 3 years) ]
  • Dose intensity with GDC-0919 and MPDL3280A [ Time Frame: From Day -1 of Cycle 1 until treatment discontinuation (up to approximately 3 years) ]
  • Incidence of anti-therapeutic antibody (ATA) response to MPDL3280A [ Time Frame: Pre-dose from Day 1 of Cycle 1 up to 120 days after last dose of MPDL3280A ]
  • Plasma Maximum Concentration (Cmax) of GDC-0919 [ Time Frame: Post-dose on Day -1 of Cycle 1 and Day 1 of Cycle 2 ]
  • Plasma Minimum Concentration (Cmin) of GDC-0919 [ Time Frame: Pre-dose from Day -1 of Cycle 1 up to Day 1 of Cycle 8 ]
  • Area Under the Concentration-time Curve to the Last Measurable Concentration (AUC0-last) of GDC-0919 [ Time Frame: Pre-dose and post-dose from Day -1 of Cycle 1 up to Day 1 of Cycle 8 ]
  • Time to Maximum Concentration (Tmax) of GDC-0919 [ Time Frame: Post-dose on Day -1 of Cycle 1 and Day 1 of Cycle 2 ]
  • Serum Cmax of MPDL3280A [ Time Frame: Post-dose from Day 1 of Cycle 1 up to 120 days after last dose of MPDL3280A ]
  • Serum Cmin of MPDL3280A [ Time Frame: Pre-dose from Day 1 of Cycle 1 up to 120 days after last dose of MPDL3280A ]
  • Objective response according to RECIST v1.1 [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
  • Duration of objective response according to RECIST v1.1 [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
  • Objective response according to modified RECIST [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
  • Duration of objective response according to modified RECIST [ Time Frame: From Screening until disease progression, death, new anti-cancer therapy, or premature study withdrawal (up to approximately 3 years) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of GDC-0919 and Atezolizumab Combination Treatment in Participants With Locally Advanced or Metastatic Solid Tumors
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE
  • 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.
    Other Names:
    • Tecentriq
    • MPDL3280A
    • RO5541267
  • Drug: 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.
Study Arms  ICMJE
  • Experimental: Anti-PD-1/PD-L1 Relapsed Cohort I
    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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: GDC-0919
  • Experimental: Anti-PD-1/PD-L1 Relapsed Cohort II
    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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: GDC-0919
  • Experimental: Biopsy Cohort A
    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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: GDC-0919
  • Experimental: Biopsy Cohort B
    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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: GDC-0919
  • Experimental: Dose-Escalation Cohort(s)
    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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: GDC-0919
  • Experimental: Expansion Cohorts
    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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: GDC-0919
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 3, 2017)
158
Original Estimated Enrollment  ICMJE
 (submitted: June 10, 2015)
224
Actual Study Completion Date  ICMJE October 2, 2019
Actual Primary Completion Date October 2, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Korea, Republic of,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02471846
Other Study ID Numbers  ICMJE GO29779
2015-001741-88 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Genentech, Inc.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP