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

Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02471846
Collaborator
(none)
158
Enrollment
18
Locations
6
Arms
50.2
Actual Duration (Months)
8.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
158 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jul 28, 2015
Actual Primary Completion Date :
Oct 2, 2019
Actual Study Completion Date :
Oct 2, 2019

Arms and Interventions

Arm Intervention/Treatment
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.

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.
    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.

    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.
    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.

    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.
    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.

    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.
    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.

    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.
    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.

    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.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Dose-limiting Toxicities (DLTs) [From Day -1 to 21 of Cycle 1 (each cycle is 21 days)]

    2. 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 Outcome Measures

    1. Maximum Tolerated Dose (MTD) of GDC-0919 [From Day -1 to 21 of Cycle 1 (each cycle is 21 days)]

    2. Recommended Phase II Dose (RP2D) for GDC-0919 [From Day -1 to 21 of Cycle 1 (each cycle is 21 days)]

    3. 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)]

    4. 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)]

    5. 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)]

    6. 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]

    7. 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]

    8. 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]

    9. 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]

    10. 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)]

    11. 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)]

    12. 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)]

    13. 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)]

    14. 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)]

    15. 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)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 HonorHealth Research Institute - Bisgrove Scottsdale Arizona United States 85258
    2 The Angeles Clinic and Research Institute, Santa Monica Office Santa Monica California United States 90025
    3 University of Colorado Aurora Colorado United States 80045-2517
    4 Yale Cancer Center New Haven Connecticut United States 06520
    5 H. Lee Moffitt Cancer Center and Research Inst. Tampa Florida United States 33612
    6 Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Baltimore Maryland United States 21231
    7 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    8 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    9 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    10 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    11 Hopital Nord AP-HM Marseille France 13015
    12 Institut Gustave Roussy Villejuif France 94805
    13 Seoul National University Hospital Seoul Korea, Republic of 03080
    14 Asan Medical Center - Oncology Seoul Korea, Republic of 05505
    15 Samsung Medical Center Seoul Korea, Republic of 6351
    16 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    17 Hospital Universitario HM Sanchinarro-CIOCC Madrid Spain 28050
    18 Hospital Clinico Universitario de Valencia Valencia Spain 46010

    Sponsors and Collaborators

    • Genentech, Inc.

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Genentech, Inc.
    ClinicalTrials.gov Identifier:
    NCT02471846
    Other Study ID Numbers:
    • GO29779
    • 2015-001741-88
    First Posted:
    Jun 15, 2015
    Last Update Posted:
    Oct 22, 2019
    Last Verified:
    Oct 1, 2019
    Additional relevant MeSH terms:
    Neoplasms
    Atezolizumab

    Study Results

    No Results Posted as of Oct 22, 2019