Clincosm LogoSign in Get a demo

A Study to Assess the Safety and Pharmacokinetics of MOXR0916 and Atezolizumab (Also Known as MPDL3280A or Anti-PD-L1) in Participants With Locally Advanced or Metastatic Solid Tumors

Sponsor
Genentech, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02410512
Collaborator
(none)
610
Enrollment
27
Locations
2
Arms
55
Actual Duration (Months)
22.6
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase Ib, open-label, dose-escalation study will evaluate the safety, tolerability, and pharmacokinetics of the combination of MOXR0916 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 has proven to be ineffective or intolerable or is considered inappropriate; or for which a clinical trial of an investigational agent is a recognized standard of care. Participants will be enrolled in two stages: a dose-escalation stage and an expansion stage.

Condition or Disease Intervention/Treatment Phase
  • Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody
  • Drug: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody
 Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
610 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MOXR0916 and Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors
Actual Study Start Date :
Apr 24, 2015
Actual Primary Completion Date :
Nov 22, 2019
Actual Study Completion Date :
Nov 22, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose Escalation: MOXR0916 + Atezolizumab

Cohorts of at least 3 participants each will be treated at escalating doses of MOXR0916 in combination with a fixed dose of atezolizumab to determine the MTD or maximum administered dose (MAD).

Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody
Atezolizumab will be administered intravenously.
Other Names:
  • Tecentriq

    • Drug: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody
    MOXR0916 will be administered intravenously.
    Experimental: Expansion: MOXR0916 + Atezolizumab

    Approximately 250-580 participants will be enrolled in the expansion stage to better characterize the safety, tolerability, pharmacokinetic variability, biomarkers of anti-tumor activity, and preliminary efficacy of MOXR0916 + atezolizumab in different cancer types.

    Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody
    Atezolizumab will be administered intravenously.
    Other Names:
  • Tecentriq

    • Drug: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody
    MOXR0916 will be administered intravenously.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants with Dose-Limiting Toxicities (DLTs) [Days (D) 1-21 of Cycle (C) 1 (cycle = 21 days); up to D42 if extended monitoring warranted]

    2. Number of Participants with Adverse Events Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.0 [Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to 3 years)]

    Secondary Outcome Measures

    1. Maximum Tolerated Dose (MTD) of MOXR0916 [Up to 1 year]

    2. Recommended Phase II Dose (RP2D) of MOXR0916 [Up to 1 year]

    3. Percentage of Participants with Anti-MOXR0916 and Anti-Atezolizumab Antibodies [Up to 120 days after the treatment discontinuation visit]

    4. Number of Cycles Received with MOXR0916 [Baseline until treatment discontinuation (up to 3 years)]

    5. Dose Intensity of MOXR0916 [Baseline until treatment discontinuation (up to 3 years)]

    6. Area under the Concentration-Time Curve (AUC) of MOXR0916 [Up to 120 days after the treatment discontinuation visit]

    7. Serum Maximum Observed Concentration (Cmax) of MOXR0916 [Up to 120 days after the treatment discontinuation visit]

    8. Serum Minimum Observed Concentration (Cmin) of MOXR0916 [Up to 120 days after the treatment discontinuation visit]

    9. Clearance (CL) of MOXR0916 [Up to 120 days after the treatment discontinuation visit]

    10. Volume of Distribution at Steady State (Vss) of MOXR0916 [Up to 120 days after the treatment discontinuation visit]

    11. Serum Cmax of Atezolizumab [Up to 120 days after the treatment discontinuation visit]

    12. Serum Cmin of Atezolizumab [Up to 120 days after the treatment discontinuation visit]

    13. Percentage of Participants with Objective Response Determined Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Baseline until disease progression (up to 3 years)]

    14. Duration of Objective Response (DOR) Determined Using RECIST v1.1 [From first objective response until death or relapse per RECIST v1.1, whichever occurs first (up to 3 years)]

    15. Progression-Free Survival (PFS) Determined Using RECIST v1.1 [Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years)]

    16. Percentage of Participants with Objective Response Determined Using Modified RECIST [Baseline until disease progression (up to 3 years)]

    17. DOR Determined Using Modified RECIST [From first objective response until death or relapse per RECIST v1.1, whichever occurs first (up to 3 years)]

    18. PFS Determined Using Modified RECIST [Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years)]

    19. Overall Survival (OS) [Baseline until death (up to 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 0 or 1

    • Life expectancy of at least 12 weeks

    • Adequate hematologic and end organ function

    • Histologic documentation of locally advanced, recurrent, or metastatic incurable solid malignancy that has progressed after available standard therapy; or for which standard therapy is ineffective, intolerable, or considered inappropriate; or for which a clinical trial of an investigational agent is recognized standard of care

    • Tumor specimen availability

    • Measurable disease according to RECIST v1.1

    Exclusion Criteria:

    • Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment

    • Malignancies other than disease under study within 5 years prior to D1 of C1

    • Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases

    • History of leptomeningeal disease

    • History of idiopathic pulmonary fibrosis, pneumonitis (including drug-induced), organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted

    • History of autoimmune disease

    • Positive human immunodeficiency virus test result

    • Active hepatitis B, hepatitis C, or tuberculosis

    • Severe infection within 4 weeks prior to D1 of C1

    • Prior allogeneic bone marrow or solid organ transplantation

    • Significant cardiovascular disease

    • Known clinically significant liver disease

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 HonorHealth Research Institute - Bisgrove Scottsdale Arizona United States 85258
    2 University of Colorado Aurora Colorado United States 80045-2517
    3 Yale School of Medicine New Haven Connecticut United States 06510
    4 Georgetown University Medical Center Lombardi Cancer Center Washington District of Columbia United States 20007
    5 University Of Chicago Medical Center; Section Of Hematology/Oncology Chicago Illinois United States 60637
    6 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    7 Dana Farber Can Ins Boston Massachusetts United States 02215
    8 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    9 Seattle Cancer Care Alliance Seattle Washington United States 98109
    10 Chris O'Brien Lifehouse Camperdown New South Wales Australia 2050
    11 Austin Hospital Heidelberg Victoria Australia 3084
    12 Peter Maccallum Cancer Centre Melbourne Victoria Australia 3000
    13 Sir Charles Gairdner Hospital Nedlands Western Australia Australia 6009
    14 Institut Jules Bordet Anderlecht Belgium 1070
    15 UZ Gent Gent Belgium 9000
    16 Sint Augustinus Wilrijk Wilrijk Belgium 2610
    17 British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre Vancouver British Columbia Canada V5Z 4E6
    18 University Health Network; Princess Margaret Hospital; Medical Oncology Dept Toronto Ontario Canada M5G 2M9
    19 McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology Montreal Quebec Canada H3T 1E2
    20 Gustave Roussy Villejuif CEDEX France 94800
    21 Seoul National University Hospital Seoul Korea, Republic of 03080
    22 Asan Medical Center Seoul Korea, Republic of 05505
    23 Yonsei University Health System/Severance Hospital Seoul Korea, Republic of 120-752
    24 Clinica Universitaria de Navarra Pamplona Navarra Spain 31008
    25 Hospital Universitari Vall d'Hebron Barcelona Spain 08035
    26 Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal Madrid Spain 28050
    27 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:
    NCT02410512
    Other Study ID Numbers:
    • GO29674
    • 2015-000516-18
    First Posted:
    Apr 7, 2015
    Last Update Posted:
    Apr 1, 2022
    Last Verified:
    Mar 1, 2022
    Additional relevant MeSH terms:
    Atezolizumab
    Antibodies
    Immunoglobulins
    Antibodies, Monoclonal

    Study Results

    No Results Posted as of Apr 1, 2022