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

NCT02410512 | Completed Phase 1

• 2 other identifiers: GO296742015-000516-18
• Study Type: interventional
• Target: 610
• Locations: 7 countries
• Sites: 27

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.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (19)

• Maximum Tolerated Dose (MTD) of MOXR0916

  Up to 1 year

• Recommended Phase II Dose (RP2D) of MOXR0916

  Up to 1 year

• Percentage of Participants with Anti-MOXR0916 and Anti-Atezolizumab Antibodies

  Up to 120 days after the treatment discontinuation visit

• Number of Cycles Received with MOXR0916

  Baseline until treatment discontinuation (up to 3 years)

• Dose Intensity of MOXR0916

  Baseline until treatment discontinuation (up to 3 years)

Study Arms (2)

Dose Escalation: MOXR0916 + Atezolizumab

EXPERIMENTAL

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; Drug: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody

Expansion: MOXR0916 + Atezolizumab

EXPERIMENTAL

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; Drug: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody

Interventions

Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody DRUG

Atezolizumab will be administered intravenously.

Also known as: Tecentriq

Dose Escalation: MOXR0916 + Atezolizumab; Expansion: MOXR0916 + Atezolizumab

MOXR0916, a humanized agonist anti-OX40 monoclonal antibody DRUG

MOXR0916 will be administered intravenously.

Dose Escalation: MOXR0916 + Atezolizumab; Expansion: MOXR0916 + Atezolizumab

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (27)

HonorHealth Research Institute - Bisgrove

Scottsdale, Arizona, 85258, United States

Location

University of Colorado

Aurora, Colorado, 80045-2517, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Georgetown University Medical Center Lombardi Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

University Of Chicago Medical Center; Section Of Hematology/Oncology

Chicago, Illinois, 60637, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Can Ins

Boston, Massachusetts, 02215, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Chris O'Brien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Institut Jules Bordet

Anderlecht, 1070, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Sint Augustinus Wilrijk

Wilrijk, 2610, Belgium

Location

British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

University Health Network; Princess Margaret Hospital; Medical Oncology Dept

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

Montreal, Quebec, H3T 1E2, Canada

Location

Gustave Roussy

Villejuif, 94800, France

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Yonsei University Health System/Severance Hospital

Seoul, 120-752, South Korea

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal

Madrid, 28050, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

MeSH Terms

Conditions

Neoplasms

Interventions

atezolizumab; Antibodies

Intervention Hierarchy (Ancestors)

Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2015
• First Posted: April 7, 2015
• Study Start: April 24, 2015
• Primary Completion: November 22, 2019
• Study Completion: November 22, 2019
• Last Updated: April 1, 2022

Record last verified: 2022-03

Locations

US (9); CA (3); FR (1); AU (4); KR (3); ES (4); BE (3)