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
- Conditions
- Neoplasms
- Interventions
- Drug: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody
- Registration Number
- NCT02410512
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 610
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation: MOXR0916 + Atezolizumab Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody 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). Expansion: MOXR0916 + Atezolizumab Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody 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. Expansion: MOXR0916 + Atezolizumab MOXR0916, a humanized agonist anti-OX40 monoclonal antibody 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. Dose Escalation: MOXR0916 + Atezolizumab MOXR0916, a humanized agonist anti-OX40 monoclonal antibody 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).
- Primary Outcome Measures
Name Time Method 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) 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
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Baseline until death (up to 3 years) Maximum Tolerated Dose (MTD) of MOXR0916 Up to 1 year Serum Maximum Observed Concentration (Cmax) of MOXR0916 Up to 120 days after the treatment discontinuation visit Serum Cmin of Atezolizumab Up to 120 days after the treatment discontinuation visit 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) Area under the Concentration-Time Curve (AUC) of MOXR0916 Up to 120 days after the treatment discontinuation visit Percentage of Participants with Objective Response Determined Using Modified RECIST Baseline until disease progression (up to 3 years) DOR Determined Using Modified RECIST From first objective response until death or relapse per RECIST v1.1, whichever occurs first (up to 3 years) Clearance (CL) of MOXR0916 Up to 120 days after the treatment discontinuation visit 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) PFS Determined Using Modified RECIST Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years) Number of Cycles Received with MOXR0916 Baseline until treatment discontinuation (up to 3 years) Serum Cmax of Atezolizumab Up to 120 days after the treatment discontinuation visit 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) 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 Dose Intensity of MOXR0916 Baseline until treatment discontinuation (up to 3 years) Serum Minimum Observed Concentration (Cmin) of MOXR0916 Up to 120 days after the treatment discontinuation visit Volume of Distribution at Steady State (Vss) of MOXR0916 Up to 120 days after the treatment discontinuation visit
Trial Locations
- Locations (27)
Gustave Roussy
🇫🇷Villejuif CEDEX, France
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
University of Colorado
🇺🇸Aurora, Colorado, United States
HonorHealth Research Institute - Bisgrove
🇺🇸Scottsdale, Arizona, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Georgetown University Medical Center Lombardi Cancer Center
🇺🇸Washington, District of Columbia, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
University Of Chicago Medical Center; Section Of Hematology/Oncology
🇺🇸Chicago, Illinois, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Dana Farber Can Ins
🇺🇸Boston, Massachusetts, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
UZ Gent
🇧🇪Gent, Belgium
Sint Augustinus Wilrijk
🇧🇪Wilrijk, Belgium
Institut Jules Bordet
🇧🇪Anderlecht, Belgium
British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
🇨🇦Toronto, Ontario, Canada
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
🇨🇦Montreal, Quebec, Canada
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal
🇪🇸Madrid, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Yonsei University Health System/Severance Hospital
🇰🇷Seoul, Korea, Republic of