Neoplasms
Conditions
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.
Interventions
DRUGAtezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody
Atezolizumab will be administered intravenously.
DRUGMOXR0916, a humanized agonist anti-OX40 monoclonal antibody
MOXR0916 will be administered intravenously.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) |
| Area under the Concentration-Time Curve (AUC) of MOXR0916 | Up to 120 days after the treatment discontinuation visit |
| Serum Maximum Observed Concentration (Cmax) of MOXR0916 | Up to 120 days after the treatment discontinuation visit |
| Serum Minimum Observed Concentration (Cmin) of MOXR0916 | Up to 120 days after the treatment discontinuation visit |
| 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) |
| Serum Cmax of Atezolizumab | 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) |
| 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) |
| 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) |
| PFS Determined Using Modified RECIST | Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years) |
| Overall Survival (OS) | Baseline until death (up to 3 years) |
| Volume of Distribution at Steady State (Vss) of MOXR0916 | Up to 120 days after the treatment discontinuation visit |
| Maximum Tolerated Dose (MTD) of MOXR0916 | Up to 1 year |
Countries
Australia, Belgium, Canada, France, South Korea, Spain, United States
Outcome results
None listed