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
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody
- Conditions
- Neoplasms
- Sponsor
- Genentech, Inc.
- Enrollment
- 610
- Locations
- 27
- Primary Endpoint
- Number of Participants with Adverse Events Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.0
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
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).
Intervention: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody
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).
Intervention: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody
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.
Intervention: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody
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.
Intervention: MOXR0916, a humanized agonist anti-OX40 monoclonal antibody
Outcomes
Primary Outcomes
Number of Participants with Adverse Events Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.0
Time Frame: 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)
Time Frame: Days (D) 1-21 of Cycle (C) 1 (cycle = 21 days); up to D42 if extended monitoring warranted
Secondary Outcomes
- 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))
- Overall Survival (OS)(Baseline until death (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)