A Phase II, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of MOXR0916 in Combination With Atezolizumab Versus Atezolizumab Alone in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Therapy
Overview
- Phase
- Phase 2
- Intervention
- MOXR0916
- Conditions
- Urothelial Carcinoma
- Sponsor
- Genentech, Inc.
- Enrollment
- 5
- Locations
- 22
- Primary Endpoint
- Progression-Free Survival (PFS)
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
This is a Phase II, multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of MOXR0916 in combination with atezolizumab versus placebo and atezolizumab in participants with locally advanced or metastatic urothelial carcinoma (UC) who have not received prior systemic therapy in the locally advanced/metastatic setting and who are ineligible to receive cisplatin-based therapy.
Detailed Description
The study design has been amended after the decision to prematurely stop patient accrual due to enrollment challenges. As only 5 participants were enrolled, the study blinding will not be maintained, and placebo infusions will not be administered. Patients assigned to the MOXR0916 arm may continue study treatment with the combination of atezolizumab and MOXR0916 or with atezolizumab alone based on a discussion of benefit and risk with the treating investigator.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age \>= 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status of \<= 2
- •Life expectancy \>= 12 weeks
- •Histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma (UC)
- •Availability of a representative formalin-fixed paraffin-embedded tumor specimen
- •No prior systemic therapy for inoperable locally advanced or metastatic UC
- •Ineligible for cisplatin-based chemotherapy as defined by any one of the following criteria: Impaired renal function (glomerular filtration rate \[GFR\] \> 30 but \< 60 milliliter/minute \[mL/min\]); National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0 Grade \>= 2 audiometric hearing loss (of 25 Decibel at two contiguous frequencies or more severe); NCI CTCAE v 4.0 Grade \>= 2 peripheral neuropathy; ECOG Performance Status of 2
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1
- •Adequate hematologic and end-organ function
Exclusion Criteria
- •Significant cardiovascular disease
- •Known clinically significant liver disease
- •Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
- •Prior treatment with CD137 or OX40 agonists, anti-cytotoxic T-lymphocyte-associated protein (CTLA4), anti-programmed death-1 (PD-1), anti- programmed death-ligand 1 (PD-L1), anti-CD-27, anti- glucocorticoid-induced tumor necrosis factor receptor (GITR) therapeutic antibody or pathway-targeting agents
- •Untreated central nervous system (CNS) metastases or active (progressing or requiring corticosteroids for symptomatic control) CNS metastases
- •Any history of leptomeningeal disease
- •Malignancies other than UC within 5 years prior to Cycle 1, Day 1
- •History of autoimmune disease
- •History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan
- •Active hepatitis B and C virus infection
Arms & Interventions
MOXR0916 plus Atezolizumab
Intervention: MOXR0916
MOXR0916 plus Atezolizumab
Intervention: Atezolizumab
Atezolizumab
Intervention: Atezolizumab
Outcomes
Primary Outcomes
Progression-Free Survival (PFS)
Time Frame: Up to approximately 45 months
PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline); and an absolute increase of \>= 5 millimeter (mm) in the sum of diameters.
Overall Survival (OS)
Time Frame: Up to approximately 45 months
Kaplan Meier estimate of median OS was defined as the time at which half of the participants had died, regardless of the cause of death.
Secondary Outcomes
- Objective Response (OR) According to RECIST v1.1(Up to approximately 45 months)
- Duration of Objective Response (DOR) According to RECIST v1.1(Up to approximately 45 months)
- Time to Pain Progression, Pain Palliation, and Fatigue Progression as Measured by Participant-Reported Severity According to the M. D. Anderson Symptom Inventory (MDASI)(Up to approximately 45 months)
- Percentage of Participants Reporting Symptom Interference With Daily Living at the Time of Progression According to the MDASI(Up to approximately 45 months)
- Percentage of Participants With Adverse Event (AEs)(Up to approximately 45 months)
- Area Under the Plasma Drug Concentration-time Curve (AUC) of MOXR0916 and Atezolizumab(Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose)
- Maximum Plasma Concentration (Cmax) of MOXR0916 and Atezolizumab(Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose)
- Minimum Plasma Concentration (Cmin) of MOXR0916 and Atezolizumab(Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose)
- Clearance of MOXR0916 and Atezolizumab(Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose)
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to MOXR0916 and Atezolizumab(Cycles 1 - 4 and 8, 12, and 16 (each cycle is 21 days), Day 1: predose)