A Study to Assess Safety and Pharmacokinetics of MOXR0916 in Participants With Locally Advanced or Metastatic Solid Tumors
- Registration Number
- NCT02219724
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This is a first-in-human, Phase 1, open-label, multicenter, dose-escalation study designed to evaluate the safety, tolerability, and pharmacokinetics of MOXR0916 administered intravenously in participants with locally advanced or metastatic solid tumors that have progressed after all available standard therapy or for which standard therapy has proven to be ineffective or intolerable, or is considered inappropriate. This study will consist of a screening period, an initial treatment period, a re-treatment period (for participants who discontinue MOXR0916 after demonstration of prolonged clinical benefit), and a post-treatment follow-up period. Participants will be enrolled in two stages: a dose-escalation stage and an expansion stage. The planned duration of the study is approximately 3 years.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 174
- Histologic documentation of locally advanced, recurrent or metastatic incurable solid malignancy that has progressed after all available standard therapy or for which standard therapy has proven to be ineffective or intolerable, or is considered inappropriate
- Confirmed availability of representative tumor specimens in paraffin blocks/unstained slides
- Measurable disease per RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate hematologic and end organ function
- For female participants of childbearing potential, agreement to use highly effective form(s) of contraception and to continue its use for 6 months after the last dose of MOXR0916
- Any anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment (hormonal therapy with gonadotropin-releasing hormone agonists or antagonists for prostate cancer and palliative radiotherapy greater than (>) 2 weeks prior to Cycle 1, Day 1 are allowed)
- Eligibility based on prior treatment with immunomodulatory agents depends on the mechanistic class of the drug and the cohort for which the participant is being considered
- Adverse events from prior anti-cancer therapy that have not resolved to Grade less than or equal to (</=) 1 except for alopecia or endocrinopathy managed with replacement therapy
- Primary central nervous system (CNS) malignancy, or untreated/active CNS metastases
- Leptomeningeal disease
- Malignancies other than disease under study within 5 years
- History of autoimmune disease
- History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
- Positive test for human immunodeficiency virus infection
- Active hepatitis B or active hepatitis C
- Severe infections within 4 weeks or signs or symptoms of infection within 2 weeks prior to Cycle 1
- Prior allogeneic bone marrow transplantation or prior solid organ transplantation
- Significant cardiovascular disease
- Known clinically significant liver disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MOXR0916: Dose Escalation Stage MOXR0916 Participants in different cohorts (according to MOXR0916 dose received) will receive escalating doses of MOXR0916 to determine the MTD or maximum administered dose (MAD) for 21 to 42 days. MOXR0916: Expansion Stage MOXR0916 Participants in different cohorts (according to different cancer types, prior therapy and mandatory procedures on study) will receive MOXR0916 at the highest dose level that has already been deemed to be tolerable in the dose escalation stage until disease progression, loss of clinical benefit or unacceptable toxicity, whichever occurred first (approximately up to 3 years).
- Primary Outcome Measures
Name Time Method Percentage of Participants With Dose Limiting Toxicities (DLTs) Day 1 Up to Day 21 or 42 Percentage of Participants With Adverse Events (AEs) by Severity as Graded per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0) Baseline up to 90 days after the last dose of study treatment, or until the initiation of another systemic anti-cancer therapy, whichever occurs first (approximately up to 3 years)
- Secondary Outcome Measures
Name Time Method Mean MOXR0916 Dose Administered During Study Baseline up to approximately 3 years Number of Cycles of MOXR0916 Treatment Received Baseline up to approximately 3 years Maximum Tolerated Dose (MTD) of MOXR0916 Baseline up to 21 to 42 days Recommended Phase II Dose of MOXR0916 Baseline up to 21 to 42 days Percentage of Participants With Anti-MOXR0916 Antibodies Pre-dose (Hour [Hr] 0) on Day (D) 1 of Cycles (Cy) 1,2,3,4,8,12,16, & then every 8 Cy up to treatment discontinuation visit (TDV) (up to approximately 3 years) (1 Cy=21 days), thereafter every 30 days for up to 120 days after treatment discontinuation Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of MOXR0916 Cy1 (1Cy=21 days): Predose (Hr0), 0.5,24,72 hrs postinfusion (infusion duration=1.5 hrs) on D1; on D8, 15; Cy2-7: Hr0, 0.5 hrs postinfusion on D1; Cy8,12,16, then every 8 Cy up to TDV (approx. 3 years): Hr0 on D1; every 30 days after TDV up to 120 days DOR as Determined Using Modified RECIST Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years) Overall Survival (OS) Baseline until death, loss to follow-up, withdrawal of consent, or study termination by the Sponsor (approximately up to 3 years) Serum Clearance (CL/F) of MOXR0916 Cy1 (1Cy=21 days): Predose (Hr0), 0.5,24,72 hrs postinfusion (infusion duration=1.5 hrs) on D1; on D8, 15; Cy2-7: Hr0, 0.5 hrs postinfusion on D1; Cy8,12,16, then every 8 Cy up to TDV (approx. 3 years): Hr0 on D1; every 30 days after TDV up to 120 days Percentage of Participants With Objective Response as Determined Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years) Maximum Observed Serum Concentration (Cmax) of MOXR0916 Cy1 (1Cy=21 days): Predose (Hr0), 0.5,24,72 hrs postinfusion (infusion duration=1.5 hrs) on D1; on D8, 15; Cy2-7: Hr0, 0.5 hrs postinfusion on D1; Cy8,12,16, then every 8 Cy up to TDV (approx. 3 years): Hr0 on D1; every 30 days after TDV up to 120 days Minimum Observed Serum Concentration (Cmin) of MOXR0916 Cy1 (1Cy=21 days): Predose (Hr0), 0.5,24,72 hrs postinfusion (infusion duration=1.5 hrs) on D1; on D8, 15; Cy2-7: Hr0, 0.5 hrs postinfusion on D1; Cy8,12,16, then every 8 Cy up to TDV (approx. 3 years): Hr0 on D1; every 30 days after TDV up to 120 days Duration of Objective Response (DOR) as Determined Using RECIST v1.1 Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years) Apparent Volume of Distribution at Steady State (Vss) of MOXR0916 Cy1 (1Cy=21 days): Predose (Hr0), 0.5,24,72 hrs postinfusion (infusion duration=1.5 hrs) on D1; on D8, 15; Cy2-7: Hr0, 0.5 hrs postinfusion on D1; Cy8,12,16, then every 8 Cy up to TDV (approx. 3 years): Hr0 on D1; every 30 days after TDV up to 120 days Progression-free Survival (PFS) as Determined Using RECIST v1.1 Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years) Percentage of Participants With Objective Response as Determined Using Modified RECIST Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years) PFS as Determined Using Modified RECIST Baseline, end of Cycles 2, 4, 6, 8, and every 4 cycles thereafter (cycle length=21 days) until disease progression, death, another anti-cancer therapy initiation, loss to follow-up, consent withdrawal, or study termination (approximately up to 3 years)
Trial Locations
- Locations (31)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Chris O'Brien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
University Of Chicago Medical Center; Section Of Hematology/Oncology
🇺🇸Chicago, Illinois, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Dana Farber Can Ins
🇺🇸Boston, Massachusetts, United States
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Western Australia, Australia
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Georgetown University Medical Center Lombardi Cancer Center
🇺🇸Washington, District of Columbia, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
HonorHealth Research Institute - Bisgrove
🇺🇸Scottsdale, Arizona, United States
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
🇨🇦Montreal, Quebec, Canada
British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
Austin Hospital
🇦🇺Heidelberg, Victoria, Australia
Institut Jules Bordet
🇧🇪Brussels, Belgium
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal
🇪🇸Madrid, Spain
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Sint Augustinus Wilrijk
🇧🇪Wilrijk, Belgium
UZ Gent
🇧🇪Gent, Belgium
Hamilton Health Sciences - Juravinski Cancer Centre
🇨🇦Hamilton, Ontario, Canada
The Ottawa Hospital Cancer Centre; Oncology
🇨🇦Ottawa, Ontario, Canada
University Health Network; Princess Margaret Hospital; Medical Oncology Dept
🇨🇦Toronto, Ontario, Canada
Asan Medical Center - Oncology
🇰🇷Seoul, Korea, Republic of
Yonsei University Health System/Severance Hospital
🇰🇷Seoul, Korea, Republic of
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Clinica Universitaria de Navarra
🇪🇸Pamplona, Navarra, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain