Clinical trial NCT02219724: A Study to Assess Safety and Pharmacokinetics of MOXR0916 in Participants With Locally Advanced or Metastatic Solid Tumors
Official title: A Phase I, Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of MOXR0916 Administered Intravenously as a Single Agent to Patients With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2014-08-19
Enrollment: 174
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Percentage of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 Up to Day 21 or 42
measure: 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)
timeFrame: 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 outcomes:
measure: Maximum Tolerated Dose (MTD) of MOXR0916
timeFrame: Baseline up to 21 to 42 days
measure: Recommended Phase II Dose of MOXR0916
timeFrame: Baseline up to 21 to 42 days
measure: Percentage of Participants With Anti-MOXR0916 Antibodies
timeFrame: 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
measure: Number of Cycles of MOXR0916 Treatment Received
timeFrame: Baseline up to approximately 3 years
measure: Mean MOXR0916 Dose Administered During Study
timeFrame: Baseline up to approximately 3 years
measure: Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC[0-last]) of MOXR0916
timeFrame: 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
measure: Maximum Observed Serum Concentration (Cmax) of MOXR0916
timeFrame: 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
measure: Minimum Observed Serum Concentration (Cmin) of MOXR0916
timeFrame: 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
measure: Serum Clearance (CL/F) of MOXR0916
timeFrame: 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
measure: Apparent Volume of Distribution at Steady State (Vss) of MOXR0916
timeFrame: 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
measure: Percentage of Participants With Objective Response as Determined Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: 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)
measure: Duration of Objective Response (DOR) as Determined Using RECIST v1.1
timeFrame: 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)
measure: Progression-free Survival (PFS) as Determined Using RECIST v1.1
timeFrame: 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)
measure: Percentage of Participants With Objective Response as Determined Using Modified RECIST
timeFrame: 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)
measure: DOR as Determined Using Modified RECIST
timeFrame: 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)
measure: PFS as Determined Using Modified RECIST
timeFrame: 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)
measure: Overall Survival (OS)
timeFrame: Baseline until death, loss to follow-up, withdrawal of consent, or study termination by the Sponsor (approximately up to 3 years)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute - Bisgrove
state: Arizona
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center Lombardi Cancer Center
state: District of Columbia
city: Chicago
country: United States
facility: University Of Chicago Medical Center; Section Of Hematology/Oncology
state: Illinois
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Can Ins
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Camperdown
country: Australia
facility: Chris O'Brien Lifehouse
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Gent
country: Belgium
facility: UZ Gent
city: Wilrijk
country: Belgium
facility: Sint Augustinus Wilrijk
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences - Juravinski Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre; Oncology
state: Ontario
city: Toronto
country: Canada
facility: University Health Network; Princess Margaret Hospital; Medical Oncology Dept
state: Ontario
city: Montreal
country: Canada
facility: McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
state: Quebec
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - Oncology
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System/Severance Hospital
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: