A Study to Assess Safety and Pharmacokinetics of MOXR0916 in Participants With Locally Advanced or Metastatic Solid Tumors

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02219724
• Other study ID #: GO29313
• Secondary ID: 2014-001474-34
• Status: Completed
• Phase: Phase 1
• Start date: August 12, 2014
• Est. completion date: August 18, 2019

Study information

• Verified date: February 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 174
• Est. completion date: August 18, 2019
• Est. primary completion date: July 14, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• MOXR0916
MOXR0916 will be administered as intravenous infusion on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
Australia	Chris O'Brien Lifehouse	Camperdown	New South Wales
Australia	Austin Hospital	Heidelberg	Victoria
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Belgium	Institut Jules Bordet	Brussels
Belgium	UZ Gent	Gent
Belgium	Sint Augustinus Wilrijk	Wilrijk
Canada	Hamilton Health Sciences - Juravinski Cancer Centre	Hamilton	Ontario
Canada	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec
Canada	The Ottawa Hospital Cancer Centre; Oncology	Ottawa	Ontario
Canada	University Health Network; Princess Margaret Hospital; Medical Oncology Dept	Toronto	Ontario
Canada	British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre	Vancouver	British Columbia
Korea, Republic of	Asan Medical Center - Oncology	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Yonsei University Health System/Severance Hospital	Seoul
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal	Madrid
Spain	Clinica Universitaria de Navarra	Pamplona	Navarra
Spain	Hospital Clinico Universitario de Valencia	Valencia
United States	University of Colorado	Aurora	Colorado
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Can Ins	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University Of Chicago Medical Center; Section Of Hematology/Oncology	Chicago	Illinois
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale School of Medicine	New Haven	Connecticut
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	HonorHealth Research Institute - Bisgrove	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Georgetown University Medical Center Lombardi Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Dose Limiting Toxicities (DLTs)		Day 1 Up to Day 21 or 42
Primary	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	Maximum Tolerated Dose (MTD) of MOXR0916		Baseline up to 21 to 42 days
Secondary	Recommended Phase II Dose of MOXR0916		Baseline up to 21 to 42 days
Secondary	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
Secondary	Number of Cycles of MOXR0916 Treatment Received		Baseline up to approximately 3 years
Secondary	Mean MOXR0916 Dose Administered During Study		Baseline up to approximately 3 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Overall Survival (OS)		Baseline until death, loss to follow-up, withdrawal of consent, or study termination by the Sponsor (approximately up to 3 years)