A Study to Assess the Safety and Pharmacokinetics of MOXR0916 and Atezolizumab (Also Known as MPDL3280A or Anti-PD-L1) in Participants With Locally Advanced or Metastatic Solid Tumors

Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02410512
• Other study ID #: GO29674
• Secondary ID: 2015-000516-18
• Status: Completed
• Phase: Phase 1
• Start date: April 24, 2015
• Est. completion date: November 22, 2019

Study information

• Verified date: March 2022
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 610
• Est. completion date: November 22, 2019
• Est. primary completion date: November 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• Significant cardiovascular disease

• Known clinically significant liver disease

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 [PD-L1] antibody
Atezolizumab will be administered intravenously.
• MOXR0916, a humanized agonist anti-OX40 monoclonal antibody
MOXR0916 will be administered intravenously.

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	Anderlecht
Belgium	UZ Gent	Gent
Belgium	Sint Augustinus Wilrijk	Wilrijk
Canada	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec
Canada	University Health Network; Princess Margaret Hospital; Medical Oncology Dept	Toronto	Ontario
Canada	British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre	Vancouver	British Columbia
France	Gustave Roussy	Villejuif CEDEX
Korea, Republic of	Asan Medical Center	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	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Can Ins	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	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,  France,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Dose-Limiting Toxicities (DLTs)		Days (D) 1-21 of Cycle (C) 1 (cycle = 21 days); up to D42 if extended monitoring warranted
Primary	Number of Participants with Adverse Events Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 4.0		Baseline until 90 days after last dose or initiation of another systemic anti-cancer therapy, whichever occurs first (up to 3 years)
Secondary	Maximum Tolerated Dose (MTD) of MOXR0916		Up to 1 year
Secondary	Recommended Phase II Dose (RP2D) of MOXR0916		Up to 1 year
Secondary	Percentage of Participants with Anti-MOXR0916 and Anti-Atezolizumab Antibodies		Up to 120 days after the treatment discontinuation visit
Secondary	Number of Cycles Received with MOXR0916		Baseline until treatment discontinuation (up to 3 years)
Secondary	Dose Intensity of MOXR0916		Baseline until treatment discontinuation (up to 3 years)
Secondary	Area under the Concentration-Time Curve (AUC) of MOXR0916		Up to 120 days after the treatment discontinuation visit
Secondary	Serum Maximum Observed Concentration (Cmax) of MOXR0916		Up to 120 days after the treatment discontinuation visit
Secondary	Serum Minimum Observed Concentration (Cmin) of MOXR0916		Up to 120 days after the treatment discontinuation visit
Secondary	Clearance (CL) of MOXR0916		Up to 120 days after the treatment discontinuation visit
Secondary	Volume of Distribution at Steady State (Vss) of MOXR0916		Up to 120 days after the treatment discontinuation visit
Secondary	Serum Cmax of Atezolizumab		Up to 120 days after the treatment discontinuation visit
Secondary	Serum Cmin of Atezolizumab		Up to 120 days after the treatment discontinuation visit
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Percentage of Participants with Objective Response Determined Using Modified RECIST		Baseline until disease progression (up to 3 years)
Secondary	DOR Determined Using Modified RECIST		From first objective response until death or relapse per RECIST v1.1, whichever occurs first (up to 3 years)
Secondary	PFS Determined Using Modified RECIST		Baseline until death or disease progression per RECIST v1.1, whichever occurs first (up to 3 years)
Secondary	Overall Survival (OS)		Baseline until death (up to 3 years)