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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: MOXR0916

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Belgium
  • Brussels, Belgium, 1000
    • Institut Jules Bordet
  • Gent, Belgium, 9000
    • UZ Gent
  • Wilrijk, Belgium, 2610
    • Sint Augustinus Wilrijk
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency (Bcca) - Vancouver Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Hamilton Health Sciences - Juravinski Cancer Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre; Oncology
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network; Princess Margaret Hospital; Medical Oncology Dept
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center - Oncology
  • Seoul, Korea, Republic of, 120-752
    • Yonsei University Health System/Severance Hospital
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28050
    • Hosp de Madrid Norte Sanchinarro; Centro Integral; Onco Clara Campal
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria De Navarra
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute - Bisgrove
  • Colorado
    • Aurora, Colorado, United States, 80045-2517
      • University of Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center Lombardi Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University Of Chicago Medical Center; Section Of Hematology/Oncology
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Can Ins
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MOXR0916: Dose Escalation Stage; 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.	Drug: MOXR0916; MOXR0916 will be administered as intravenous infusion on Day 1 of each 21-day cycle.
Experimental: MOXR0916: Expansion Stage; 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).	Drug: MOXR0916; MOXR0916 will be administered as intravenous infusion on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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
Number of Cycles of MOXR0916 Treatment Received	Baseline up to approximately 3 years
Mean MOXR0916 Dose Administered During Study	Baseline up to approximately 3 years
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
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
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
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
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)
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)
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)
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)
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)
Overall Survival (OS)	Baseline until death, loss to follow-up, withdrawal of consent, or study termination by the Sponsor (approximately up to 3 years)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2014
• Primary Completion (Actual): July 14, 2017
• Study Completion (Actual): August 18, 2019

Study Registration Dates

• First Submitted: August 15, 2014
• First Submitted That Met QC Criteria: August 15, 2014
• First Posted (Estimate): August 19, 2014

Study Record Updates

• Last Update Posted (Actual): February 5, 2020
• Last Update Submitted That Met QC Criteria: February 3, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: GO29313; 2014-001474-34 (EudraCT Number)