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

Genentech, Inc.31 sites in 6 countries174 target enrollmentAugust 12, 2014

ConditionsNeoplasms

InterventionsMOXR0916

DrugsMOXR0916

Overview

Phase: Phase 1
Intervention: MOXR0916
Conditions: Neoplasms
Sponsor: Genentech, Inc.
Enrollment: 174
Locations: 31
Primary Endpoint: Percentage of Participants With Dose Limiting Toxicities (DLTs)
Status: Completed
Last Updated: 6 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

August 12, 2014

End Date

August 18, 2019

Last Updated

6 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Genentech, Inc.

Responsible Party

Sponsor

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

Arms & Interventions

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.

Intervention: MOXR0916

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).

Intervention: MOXR0916

Outcomes

Primary Outcomes

Percentage of Participants With Dose Limiting Toxicities (DLTs)

Time Frame: 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)

Time Frame: 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

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)
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))