A Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) With Pembrolizumab in Participants With Selected Hyaluronan High Solid Tumors

NCT ID: NCT02563548

Last Updated: 2020-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-22
• Study Completion Date: 2019-03-26

Brief Summary

This is a Phase 1b study evaluating a combination of PEGPH20 and pembrolizumab in hyaluronan-high (HA-high) participants with relapsed/refractory non-small cell lung cancer (NSCLC) and HA-high participants with relapsed/refractory gastric adenocarcinoma (GAC).

Detailed Description

Study involves dose escalation phase (completed in Nov-2016) to assess the safety and tolerability of PEGPEM (PEGylated recombinant human hyaluronidase [PEGPH20] combined with pembrolizumab [Keytruda®]) and to find the recommended Phase 2 dose (RP2D) ; and an expansion phase to assess the efficacy, safety and tolerability of PEGPEM in stage III b/IV NSCLC and relapsed/refractory GAC participants. Plan was to include approximately 51 HA-high participants (30 NSCLC and 21 GAC participants) in the dose expansion phase on the obtained RP2D from dose escalation phase of the study.

Conditions

NSCLC; Gastric Cancer

Study Design

• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GAC: PEGPH20 1.6 µg/kg/2.2 µg/kg + Pembrolizumab

Dose escalation part: Participants with relapsed/refractory locally advanced or metastatic gastric adenocarcinoma (GAC) will receive PEGPH20 1.6 micrograms/kilogram (µg/kg) or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 milligrams/kilogram (mg/kg) every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Dose expansion part: Participants with relapsed/refractory locally advanced or metastatic GAC will receive PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment in both phases of the study will continue until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks).

Group Type: EXPERIMENTAL

PEGPH20

Intervention Type: DRUG

PEGPH20 will be administered as an intravenous (IV) infusion as per the dose schedule specified in the arm description.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered as an IV infusion as per the dose schedule specified in the arm description.

NSCLC: PEGPH20 1.6 µg/kg/2.2 µg/kg + Pembrolizumab

Dose escalation part: Participants with relapsed/refractory Stage IIIB or IV non-small cell lung cancer (NSCLC) will receive PEGPH20 1.6 µg/kg or 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle (i.e. 3 doses/cycle) and pembrolizumab 2 mg/kg every 21 days on Day 1 of each cycle (i.e. 1 dose/cycle), 4-6 hours after the completion of PEGPH20 administration. Dose expansion part: Participants with relapsed/refractory Stage IIIB or IV NSCLC will receive PEGPH20 2.2 µg/kg on Day 1, Day 8 and Day 15 of each 21-day cycle and pembrolizumab 200 mg on Day 1 of each cycle, 4-6 hours after the completion of PEGPH20 administration. Treatment in both phases of the study will continue until death, withdrawal of consent from the study, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks).

Group Type: EXPERIMENTAL

PEGPH20

Intervention Type: DRUG

PEGPH20 will be administered as an intravenous (IV) infusion as per the dose schedule specified in the arm description.

Pembrolizumab

Intervention Type: DRUG

Pembrolizumab will be administered as an IV infusion as per the dose schedule specified in the arm description.

Interventions

PEGPH20

PEGPH20 will be administered as an intravenous (IV) infusion as per the dose schedule specified in the arm description.

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab will be administered as an IV infusion as per the dose schedule specified in the arm description.

Intervention Type: DRUG

Other Intervention Names

PEGylated recombinant human hyaluronidase; Keytruda®

Eligibility Criteria

Inclusion Criteria

• Dose Expansion: Histologically confirmed and documented, previously untreated or treated stage IIIB or IV NSCLC having failed no more than 1 previous platinum containing chemotherapy regimen for locally-advanced or metastatic disease or relapsed/refractory locally advanced or metastatic gastric adenocarcinoma having failed no more than 2 previous chemotherapy regimens for locally advanced or metastatic disease. Participants with NSCLC who are known to be epidermal growth factor receptor (EGFR)-mutation positive must have received an EGFR inhibitor and participants known to be anaplastic lymphoma kinase (ALK)-mutation positive must have received an ALK inhibitor.

Prior to enrollment, confirmation of the following must be obtained:

• For participants in the dose expansion portion of the study, it is mandatory that available archived tumor tissue in formalin-fixed.

paraffin-embedded (FFPE) block or minimum 10-15 unstained consecutive core biopsy slides from 1 archival block that meet specific tissue requirements are available.

• For dose expansion: one or more tumors measurable on computed tomography (CT) scan/magnetic resonance imaging (MRI) scan per RECIST v 1.1., for dose escalation, participants need only have evaluable disease - Previously irradiated tumors may be eligible if they have clearly progressed in size.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Life expectancy greater than or equal to (≥) 3 months.

Participants must also satisfy the following inclusion criterion to be enrolled in the dose expansion portion:

• Participants (NSCLC and gastric adenocarcinoma) must be determined to have HA-high levels from their tumor biopsies.
• NSCLC and gastric adenocarcinoma participants must have tissue available for HA-selection and programmed cell death-1 (PD-L1) testing.

Exclusion Criteria

• Previous treatment with pembrolizumab, nivolumab, or other antibody (anti-)-PD-1 or PD-1 ligand-antibody (anti-PD-L1) agents.
• New York Heart Association Class III or IV (Appendix D) cardiac disease or myocardial infarction within the past 12 months before screening, or preexisting atrial fibrillation.
• Prior history of cerebrovascular accident or transient ischemic attack.
• NSCLC participants with known brain metastases (certain exceptions allowed)
• Gastric adenocarcinoma participants with brain metastases
• History of active bleeding within the last 3 months requiring transfusion
• Anti-angiogenic therapy within the last month
• Participants with known interstitial fibrosis or interstitial lung disease.
• Previous history of pulmonary embolism or pulmonary embolism found on screening exam.
• History of:

1. Pneumonitis that requires oral or IV steroids;

2. Or known cases of hepatobiliary diseases (e.g., primary biliary cholangitis, primary sclerosing cholangitis, history of immune-mediated cholangitis);

• Participants with cholangitis attributed to infectious etiology (e.g., ascending cholangitis, bacterial cholangitis) are eligible if the infection has been fully resolved prior to the screening visit.

3. Or known cases of drug-induced hepatobiliary toxicities.

• Active autoimmune disease requiring systemic treatment within the past 3 months or documented history of clinically severe autoimmune disease, or syndrome that requires systemic steroids or immunosuppressive agents.
• History of another primary cancer within the last 3 years that required treatment, with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in situ.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Halozyme Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

VP, Clinical Development

Role: STUDY_DIRECTOR

Halozyme Therapeutics

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Mayo Clinic, Scottsdale, Arizona

Scottsdale, Arizona, United States

California Cancer Associates for Research and Excellence - Encinitas

Encinitas, California, United States

University of California San Diego - Moores Cancer Center

La Jolla, California, United States

St. Joseph's Hospital

Orange, California, United States

University of California - Davis

Sacramento, California, United States

St. Joseph's Hospital

Santa Rosa, California, United States

Innovative Clinical Research

Whittier, California, United States

University of Colorado Denver University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Holy Cross Hospitals

Fort Lauderdale, Florida, United States

University of Miami/Sylvester Cancer Center

Miami, Florida, United States

Cleveland Clinic Florida

Weston, Florida, United States

Emory University

Atlanta, Georgia, United States

University of Chicago

Chicago, Illinois, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, United States

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

New Jersey Hematology Oncology Associates

Brick, New Jersey, United States

University of Rochester

Rochester, New York, United States

Gabrail Cancer Center

Canton, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Oregon Health and Science University

Portland, Oregon, United States

Mary Crowley Cancer Research Center

Dallas, Texas, United States

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Swedish Health Services

Seattle, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

HALO-107-101

Identifier Type: -

Identifier Source: org_study_id