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

NCT02563548 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HALO-107-101
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 28

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).

Conditions

NSCLC; Gastric Cancer

Outcome Measures

Primary Outcomes (4)

• Dose-Escalation Phase: Number of Participants With Dose-Limiting Toxicity (DLT)

  DLTs were defined as any of the following: i) Any treatment-emergent Grade greater than or equal to (≥) 3 toxicity that was considered related to either PEGPH20 or pembrolizumab or the combination of PEGPH20 and pembrolizumab (nausea, vomiting, MSEs, and diarrhea were considered DLTs only if they reached Grade ≥ 3 despite adequate supportive care measures); ii) Grade 3 musculoskeletal events (MSEs) were considered DLTs only if they did not reduce to Grade ≤ 2 within 48 hours despite therapeutic intervention; iii) Hypersensitivity/infusion reactions related to PEGPH20 or pembrolizumab dosing were not considered DLTs (hypersensitivity reactions were generally not related to the dose level of a drug since they could occur even upon a low level of exposure).

  Cycle 1 (21 days)

• Dose-Escalation Phase: Maximum Tolerated Dose (MTD) of PEGPH20 in Combination With Pembrolizumab

  MTD of PEGPEM combination (PEGPH20 + Pembrolizumab) was defined as the highest dose level at which no more than 1 of 6 evaluable participants had experienced a DLT in the first 3 weeks of treatment. DLT was defined as any of the following: i) Any treatment-emergent Grade greater than or equal to (≥) 3 toxicity that was considered related to either PEGPH20 or pembrolizumab or the combination of PEGPH20 and pembrolizumab (nausea, vomiting, MSEs, and diarrhea were considered DLTs only if they reached Grade ≥ 3 despite adequate supportive care measures); ii) Grade 3 musculoskeletal events (MSEs) were considered DLTs only if they did not reduce to Grade ≤ 2 within 48 hours despite therapeutic intervention; iii) Hypersensitivity/infusion reactions related to PEGPH20 or pembrolizumab dosing were not considered DLTs (hypersensitivity reactions were generally not related to the dose level of a drug since they could occur even upon a low level of exposure).

  Cycle 1 (21 days)

• Dose Escalation Phase: Recommended Phase 2 Dose (RP2D) of PEGPH20 in Combination With Pembrolizumab

  The RP2D was determined based on the overall safety profile of the participants enrolled during the dose-escalation part of the study.

  Cycle 1 (21 days)

• Dose Expansion Phase: Objective Response Rate (ORR): Percentage of Participants With Objective Response, as Assessed by Investigator Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  ORR was defined as percentage of participants who achieved either a complete response (CR) or partial response (PR), as assessed by investigator based on RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions; Any pathological or non-pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Cycle 1 Day 1 of dose-expansion phase until death, disease progression, or unacceptable toxicity (maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC)

Secondary Outcomes (17)

• Dose-Escalation Phase: ORR: Percentage of Participants With Objective Response, as Assessed by Investigator Based on RECIST Version 1.1

  Cycle 1 Day 1 of dose-escalation phase until death, disease progression, or unacceptable toxicity (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC)

• Dose-Escalation and Expansion Phase: Duration of Response (DOR), as Assessed by Investigator Based on RECIST v1.1

  From date of first objective response (CR or PR) until date of first radiographic disease progression (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC in dose-escalation; 60 weeks for GAC, and 46 weeks for NSCLC in dose-expansion)

• Dose-Escalation and Expansion Phase: Disease Control Rate (DCR), as Assessed by Investigator Based on RECIST v1.1: Percentage of Participants Who Achieved CR, PR or Stable Disease (SD)

  From first dose until first occurrence of CR, PR or SD (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC in dose-escalation phase; maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC in dose-expansion phase)

• Dose-Escalation and Expansion Phase: Progression-Free Survival (PFS), as Assessed by Investigator Based on RECIST v1.1

  From first dose until first occurrence of either radiographic or clinical disease progression or death (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC in dose-escalation; 60 weeks for GAC, and 46 weeks for NSCLC in dose-expansion)

• Dose-Escalation and Expansion Phase: Overall Survival

  From first dose until death from any cause (maximum exposure: 46 weeks for GAC, and 27 weeks for NSCLC in dose-escalation phase; maximum exposure: 60 weeks for GAC, and 46 weeks for NSCLC in dose-expansion phase)

Study Arms (2)

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

EXPERIMENTAL

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).

Drug: PEGPH20; Drug: Pembrolizumab

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

EXPERIMENTAL

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).

Drug: PEGPH20; Drug: Pembrolizumab

Interventions

PEGPH20 DRUG

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

Also known as: PEGylated recombinant human hyaluronidase

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

Pembrolizumab DRUG

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

Also known as: Keytruda®

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 (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.

You may not qualify if:

• 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:
• Pneumonitis that requires oral or IV steroids;
• 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.
• 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.

Sponsors & Collaborators

• Halozyme Therapeutics: lead

Study Sites (28)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Mayo Clinic, Scottsdale, Arizona

Scottsdale, Arizona, 85259-5499, United States

Location

California Cancer Associates for Research and Excellence - Encinitas

Encinitas, California, 92009, United States

Location

University of California San Diego - Moores Cancer Center

La Jolla, California, 92093, United States

Location

St. Joseph's Hospital

Orange, California, 92868, United States

Location

University of California - Davis

Sacramento, California, 95817, United States

Location

St. Joseph's Hospital

Santa Rosa, California, 95403, United States

Location

Innovative Clinical Research

Whittier, California, 90603, United States

Location

University of Colorado Denver University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Holy Cross Hospitals

Fort Lauderdale, Florida, 33308, United States

Location

University of Miami/Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

Cleveland Clinic Florida

Weston, Florida, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Johns Hopkins Kimmel Cancer Center

Baltimore, Maryland, 21231, United States

Location

Barbara Ann Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63130, United States

Location

New Jersey Hematology Oncology Associates

Brick, New Jersey, 08724, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75251, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Swedish Health Services

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

PEGPH20; pembrolizumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Limitations and Caveats

Due to evolving standard-of-care in the immuno-oncology treatment landscape, this study discontinued further enrollment on 31 May 2018.

Results Point of Contact

• Title: VP, Clinical Development
• Organization: Halozyme Therapeutics

medinfo@halozyme.com

858-794-8889

Study Officials

• VP, Clinical Development

  Halozyme Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2015
• First Posted: September 30, 2015
• Study Start: October 22, 2015
• Primary Completion: March 26, 2019
• Study Completion: March 26, 2019
• Last Updated: February 7, 2020
• Results First Posted: February 7, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (28)