Phase 1b Open-Label Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) With Pembrolizumab

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02563548
Recruitment Status : Active, not recruiting
First Posted : September 30, 2015
Last Update Posted : December 20, 2018
Information provided by (Responsible Party):
Halozyme Therapeutics

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).

Condition or disease Intervention/treatment Phase
NSCLC Gastric Cancer Drug: PEGPEM Drug: Pembrolizumab Phase 1

Detailed Description:
This study includes a dose-escalation phase (completed in Nov-2016) to assess the safety and tolerability of PEGPEM combined with pembrolizumab (Keytruda®) and find the recommended Phase 2 dose (RP2D). The study also includes a dose-expansion phase to assess the efficacy, safety, and tolerability of PEGPEM in stage III b/IV NSCLC and relapsed/refractory GAC participants. The study will include approximately 51 HA-high participants (30 NSCLC and 21 GAC participants) in the dose-expansion phase on the obtained RP2D from the dose-escalation phase of the study.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b Open-Label Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Pembrolizumab in Subjects With Selected Hyaluronan High Solid Tumors
Actual Study Start Date : October 31, 2015
Estimated Primary Completion Date : May 19, 2019
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: PEGPEM (PEGPH20 + pembrolizumab)

Dose-escalation phase: Participants will receive PEGPH20 administered intravenously (IV) on Day 1, Day 8, and Day 15 of each 21-day cycle (3 doses per cycle) and pembrolizumab administered IV (2 milligrams per kilogram [mg/kg] every 21 days) on Day 1 of each cycle (1 dose per cycle), 4 to 6 hours after the completion of PEGPH20 administration.

Dose-expansion phase: Participants will receive PEGPH20 administered IV at RP2D as determined in the dose-escalation phase on Day 1, Day 8, and Day 15 of each 21-day cycle and pembrolizumab 200 mg administered IV on Day 1 of each cycle, 4 to 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.

Other Name: Administered per the schedule specified in the arm description.

Drug: Pembrolizumab
Administered per schedule specified in the arm description.
Other Name: Keytruda®

Primary Outcome Measures :
  1. Efficacy of PEGPH20 and pembrolizumab combination by Objective response rate (ORR) [ Time Frame: Expansion phase ]
    based on RECIST v1.1 (Response Evaluation Criteria in Solid Tumors v.1.1) in Hyaluronan-high (HA-high) subjects

Secondary Outcome Measures :
  1. Duration of response (DOR) based on RECIST v1.1 and immune related response criteria (irRC) [ Time Frame: Expansion phase ]
    during the expansion phase

  2. Disease control rate (DCR) based on RECIST v1.1 and irRC [ Time Frame: Expansion phase ]
    during the expansion phase

  3. PFS based on RECIST v1.1 and irRC [ Time Frame: Expansion phase ]
    during expansion

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 regimen 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02563548

  Show 26 Study Locations
Sponsors and Collaborators
Halozyme Therapeutics

Responsible Party: Halozyme Therapeutics Identifier: NCT02563548     History of Changes
Other Study ID Numbers: HALO-107-101
First Posted: September 30, 2015    Key Record Dates
Last Update Posted: December 20, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Antineoplastic Agents