Phase 1b Open-Label Study of 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 : June 5, 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) subjects with relapsed/refractory Non-Small Cell Lung Cancer (NSCLC) and HA-high subjects with relapsed/refractory gastric adenocarcinoma.

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

Detailed Description:

Study involves dose escalation phase (completed in Nov-2016) to find the RP2D dose and an expansion phase to assess the safety and tolerability of the RP2D dose within stage III b/IV NSCLC and relapsed/refractory gastric adenocarcinoma subjects.

Plan is to include approximately 51 HA-high subjects (30 NSCLC and 21 GAC subjects) in the dose expansion phase on the obtained RP2D from dose escalation phase of the study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 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
Study Start Date : October 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

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

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

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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 Non-Small Cell Lung Cancer (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. Subjects with NSCLC who are known to be epidermal growth factor receptor (EGFR)-mutation positive must have received an EGFR inhibitor and subjects 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:

• Dose expansion - For subjects in the dose expansion portion of the study, it is mandatory that available archived tumor tissue in FFPE block or minimum 10 unstained consecutive core biopsy slides from 1 archival block that meet specific tissue requirements are available.

  • One or more tumors measurable on CT scan/MRI scan per RECIST v 1.1. - 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 ≥3 months.

Subjects must also satisfy the following inclusion criterion:

  • Subjects (NSCLC and gastric adenocarcinoma) must be determined to have HA-high levels from their tumor biopsies.
  • NSCLC and gastric adenocarcinoma subjects must have tissue available for HA-selection and PD-L1 testing.

Exclusion Criteria:

  • Previous treatment with pembrolizumab, nivolumab, or other programmed cell death-1 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 subjects with known brain metastases (certain exceptions allowed)
  • Gastric adenocarcinoma subjects with brain metastases
  • History of active bleeding within the last 3 months requiring transfusion
  • Anti-angiogenic therapy within the last month
  • Patients 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);

      • Subjects 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

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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: June 5, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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