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

A Phase 1B Open-Label Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Pembrolizumab in Subjects With Selected Hyaluronan-High Solid Tumors

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).

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.

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.