A Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) With Pembrolizumab in Participants With Selected Hyaluronan High Solid Tumors
Condition: NSCLC; Gastric Cancer
MeSH terms: Stomach Neoplasms
Intervention: PEGPH20; Pembrolizumab
Intervention description: PEGPH20 will be administered as an intravenous (IV) infusion as per the dose schedule specified in the arm description.; Pembrolizumab will be administered as an IV infusion as per the dose schedule specified in the arm description.
Intervention MeSH terms: Pembrolizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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).
    

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.