A Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) With Pembrolizumab in Participants With Selected Hyaluronan High Solid Tumors
NSCLC, Gastric Cancer
About this trial
This is an interventional treatment trial for NSCLC
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:
- 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.
- 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.
Sites / Locations
- University of Alabama at Birmingham
- Mayo Clinic, Scottsdale, Arizona
- California Cancer Associates for Research and Excellence - Encinitas
- University of California San Diego - Moores Cancer Center
- St. Joseph's Hospital
- University of California - Davis
- St. Joseph's Hospital
- Innovative Clinical Research
- University of Colorado Denver University of Colorado Anschutz Medical Campus
- Georgetown University Medical Center
- Holy Cross Hospitals
- University of Miami/Sylvester Cancer Center
- Cleveland Clinic Florida
- Emory University
- University of Chicago
- Ochsner Clinic Foundation
- Johns Hopkins Kimmel Cancer Center
- Barbara Ann Karmanos Cancer Center
- Washington University School of Medicine
- New Jersey Hematology Oncology Associates
- University of Rochester
- Gabrail Cancer Center
- Cleveland Clinic
- Ohio State University
- Oregon Health and Science University
- Mary Crowley Cancer Research Center
- Virginia Cancer Specialists, PC
- Swedish Health Services
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
GAC: PEGPH20 1.6 µg/kg/2.2 µg/kg + Pembrolizumab
NSCLC: PEGPH20 1.6 µg/kg/2.2 µg/kg + Pembrolizumab
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).
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).