This is a non-randomized, Phase 2, 2-stage, open-label, multi-center study of GRN-1201/sargramostim + pembrolizumab in subjects with PD-L1+ metastatic NSCLC. All subjects will have newly diagnosed metastatic PD-L1+ (TPS ≥ 50%) NSCLC with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. Subjects with EGFR or ALK genomic tumor aberrations with progression on FDA-approved therapy for these aberrations are eligible
This is a non-randomized, Phase 2, 2-stage, open-label, multi-center study of GRN-1201/sargramostim + pembrolizumab in subjects with metastatic PD-L1+ NSCLC. All subjects will have newly diagnosed metastatic PD-L1+ (TPS ≥ 50%) NSCLC with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. The study will follow a Simon two-stage design with up to 64 total subjects enrolled. All subjects will receive GRN-1201 at 3.0 mg in combination with 75 µg sargramostim and 200 mg pembrolizumab. GRN-1201 is to be administered once weekly for 4 weeks followed by every 3-week dosing for an additional 12 doses (16 total doses of GRN-1201). Each dose of GRN-1201 will be given as 1 mL divided into 4 separate 0.25 mL intradermal injections on each day of treatment. Pembrolizumab is to be given every 3 weeks for up to a total of 35 doses. This study will consist of a screening period of up to 28 days; a treatment period consisting of GRN-1201/sargramostim administered weekly for 4 weeks (4 doses) followed by administration every 3 weeks for 12 additional doses . Pembrolizumab is to be given every 3 weeks for up to a total of 35 doses. A follow up visit will occur approximately 4 weeks after the last administration of treatment for the study. In addition, all subjects will be followed for evaluation of disease progression and survival
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
GRN-1201 will be administered in combination with Pembrolizumab
St Joseph Hospital of Orange
Orange, California, United States
University of Colorado Cancer Center
Aurora, Colorado, United States
Florida Hosptial Cancer Center- AdventHealth
Orlando, Florida, United States
Assess the effect, as measured by response rate of the addition of GRN-1201 to Pembrolizumab
Tumor assessment over time using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time frame: First dose through 16 weeks after last dose of study drug
Evaluate the adverse event profile for the combination of GRN-1201 and Pembrolizumab as assessed by treatment -related events according to CTCAE version 4
The safety and tolerability of GRN-1201/sargramostim + pembrolizumab will be evaluated by local and systemic signs and symptoms of injection site reactions, and incidence of adverse events including immune related adverse events (irAEs).
Time frame: First dose through 16 weeks after last dose of study drug
Host immune response to GRN-1201
Immune responses to GRN-1201 will be monitored to establish proof-of principle for the proposed pharmacological effect and demonstrate immunogenicity of GRN-1201. Immune response to the individual peptides will be assessed by measurement of cytotoxic T lymphocytes (CTLs) (by gamma interferon \[IFN-γ\] ELISPOT assay) and by measurement of antibodies to each peptide
Time frame: First dose through 16 weeks after last dose of study drug
Clinical Benefit response rate (CR + PR + SD >/= 16 weeks)
Tumor assessment over time using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time frame: First dose through 16 weeks after last dose of study drug
Progression-free survival
Progression-free survival will be determined by tumor assessments or death from any cause
Time frame: First dose through 2 years after last dose of combination treatment
Duration of response in responding subjects
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Robert H Lurie Cancer Center at Northwestern University
Chicago, Illinois, United States
University of Illinois at Chicago
Chicago, Illinois, United States
Orchard Healthcare
Skokie, Illinois, United States
Norton Healthcare Cancer Institute
Louisville, Kentucky, United States
East Jefferson General Hospital
Metairie, Louisiana, United States
Ocshner Cancer Institute
New Orleans, Louisiana, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States
...and 1 more locations
The duration of objective response will be assessed
Time frame: First dose through 16 weeks after last dose of study drug
Duration of clinical benefit
The duration of clinical benefit response rate will be assessed
Time frame: First dose through 16 weeks after last dose of study drug
Overall survival
All subjects will be followed for overall survival after discontinuation of combination treatment
Time frame: First dose through 16 weeks after last dose of study drug