GRN-1201 With Pembrolizumab in Subjects With Metastatic PD-L1+ NSCLC

NCT03417882 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: GRN-1201-002
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 11

Brief Summary

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

Conditions

Metastatic NSCLC

Keywords

PD-L1+

Outcome Measures

Primary Outcomes (1)

• 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

  First dose through 16 weeks after last dose of study drug

Secondary Outcomes (7)

• Evaluate the adverse event profile for the combination of GRN-1201 and Pembrolizumab as assessed by treatment -related events according to CTCAE version 4

  First dose through 16 weeks after last dose of study drug

• Host immune response to GRN-1201

  First dose through 16 weeks after last dose of study drug

• Clinical Benefit response rate (CR + PR + SD >/= 16 weeks)

  First dose through 16 weeks after last dose of study drug

• Progression-free survival

  First dose through 2 years after last dose of combination treatment

• Duration of response in responding subjects

  First dose through 16 weeks after last dose of study drug

Study Arms (1)

Cohort 1

EXPERIMENTAL

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.

Biological: GRN-1201 + Pembrolizumab

Interventions

GRN-1201 + Pembrolizumab BIOLOGICAL

GRN-1201 will be administered in combination with Pembrolizumab

Also known as: Pembrolizumab

Cohort 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be male or female at least 18 years of age (at the time consent is obtained);
• Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures);
• Have histologically- or cytologically-confirmed diagnosis of Stage IV NSCLC Have newly diagnosed, metastatic NSCLC with PD-L1 TPS ≥ 50% (as determined by central lab using the 22C3 pharmDx kit) Note: Subjects with documentation of PD-L1 TPS ≥50% by IHC analysis using the 22C3 pharmDx kit will not require repeat PD-L1 testing by central laboratory and
• Have no prior systemic chemotherapy for metastatic disease: at least 6 months since prior adjuvant chemotherapy
• Be HLA-A\*02+ as determined by Central Laboratory;
• Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue obtained from either a core or excisional tumor biopsy;
• Have a life expectancy of at least 3 months;
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the site study team. Target tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions;
• Has adequate organ function as defined by:
• Absolute neutrophil count ≥ 1,500/µL
• Platelets ≥ 100,000/µL
• Hemoglobin ≥ 9 g/dL (without transfusion for at least one month)
• Serum creatinine ≤ 1.5 x Upper Limit of Normal (ULN) OR
• o glomerular filtration rate (GFR) ≥30mL/min if serum creatinine \> 1.5 x ULN, creatinine clearance may be calculated using the institutional/laboratory standard method

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 14 days of the first dose of treatment;
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy \> 10 mg prednisone or equivalent per day or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment;
• Has undergone major surgery within 3 weeks of Study Day 1, Subject must have recovered adequately from any toxicity and/or complications from the intervention prior to starting therapy;
• Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including granulocyte colony-stimulating factor \[G-CSF\], GM-CSF or recombinant erythropoietin) within 4 weeks prior to study Day 1;
• Has known active central nervous system (CNS) metastases NOTE: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging \[using the identical imaging modality for each assessment, either magnetic resonance imaging (MRI) or computerized tomography (CT) scan\] for at least four weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study treatment;
• Has carcinomatous meningitis;
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment NOTE: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study;
• Has history of interstitial lung disease, or history of (non-infectious) pneumonitis that required steroids, or current pneumonitis;
• Has an active infection requiring systemic therapy NOTE: Antibiotic therapy must have been completed a minimum of 3 days prior to start of study treatment;
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected);
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to day 1 of study treatment;
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator;
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study;
• Has received a live virus vaccine within 30 days of the planned first dose of study therapy NOTE: seasonal influenza vaccines for injection which are generally inactivated flu vaccines are permitted; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines and are not permitted;

Sponsors & Collaborators

• BrightPath Biotherapeutics: lead

Study Sites (11)

St Joseph Hospital of Orange

Orange, California, 92868, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Florida Hosptial Cancer Center- AdventHealth

Orlando, Florida, 32804, United States

Location

Robert H Lurie Cancer Center at Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Orchard Healthcare

Skokie, Illinois, 60077, United States

Location

Norton Healthcare Cancer Institute

Louisville, Kentucky, 40202, United States

Location

East Jefferson General Hospital

Metairie, Louisiana, 70006, United States

Location

Ocshner Cancer Institute

New Orleans, Louisiana, 70121, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23230, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study will follow a Simon two-stage design \[1\] with up to 64 subjects enrolled. All subjects will receive GRN-1201 at a dose of 3.0 mg per peptide in combination with 75 µg sargramostim (Leukine®) and 200 mg pembrolizumab.

Study Record Dates

• First Submitted: November 14, 2017
• First Posted: January 31, 2018
• Study Start: January 3, 2019
• Primary Completion: December 5, 2022
• Study Completion: December 5, 2022
• Last Updated: August 8, 2023

Record last verified: 2023-08

Locations

US (11)