Clinical Trials /

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

NCT03417882

Description:

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

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: GRN-1201 With Pembrolizumab in Subjects With Metastatic PD-L1+ NSCLC
  • Official Title: A Pilot, Open-Label, Multi-Center, Multi-Dose Study of GRN-1201 Added to Pembrolizumab in Subjects With Non-Small Cell Lung Cancer With High PD-L1 Expression

Clinical Trial IDs

  • ORG STUDY ID: GRN-1201-002
  • NCT ID: NCT03417882

Conditions

  • Metastatic NSCLC

Interventions

DrugSynonymsArms
GRN-1201 + PembrolizumabPembrolizumabCohort 1

Purpose

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

Detailed Description

      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
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalAll 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.
  • GRN-1201 + Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Be male or female at least 18 years of age (at the time consent is obtained);

          2. Be able and willing to provide written informed consent and to comply with all
             requirements of study participation (including all study procedures);

          3. 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

          4. Have no prior systemic chemotherapy for metastatic disease: at least 6 months since
             prior adjuvant chemotherapy

          5. Be HLA-A*02+ as determined by Central Laboratory;

          6. Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue obtained from
             either a core or excisional tumor biopsy;

          7. Have a life expectancy of at least 3 months;

          8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;

          9. 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;

         10. 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

               -  Serum total bilirubin ≤ 1.5 x ULN OR

                  o Direct bilirubin ≤ ULN for subjects with total bilirubin >1.5 x ULN

               -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN
                  (≤ 5 x ULN for subjects with liver metastases)

               -  Albumin ≥2.5mg/dL

               -  International Normalized Ratio (INR) or PT/aPTT <1.5 x ULN. For subjects
                  receiving anticoagulation therapy, PT/aPTT and INR should not be greater than the
                  recommended range for the intended use of the anticoagulant

         11. Have recovered from the effects of any prior radiotherapy or surgery;

         12. Female subjects of childbearing potential must have a negative serum human chorionic
             gonadotropic (hCG) test within 1 week of Day 1 (pregnancy test not required for
             subjects with bilateral oophorectomy and/or hysterectomy or for those subjects who are
             >1 year post-menopausal); and

         13. All female and male subjects of reproductive potential must agree to use an effective
             method of contraception, as determined by the Investigator, during and for 4 months
             after the last dose of study treatment.

        Exclusion Criteria:

          1. 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;

          2. 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;

          3. 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;

          4. 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.

          5. 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;

          6. 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;

          7. Has carcinomatous meningitis;

          8. 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;

          9. Has history of interstitial lung disease, or history of (non-infectious) pneumonitis
             that required steroids, or current pneumonitis;

         10. 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;

         11. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected);

         12. History of myocardial infarction, unstable angina, cardiac or other vascular stenting,
             angioplasty, or surgery within 6 months prior to day 1 of study treatment;

         13. 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;

         14. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the study;

         15. 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;

         16. Is pregnant, breastfeeding, or expecting to conceive or father a child within the
             projected duration of the study including 120 days following the last dose of study
             treatment; or

         17. Has any concurrent medical condition that, in the opinion of the Investigator, would
             complicate or compromise compliance with the study or the well-being of the subject.

         18. Have an EGFR or ALK genomic tumor aberrations for which targeted therapy with an EGFR
             or ALK inhibitor is indicated.

             Additional Exclusion Criteria for Cohort 2:

         19. Has had prior treatment with an anti-PD-1 or anti-PD-L1 antibody, anti-cytotoxic
             T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab) or any
             other antibody or drug specifically targeting T-cell co-stimulation or checkpoint
             pathways;
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assess the effect, as measured by response rate of the addition of GRN-1201 to Pembrolizumab
Time Frame:First dose through 16 weeks after last dose of study drug
Safety Issue:
Description:Tumor assessment over time using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Secondary Outcome Measures

Measure:Evaluate the adverse event profile for the combination of GRN-1201 and Pembrolizumab as assessed by treatment -related events according to CTCAE version 4
Time Frame:First dose through 16 weeks after last dose of study drug
Safety Issue:
Description: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).
Measure:Host immune response to GRN-1201
Time Frame:First dose through 16 weeks after last dose of study drug
Safety Issue:
Description: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
Measure:Clinical Benefit response rate (CR + PR + SD >/= 16 weeks)
Time Frame:First dose through 16 weeks after last dose of study drug
Safety Issue:
Description:Tumor assessment over time using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Measure:Progression-free survival
Time Frame:First dose through 2 years after last dose of combination treatment
Safety Issue:
Description:Progression-free survival will be determined by tumor assessments or death from any cause
Measure:Duration of response in responding subjects
Time Frame:First dose through 16 weeks after last dose of study drug
Safety Issue:
Description:The duration of objective response will be assessed
Measure:Duration of clinical benefit
Time Frame:First dose through 16 weeks after last dose of study drug
Safety Issue:
Description:The duration of clinical benefit response rate will be assessed
Measure:Overall survival
Time Frame:First dose through 16 weeks after last dose of study drug
Safety Issue:
Description:All subjects will be followed for overall survival after discontinuation of combination treatment

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BrightPath Biotherapeutics

Trial Keywords

  • PD-L1+

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