Advanced Non- small cell lung carcinoma (NSCLC)
Conditions
Interventions
Product Name: FRAME-001
Product Code: FRAME-001
Pharmaceutical Form: Solution for injection
Sponsors
Frame Pharmaceuticals B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age =18 years. - Eastern Cooperative Oncology Group (ECOG) performance status = 1 - -Pathologically and radiologically confirmed advanced squamous or non-squamous NSCLC with SD after four cycles of treatment with pembrolizumab as monotherapy or in combination with chemotherapy (carboplatin/cisplatin and pemetrexed/paclitaxel) and suitable for maintenance treatment with pembrolizumab monotherapy. - Patient Framome identification with demonstrated frameshift mutations (Frames) completed as part of molecular pre-screening: o Presence of at least 3 expressed frameshift mutations; o A combined length of ?100 amino acids for the neopeptides resulting from the frameshifts, with preferably more than 100 amino acids. o No mutations/genetic aberrations in genes relevant for MHC presentation (e.g., beta-2-microglobulin, human leukocyte antigen [HLA] genes). - An expected survival of at least 3 months. - Presence of tumor lesion(s) suitable for biopsy and radiological assessment as per RECIST v1.1 criteria. - Adequate renal function as defined by creatinine clearance > 40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR). - Adequate hepatic function as evidenced by: o Serum total bilirubin = 2.5 × upper limit of normal (ULN) unless considered due to hepatic metastases. o Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) = 3.0 × ULN, unless considered due to hepatic metastases. - Ability to return to the hospital for adequate follow-up as required by this protocol. - For all women of childbearing potential (defined as =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: - Any active infection that according to investigator might interfere with FRAME-001 vaccination. - Patients planned or foreseen to receive systemic immunosuppressive treatment including corticosteroids during the trial are not eligible. - Use of systemic corticosteroids (or other immunosuppressive agents; >10mg daily prednisone equivalent). Inhaled, intranasal or topical and physiological replacement doses of up to 10 mg daily prednisone equivalent are permitted. - Live vaccine within 30 days prior to first dose of FRAME-001. - Concomitant participation in another clinical intervention trial (except participation in a biobank study). - Pregnant or lactating women. - Known allergy to any of the ingredients of the vaccine (i.e., synthetic long peptides, Montanide ISA 51 VG). - Any medical or psychological condition deemed by the Investigator to be likely to interfere with a patient’s ability to give informed consent or participate in the study. - Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. - Patients with a currently active second malignancy. However, patients with the following history/concurrent conditions are allowed: o Basal or squamous cell carcinoma of the skin; o Carcinoma in situ of the cervix; o Carcinoma in situ of the breast; o Incidental histologic finding of prostate cancer.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine FRAME-001-specific immune responses in peripheral blood after administration of FRAME-001 to patients with advanced NSCLC. ;Secondary Objective: Secondary objectives - To assess safety and tolerability of FRAME-001. - To evaluate clinical anti-tumor response to FRAME-001. - To assess survival after treatment with FRAME-001. Exploratory objectives - To determine changes in the peripheral blood immune profile following FRAME-001 vaccination. - To assess molecular responses based on circulating tumor DNA (ctDNA) in plasma. - To assess immune responses in the tumor tissue before and after administration of FRAME-001. - Correlate FRAME-001-specific immune response to PD-L1 expression of the tumor and to Framome status. ;Primary end point(s): Antigen-specific immune responses in peripheral blood to one or more Frame peptides following application of a personalized FRAME-001 vaccine, based on a positive outcome in one or more of the following assays: - 4-Day interferon gamma (IFNg) enzyme-linked immunospot (ELISpot) assay; - IFNg, tumor necrosis factor alpha (TNFa), and/or interleukin-2 (IL-2) producing CD4+ and/or CD8+ T cells determined in intracellular cytokine staining assay; - Specific cytokine production as measured by Th1/Th2 cytokine bead array in culture supernatants. ;Timepoint(s) of evaluation of this end point: The primaire endpoint will be based on a positive outcome in one or more of the following assays: • 4-Day interferon gamma (IFNgamma) enzyme-linked immunospot (ELISpot) assay • IFNgamma, tumor necrosis factor alpha (TNFalpha), and/or interleukin-2 (IL-2) producing CD4+ and/or CD8+ T cells determined in intracellular cytokine staining assay • Specific cytokine production as measured by Th1/Th2 cytokine bead array in culture supernatants. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: These endpoints will be evaluated after termination of the trial after last patient last visit.;Secondary end point(s): Secondairy endpoints - Incidence, type, grade, and number of adverse events (AEs) according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. - Tumor response and tumor response duration according to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 criteria. - Progression-free survival (PFS) and overall survival (OS). Exploratory endpoints - Phenotypic composition of and functional changes in immune cells in peripheral blood and changes in plasma cytokine levels after vaccination with FRAME-001 determined by immunomonitoring assays, including but not limited to multiparametric flow cytometry, enzyme-linked immunoadsorbent assay (ELISA), functional T cell assays (T cell proliferation, cytokine production), T cell receptor repertoire, and other relevant immunological assays. - Relative change in immune cell infiltration and expression of PD-1 on tumor infiltrating lymphocytes and PD-L1 on tumor and immune cells in tumor biopsy (if available) after vaccination with FRAME-001. - Analysis of ctDNA in plasma. - Correlation of immune responses to PD-L1 expression of the tumor, and to Framome status. | — |
Countries
Netherlands
Contacts
Public ContactOperations Manager
Frame Pharmaceuticals B.V.
Outcome results
None listed