OncoMatch/Clinical Trials/NCT05254184
KRAS-Targeted Vaccine With Chemoimmunotherapy, Nivolumab and Ipilimumab for Patients With NSCLC
Is NCT05254184 recruiting? Yes, currently enrolling (May 2026). This Phase 1 trial studies Pooled Mutant KRAS-Targeted Long Peptide Vaccine 0.3mg each; 1.8mg total peptides for non-small cell lung cancer.
Treatment: Pooled Mutant KRAS-Targeted Long Peptide Vaccine 0.3mg each; 1.8mg total peptides — This is a single institution, Phase 1 study for patients with Stage III/IV unresectable Kirsten rat sarcoma (KRAS) mutated NSCLC to evaluate safety of the pooled mutant-KRAS peptide vaccine (KRAS peptide vaccine) with polyinosinic-polycytidylic acid (poly-ICLC) adjuvant in combination with chemoimmunotherapy, nivolumab and ipilimumab in the first line treatment setting. The primary objectives of this study are to determine the safety and feasibility of administering the KRAS peptide vaccine with poly-ICLC adjuvant with chemoimmunotherapy nivolumab and ipilimumab. The secondary objectives are to estimate the progression free survival (PFS) of pooled mutant-KRAS long peptide vaccine with poly-ICLC adjuvant in combination with chemoimmunotherapy, Nivolumab + Ipilimumab for the first line treatment of patients with unresectable Stage III/IV NSCLC whose tumors harbor selected KRAS mutations (KRAS glycine-to-cysteine substitution at codon 12 (G12C), KRAS glycine-to-valine substitution at codon 12 (G12V), KRAS glycine-to-aspartate substitution at codon 12 (G12D), KRAS glycine-to-arginine substitution at codon 12 (G12A), KRAS glycine-to-Aspartate "D" at codon 13 (G13D) or KRAS G12R) and to assess the impact of predicted KRAS mutations on mutant-KRAS specific T cell responses in the peripheral blood of these patients. Participants will receive two doses of chemoimmunotherapy followed by KRAS-targeted vaccine with ipilimumab and nivolumab. Exploratory objectives will assess the impact of predicted KRAS mutations on mutant-KRAS specific T cell responses in the peripheral blood, as well as changes in circulating tumor deoxyribonucleic acid (ctDNA). Approximately 15 subjects will be enrolled to have 12 evaluable subjects for T cell response assessment. Safety analysis will include all enrolled patients who receive at least one dose of vaccine. The evaluable population for T cell response will consist of all patients who receive at least one dose of vaccine and have baseline and post-treatment T cell measures in the peripheral blood at 12 weeks.
Check if I qualifyExtracted eligibility criteria
Cancer type
Non-Small Cell Lung Carcinoma
Biomarker criteria
Required: KRAS g12a
Required: KRAS g12c
Required: KRAS g12d
Required: KRAS g12r
Required: KRAS g12v
Required: KRAS g13d
Disease stage
Required: Stage III, IV (AJCC version 9)
Metastatic disease required
locally advanced/unresectable or metastatic as per AJCC version 9
Performance status
ECOG 0–1(Restricted strenuous activity)
Prior therapy
Cannot have received: immunotherapy (IL-2, interferon, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4, anti-LAG-3)
Exception: Patients who have received anti-PD(L)-1 therapy (i.e. durvalumab, atezolizumab, nivolumab) for early-stage disease with curative intent may be enrolled, so long as progressive disease occurred at least 6 months from the start of anti-PD(L)-1 therapy.
Patients with a history of prior treatment with immunotherapy agents (including, but not limited to: IL-2, interferon, anti-PD-L2, anti-CD137, anti-OX-40, anti-CD40, anti-CTLA-4, or anti-LAG-3 antibodies). Patients who have received anti-PD(L)-1 therapy (i.e. durvalumab, atezolizumab, nivolumab) for early-stage disease with curative intent may be enrolled, so long as progressive disease occurred at least 6 months from the start of anti-PD(L)-1 therapy.
Cannot have received: anti-PD-1 therapy (durvalumab, atezolizumab, nivolumab)
Exception: for early-stage disease with curative intent, allowed if progression occurred at least 6 months from start of anti-PD(L)-1 therapy
Patients who have received anti-PD(L)-1 therapy (i.e. durvalumab, atezolizumab, nivolumab) for early-stage disease with curative intent may be enrolled, so long as progressive disease occurred at least 6 months from the start of anti-PD(L)-1 therapy.
Cannot have received: chemotherapy
Chemotherapy within 2 weeks prior to initiation of study treatment
Cannot have received: systemic or localized antineoplastic therapy
Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study
Cannot have received: systemic or topical corticosteroids at immunosuppressive doses
Exception: Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
Systemic or topical corticosteroids at immunosuppressive doses (> 10 mg/day of prednisone or equivalent). Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
Cannot have received: palliative or adjuvant radiation or gamma knife radiosurgery
Palliative or adjuvant radiation or gamma knife radiosurgery within 2 weeks prior to initiation of study treatment
Cannot have received: investigational cytotoxic drug
Any investigational cytotoxic drug. Exposure to any cytotoxic drug within 4 weeks or 5 half-lives (whichever is shorter) is prohibited.
Cannot have received: investigational device
Any investigational device within 4 weeks prior to initiation of study treatment
Cannot have received: non-oncology vaccines containing live virus (measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, typhoid vaccine)
Exception: Influenza, pneumonia vaccines (polysaccharide and conjugated forms) and COVID-19 vaccines allowed, but recommend not within 7 days before or after KRAS peptide vaccination.
Non-oncology vaccines containing live virus. Examples include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid vaccine. Influenza, pneumonia vaccines (polysaccharide and conjugated forms) and COVID-19 vaccines will be allowed, however we recommend that subjects not receive any dose of vaccine within 7 days before or after their scheduled KRAS peptide vaccination.
Cannot have received: allergen hyposensitization therapy
Allergen hyposensitization therapy within 4 weeks prior to initiation of study treatment
Cannot have received: growth factors (granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin)
Growth factors, e.g. granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin within 4 weeks prior to initiation of study treatment
Cannot have received: major surgery
Exception: excludes celiac plexus block, biliary stent placement, and other minor procedures such as dental work, skin biopsy, etc.
Major surgery (excludes celiac plexus block, biliary stent placement, and other minor procedures such as dental work, skin biopsy, etc.)
Lab requirements
Blood counts
Leukocytes ≥ 3,000/mcL; Absolute neutrophil count ≥ 1,000/mcL; Platelets ≥ 75 × 10^3/uL; Hemoglobin ≥ 8.0 g/dL
Kidney function
Creatinine ≤1.5 × ULN or creatinine clearance (CrCl) ≥ 40 mL/min (Cockcroft-Gault formula)
Liver function
Total bilirubin ≤ 1.5 x ULN (< 2.0 x ULN for subjects with documented Gilbert's syndrome); AST(SGOT) and ALT(SGPT) ≤ 2.5 × ULN (if liver metastases are present, ≤ 5 x ULN); Alkaline phosphatase ≤5.0 × ULN
Patients must have adequate organ and marrow function as defined below: Leukocytes ≥ 3,000/mcL; Absolute neutrophil count ≥ 1,000/mcL; Platelets ≥ 75 × 10^3/uL; Hemoglobin ≥ 8.0 g/dL; Total bilirubin ≤ 1.5 x ULN (< 2.0 x ULN for subjects with documented Gilbert's syndrome); AST(SGOT) and ALT(SGPT) ≤ 2.5 × ULN (if liver metastases are present, ≤ 5 x ULN); Alkaline phosphatase ≤5.0 × ULN; Creatinine ≤1.5 × ULN or creatinine clearance (CrCl) ≥ 40 mL/min (Cockcroft-Gault formula)
Structured fields extracted by AI. May contain errors — verify against the official protocol.
US trial sites
- Johns Hopkins University · Baltimore, Maryland
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