KRAS-Targeted Vaccine With Chemoimmunotherapy, Nivolumab and Ipilimumab for Patients With NSCLC
Eligible age
18–100 yrs
Accepts
All genders
Locations
1 state
Healthy volunteers
No
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About this study
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.
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
You may qualify if…
- ✓ Histologically- or cytologically-proven non-small cell lung cancer deemed to be locally advanced/unresectable or metastatic as per AJCC version 9, who has not received prior therapy for this stage of disease.
- ✓ Must have tumor lesions amenable to repeated biopsy, and patient's acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the Principal Investigator).
- ✓ Measurable disease as defined by RECIST v1.1.
- ✓ Have one of the KRAS mutations (KRASG12C, KRASG12V, KRASG12D, KRASG12A, KRASG13D or KRASG12R) included in the vaccine at the time of vaccination expressed in tumor as defined by a CLIA-certified tumor or plasma based genomic testing platform performed either through a local laboratory or through our central laboratory.
- ✓ ECOG performance status 0 or 1.
- ✓ Patients must have adequate organ and marrow function as defined below:
- ✓ Leukocytes ≥ 3,000/mcL
- ✓ Absolute neutrophil count ≥ 1,000/mcL
You may not qualify if…
- ✕ Patient is expected to require any other form of systemic or localized antineoplastic therapy while on study.
- ✕ Any of the following procedures or medications:
- ✕ Within 2 weeks prior to initiation of study treatment:
- ✕ 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.
- ✕ Palliative or adjuvant radiation or gamma knife radiosurgery.
- ✕ Chemotherapy
- ✕ Within 4 weeks prior to initiation of study treatment:
- ✕ Any investigational cytotoxic drug. Exposure to any cytotoxic drug within 4 weeks or 5 half-lives (whichever is shorter) is prohibited. If 5 half-lives are shorter than 4 weeks, agreement with IND Sponsor is mandatory.
Where it's recruiting
Baltimore
Source: ClinicalTrials.gov · NCT05254184 · last updated 2026-03-30