Actively Recruiting

Phase 1
Age: 18Years - 100Years
All Genders
NCT05254184

KRAS-Targeted Vaccine With Chemoimmunotherapy, Nivolumab and Ipilimumab for Patients With NSCLC

Led by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Updated on 2026-03-30

12

Participants Needed

1

Research Sites

230 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

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.

CONDITIONS

Official Title

KRAS-Targeted Vaccine With Chemoimmunotherapy, Nivolumab and Ipilimumab for Patients With NSCLC

Who Can Participate

Age: 18Years - 100Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Histologically or cytologically confirmed non-small cell lung cancer that is locally advanced, unresectable, or metastatic, with no prior therapy for this stage
  • Tumor lesions suitable for repeated biopsy and willingness to undergo biopsy at baseline and during treatment if safe
  • Measurable disease according to RECIST v1.1 criteria
  • Presence of one of the KRAS mutations (G12C, G12V, G12D, G12A, G13D, or G12R) in the tumor confirmed by certified genomic testing
  • ECOG performance status of 0 or 1
  • Adequate organ and marrow function as defined by specific blood count and liver and kidney function thresholds
  • Negative pregnancy test for women of childbearing potential
  • Agreement to use contraception during and after study treatment as specified
  • Ability to understand and sign informed consent
Not Eligible

You will not qualify if you...

  • Requirement for any other systemic or localized cancer therapy while on study
  • Use of systemic or topical immunosuppressive corticosteroids or chemotherapy within specified recent time frames
  • Recent use of investigational cytotoxic drugs or devices
  • Receipt of live virus vaccines recently; influenza, pneumonia, and COVID-19 vaccines allowed with timing recommendations
  • Prior treatment with immunotherapy agents or certain anti-PD(L)-1 therapies that do not meet specific conditions
  • History of severe allergic reactions to monoclonal antibodies or related compounds
  • Untreated or symptomatic brain metastases; treated brain metastases allowed if stable
  • Active autoimmune disease requiring systemic treatment within 2 years, with some exceptions
  • Known interstitial lung disease or pneumonitis requiring steroids
  • Low oxygen saturation or need for home oxygen
  • Infection with HIV, hepatitis B or C
  • Uncontrolled illnesses or psychiatric conditions limiting study compliance
  • Recent diagnosis of other cancers except certain low-risk types
  • Immunodeficiency or history of organ or stem cell transplant
  • Substance abuse or inability to follow study schedule
  • Pregnancy or breastfeeding

AI-Screening

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Trial Site Locations

Total: 1 location

1

Johns Hopkins University

Baltimore, Maryland, United States, 21287

Actively Recruiting

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Research Team

K

Kristen Marrone, MD

CONTACT

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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