KRAS-Targeted Vaccine for Non-Small Cell Lung Cancer
This study is for people with advanced non-small cell lung cancer (NSCLC) that has a specific change called a KRAS mutation. It's testing a new approach that combines a KRAS-targeted vaccine with standard chemoimmunotherapy, nivolumab, and ipilimumab. The main goal is to see how safe this combination is and if it's practical to give to patients. You would be eligible if you have advanced NSCLC with a KRAS mutation and haven't had prior treatment for this stage of your disease. The study is currently unclear on its recruitment status and plans to enroll 12 participants.
- Study design
- This is a Phase 1 interventional study, meaning it's an early-stage trial focused on safety. It is a single-institution study and plans to enroll 12 participants.
- What's involved
- You would need to have tumor lesions that can be repeatedly biopsied, and you must agree to a biopsy at the start and during treatment.
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary safety and feasibility will be assessed up to 29 days after treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05254184
KRAS-Targeted Vaccine With Chemoimmunotherapy, Nivolumab and Ipilimumab for Patients With NSCLC
Recruiting
PHASE1Ages 18+InterventionalTreatmentSidney Kimmel Comprehensive Cancer Center at Johns HopkinsInvestigator-initiated
~12 participants
Updated 2026-03-30 on ClinicalTrials.gov
What's tested:Pooled Mutant KRAS-Targeted Long Peptide Vaccine 0.3mg each; 1.8mg total peptides
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Safety of administering a KRAS peptide vaccine in combination with chemoimmunotherapy, nivolumab and ipilimumab as assessed by adverse events.
Measured over Up to day 29
+1 more outcome measured
Conditions
Where it's being run
1 sites across 1 statesMaryland1
Study leadership
- Kristen Marrone, MD · PRINCIPAL_INVESTIGATOR · Johns Hopkins University
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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.
Leukocytes ≥ 3,000/mcL
Absolute neutrophil count ≥ 1,000/mcL
Platelets ≥ 75 × 103/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 (if using the Cockcroft-Gault formula below):
72 x serum creatinine in mg/dL
72 x serum creatinine in mg/dL
Women of childbearing potential (WOCBP) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin (HCG)). WOCBP is defined in Section 4.6. NOTE: If a patient has a positive or indeterminate serum or urine pregnancy test, then an ultrasound must be done to rule out pregnancy to enroll on trial.
WOCBP must agree to follow instructions for method(s) of contraception from the time of enrollment for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 4 weeks (duration of ovulatory cycle) for a total of 5 months post treatment completion.
Men who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug(s) plus 5 half-lives of study drug(s) plus 90 days (duration of sperm turnover) for a total of 7 months post-treatment completion.
At least one barrier method of contraception must be employed by all sexually active patients (male and female), regardless of other methods, to prevent the transfer of body fluids.
Ability to understand and willingness to sign a written informed consent document.
Exclusion
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.
Any investigational device
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.
Allergen hyposensitization therapy.
Growth factors, e.g. granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin
Major surgery (excludes celiac plexus block, biliary stent placement, and other minor procedures such as dental work, skin biopsy, etc.).
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. Patients with a history of immune-related adverse events secondary to prior anti-PD(L)-1 therapy will not be permitted.
History of severe hypersensitivity reaction to any monoclonal antibodies or related compounds or to any of their components (e.g., history of severe hypersensitivity reactions to drugs formulated with polysorbate 80). This includes any prior immunotherapy agents; patients having toxicity with prior anti-PD-L1 therapy requiring cessation of treatment must be excluded.
Untreated or symptomatic brain metastases.
Treated brain metastases allowed on study if asymptomatic and therapy was completed at least 2 weeks prior to treatment start, and steroid dosing outlined above.
Has an active known autoimmune disease or which has required systemic therapy in the last 2 years. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
Known history of interstitial lung disease or of (non-infectious) pneumonitis that required steroids or current pneumonitis.
Has a pulse oximetry \< 90% on room air.
Requires the use of home oxygen.
Has a known history of Human Immunodeficiency Virus (HIV) (HIV1/2 antibodies), hepatitis B, or hepatitis C infection.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness that would limit compliance with study requirements.
Patients who have been diagnosed with another cancer or myeloproliferative disorder in the past 5 years except for superficial bladder cancer, non-melanoma skin cancers, or a low-grade prostate cancer not requiring therapy.
Has a diagnosis of immunodeficiency.
Presence of any tissue or organ allograft, regardless of need for immunosuppression, including corneal allograft. Patients with a history of allogeneic hematopoietic stem cell transplant will be excluded.
Any other sound medical or psychiatric reason as determined by the Investigator.
Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements.
Patient is unwilling or unable to follow the study schedule for any reason.
Patient is pregnant or breastfeeding.
What this trial measures
- Safety of administering a KRAS peptide vaccine in combination with chemoimmunotherapy, nivolumab and ipilimumab as assessed by adverse events.Up to day 29
The safety of administering a KRAS peptide vaccine in combination with chemoimmunotherapy, nivolumab and ipilimumab will be assessed by the occurrence of the following adverse events: * Grade 3 or above drug-related toxicities * Drug-related toxicity by grade * Vaccine site reactions after KRAS injections * Nivolumab-related infusion reactions * Ipilimumab-related infusion reactions * Immune-related adverse events (AEs) * Unacceptable toxicities * Treatment-emergent changes from normal to abnormal values in key * laboratory parameters
- Feasibility of administering a KRAS peptide vaccine in combination with chemoimmunotherapy, nivolumab and ipilimumab as assessed by adverse events.Up to 29 days
Feasibility of administering a KRAS peptide vaccine in combination with chemoimmunotherapy, nivolumab and ipilimumab will be assessed by the occurrence of the following adverse events: * Grade 3 or above drug-related toxicities * Drug-related toxicity by grade * Vaccine site reactions after KRAS injections * Nivolumab-related infusion reactions * Ipilimumab-related infusion reactions * Immune-related adverse events (AEs) * Unacceptable toxicities * Treatment-emergent changes from normal to abnormal values in key * laboratory parameters