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

NCT05254184 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: J21131IRB00306311
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Non-Small Cell Lung Cancer

Keywords

Advanced KRAS mutated Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Safety of administering a KRAS peptide vaccine in combination with chemoimmunotherapy, nivolumab and ipilimumab as assessed by adverse events.

  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

  Up to day 29

• Feasibility of administering a KRAS peptide vaccine in combination with chemoimmunotherapy, nivolumab and ipilimumab as assessed by adverse events.

  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

  Up to 29 days

Secondary Outcomes (3)

• Progression Free Survival (PFS) as assessed by imaging

  Baseline to progression, up to 4 years

• Change in interferon-producing mutant-KRAS-specific cluster of differentiation (CD) 8 T cells in the peripheral blood

  Pre-vaccination baseline to end of treatment, up to 2 years

• Change in interferon-producing mutant-KRAS-specific CD 4 T cells in the peripheral blood

  Pre-vaccination baseline to end of treatment, up to 2 years

Study Arms (1)

Patients With NSCLC

EXPERIMENTAL

All participants will receive the intervention.

Drug: Pooled Mutant KRAS-Targeted Long Peptide Vaccine 0.3mg each; 1.8mg total peptides

Interventions

Pooled Mutant KRAS-Targeted Long Peptide Vaccine 0.3mg each; 1.8mg total peptides DRUG

administering the KRAS peptide vaccine with poly-ICLC adjuvant in combination with chemoimmunotherapy, nivolumab and ipilimumab

Also known as: Nivolumab 3 mg/kg every 2 weeks, Ipilimumab 1 mg/kg every 6 weeks, Carboplatin AUC 4 or 5 every 3 weeks, Paclitaxel 175 mg/m2 or 200 mg/m2 every 3 weeks, Pemetrexed 500 mg/m2 every 3 weeks

Patients With NSCLC

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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
• 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):
• o Female CrCl = (140 - age in years) x weight in kg x 0.85

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.
• 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.

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead

Study Sites (1)

Johns Hopkins University

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab; Ipilimumab; Paclitaxel; Pemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• Kristen Marrone, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristen Marrone, MD

CONTACT

410-955-8964; ThoracicCancerTrials@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: February 24, 2022
• Study Start: November 1, 2022
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)