Application of KRAS Vaccine in the Treatment of KRAS-mutated Malignancies

NCT07004244 | Recruiting Phase 1 DMC

• 1 other identifier: KRAS ST-2025
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to evaluate the safety and efficacy of mRNA vaccine for the KRAS mutation malignant tumors.

Conditions

Malignant Tumors

Keywords

KRAS-mutated malignancies; mRNA vaccines; treatment; safety; efficacy

Outcome Measures

Primary Outcomes (2)

• Adverse events

  Adverse events defined as the number of participants with adverse events according to CTCAE v5.0.

  up to 12 months

• Immunogenicity of the mRNA vaccine

  Measure vaccine-induced immune response (e.g., antigen-specific T-cell/B-cell responses or seroconversion rates).

  up to 7 months

Secondary Outcomes (5)

• Objective response rate

  up to 12 months

• Progress-Free Survival

  up to 12 months

• Overall Survival

  up to 12 months

• Pathological response rates

  up to 7 months

• Surgical feasibility

  up to 7 months

Study Arms (2)

Cohort 1

EXPERIMENTAL

From the initial dose, the dose was increased using a dose escalation scheme. Each subject only received one corresponding dose.

Biological: KRAS-mutated mRNA vaccine

Cohort 2

EXPERIMENTAL

KRAS-mutated mRNA vaccine+ Toripalimab + pemetrexed + carboplatin as neo-adjuvant treatment followed by surgery

Biological: KRAS-mutated mRNA vaccine; Biological: TORIPALIMAB; Drug: Pemetrexed+carboplatin

Interventions

KRAS-mutated mRNA vaccine BIOLOGICAL

Cohort 1:From the initial dose, the dose was increased using a dose escalation scheme. Each subject only received one corresponding dose. Cohort 2:KRAS-mutated mRNA vaccine+ Toripalimab + pemetrexed + carboplatin as neo-adjuvant treatment followed by surgery

Cohort 1; Cohort 2

TORIPALIMAB BIOLOGICAL

intravenous injection

Cohort 2

Pemetrexed+carboplatin DRUG

intravenous injection

Cohort 2

Eligibility Criteria

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

You may qualify if:

• Male or female participants ≥18 years of age.
• Participants with solid tumors confirmed to carry KRAS mutations.
• At least one measurable lesion according to RECIST 1.1 criteria.
• ECOG physical condition score: 0-1 point.
• Adequate organ and bone marrow function.
• Ability to understand and voluntarily provide written informed consent before trial participation.
• Cohort 1:
• Failure of prior standard therapy, intolerance to standard therapy, ineligibility for standard therapy, or absence of a standard treatment regimen.
• Life expectancy ≥3 months.
• Cohort 2:
• Newly diagnosed, treatment-naïve lung adenocarcinoma confirmed by pathology (histology/cytology).
• Resectable disease classified as stage IB-IIIA per AJCC 9th edition criteria.
• KRAS G12C/G12D/G12V/G13D mutation-positive by genomic testing.

You may not qualify if:

• Patients with a history of other malignancies.
• Presence of primary central nervous system (CNS) tumors, active CNS metastatic tumors, or carcinomatous meningitis, either historically or identified during screening.
• Uncontrolled moderate to massive serous cavity effusion.
• Confirmed presence of other classic gene variants.
• Known cardiac clinical symptoms or diseases that are poorly controlled.
• Unstable thrombotic events (e.g., deep vein thrombosis, arterial thrombosis, pulmonary embolism) requiring therapeutic intervention within 6 months prior to screening.
• Any active autoimmune disease or a history of autoimmune disease.
• Uncontrolled clinical disorders, psychiatric illnesses, or other significant diseases as assessed by the investigator that may interfere with informed consent, compromise interpretation of trial results, pose risks to participants, or otherwise hinder the achievement of trial objectives.
• History of interstitial pneumonia or suspected interstitial pneumonia; or pulmonary abnormalities that may interfere with the detection or management of suspected drug-related pulmonary toxicity during the trial.
• Hypersensitivity to the investigational drug (including any excipients).
• Patients who received anti-tumor therapy within 4 weeks prior to the first dose, or those with unresolved adverse reactions (except alopecia) from prior anti-tumor therapy (NCI CTCAE \> grade 1).
• Systemic use of corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressants within 14 days prior to the first dose.
• Participants who received drugs of the same class within 6 months prior to the first dose.
• Prior organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), or syphilis infection.

Sponsors & Collaborators

• Sichuan University: lead
• West China Hospital: collaborator

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (13)

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MeSH Terms

Conditions

Neoplasms

Interventions

toripalimab

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 26, 2025
• First Posted: June 4, 2025
• Study Start: June 5, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: June 24, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)