NCT07004244

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

Safety and Efficacy of KRAS Vaccine in the Treatment of KRAS-mutant Malignancies

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Sichuan University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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

Detailed description

The Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most prevalent oncogenes in humans and plays a pivotal role in tumor initiation and progression. KRAS mutations are observed in various cancers, particularly in non-small cell lung cancer, colorectal cancer, and pancreatic cancer. Mutations in the KRAS gene activate multiple signaling pathways, such as MAPK/ERK and PI3K/AKT, which regulate cell proliferation, survival, and migration, thereby driving tumor progression and the development of drug resistance. Due to its critical role in cancer, KRAS has emerged as a key therapeutic target. However, the structural characteristics of KRAS mutants have historically rendered direct inhibition of the KRAS protein extremely challenging, leading to its designation as an "undruggable" target over the past decades. Consequently, patients with KRAS-mutated malignancies face limited treatment efficacy and a lack of precision therapeutic options. In recent years, advances in scientific technologies have enabled the successful development and marketing of several drugs targeting specific KRAS mutations. Nevertheless, most existing therapies exhibit suboptimal efficacy, necessitating further exploration of treatments for broader mutation types and larger cancer populations. mRNA vaccines represent a highly promising novel approach in oncology. Preliminary reviews of global clinical trials investigating tumor-related mRNA therapeutics reveal that current research primarily focuses on malignancies such as melanoma, prostate cancer, colorectal cancer, acute myeloid leukemia, and breast cancer, with most studies in Phase I/II. Published data demonstrate that mRNA-based cancer therapies exhibit significant potential in anticancer immunotherapy and favorable safety profiles. Given the promising antitumor efficacy of mRNA therapeutic vaccines targeting KRAS mutations in KRAS-mutated tumors, coupled with the limited treatment options and poor outcomes for most KRAS-mutated cancer patients, monotherapy with mRNA therapeutic vaccines or their combination with immune checkpoint inhibitors may offer substantial clinical benefits. Accordingly, the research team plans to conduct an "Exploratory Study on the Application of mRNA Vaccines Targeting KRAS Mutations in KRAS-Mutated Malignancies."

Conditions

• Malignant Tumors

Interventions

Type	Name	Description
BIOLOGICAL	KRAS-mutated mRNA vaccine	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
BIOLOGICAL	TORIPALIMAB	intravenous injection
DRUG	Pemetrexed+carboplatin	intravenous injection

Timeline

• Start date: 2025-06-05
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2025-06-04
• Last updated: 2025-06-24

Locations

1 site across 1 country: China