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An investigational therapeutic vaccine appeared to be effective in delaying relapse of KRAS-mutated pancreatic and colorectal cancer (CRC), according to results from the phase I AMPLIFY-201 study.

Among 25 patients with pancreatic ductal adenocarcinoma (PDAC) and CRC who were considered at high risk for relapse and who received a maximum of 10 doses of the ELI-002 vaccine targeted toward KRAS G12D and G12R mutations, T-cell responses occurred in 84%, and in 100% of those in the two highest dose cohorts, reported Shubham Pant, MD, MBBS, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues.

Furthermore, T-cell response correlated with an 86% reduction in risk of relapse or death, they noted in .

"Overall, this study provides important proof of concept for the safety and immunogenicity of lymph-node-targeting Amph [Amphiphile] vaccines and yielded promising signals of clinical activity that correlates with the magnitude of ELI-02 2P-induced T cell response," the authors wrote.

"Pancreatic cancer patients, even after resection, have a high risk of relapse even after adjuvant therapy," Pant told 乌鸦传媒. "So this is an area of unmet need."

These results "are early, but promising," he added. "If this is validated in a bigger trial, we are truly moving the needle in these patients, especially those with pancreatic cancer."

ELI-002 is composed of AMP-modified mutant KRAS peptide antigens and ELI-004 -- an AMP-modified immune-stimulatory oligonucleotide CpG adjuvant available as an off-the-shelf subcutaneous administration. Pant explained that what distinguishes ELI-oo2 as a vaccine is that it is directed into lymph nodes in order to elicit more robust immune responses and target mutant KRAS with greater potency and precision.

Of the 25 patients (median age 61 years, 60% women), 20 had pancreatic cancer and five had CRC. Of these patients, 84% were white, 8% were Asian, and the remainder had unreported ethnicity. All 25 previously had surgery or another procedure designed to be curative, and seven previously had received radiation therapy.

The vaccine was evaluated at dose levels of 0.1, 0.5, 2.5, 5, and 10 mg. T-cell responses were observed in 21 of the 25 patients, and at the two highest dose levels, all patients (11 of 11) demonstrated elevated mutant KRAS-specific T-cell responses following ELI-002 vaccination.

Pant and colleagues observed that efficacy correlated with T-cell responses above or below the median-fold increase (12.75-fold) over baseline. Above-median T-cell response correlated with biomarker-assessed clinical antitumor activity, with a median change from baseline in tumor biomarker of -76% versus -10.2% in those patients with a below-median T-cell response (P<0.0014).

Among the 13 above-median T-cell responders, 100% showed biomarker reduction, with six achieving biomarker clearance. None of the 12 with below-median T-cell response achieved clearance, while eight showed reduction.

These findings further correlated to relapse-free survival (RFS). At at median follow-up of 8.5 months, the median RFS for the entire study cohort was 16.33 months, with the median RFS was not reached among above-median T-cell responders compared with 4.01 months in below-median T-cell responders, translating into an 86% reduced risk of relapse or death (HR 0.14, 95% CI 0.03-0.63, P=0.0167).

Regarding safety, 12 patients experienced an adverse event related to the vaccine, all grade 1 or grade 2. There were no reported cases of cytokine release syndrome and no dose-limiting toxicities. The most common adverse events of any grade were fatigue (24%), injection site reaction (16%), and myalgia (12%).

One serious adverse event was reported: a grade 3 abdominal wall hematoma that resolved 8 days after onset and was considered related to a biopsy performed per protocol to confirm progression. No events led to discontinuation of treatment or death.

Pant noted that a potential advantage of ELI-002 is its availability as an off-the-shelf therapy.

"Recently, individualized neoantigen cancer vaccines have shown promising efficacy for PDAC, non-small cell lung cancer, colorectal cancer, and melanoma," the authors wrote. "The availability of ELI-002 as an 'off-the-shelf' product offers several further advantages, including streamlined standard manufacturing to facilitate on-demand availability while eliminating the need for tumor-informed production, which presents operational risks and limits use to post-surgical adjuvant stage."

Results from this trial have led to a that will begin later this year, Pant noted, with a new formulation of ELI-002 that will target seven of the most common KRAS mutations.

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