Metastatic Colorectal Cancer Vaccine Candidate Displays Positive Results

Treos Bio PolyPEPI1018 is an add-on to maintenance therapy in patients with microsatellite-stable metastatic colorectal cancer
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(Precision Vaccinations)

London-based Treos Bio Limited reported updated positive results on the second part of its phase 1/2 study with the PolyPEPI1018 cancer vaccine.

This small colon cancer vaccine study is researching PolyPEPI1018 as an add-on to maintenance therapy in patients with microsatellite-stable (MSS) metastatic colorectal cancer (mCRC).

PolyPEPI1018 is an off-the-shelf, synthetic long peptide vaccine containing immunogenic fragments of 7 conserved cancer-testis antigens (CTAs) frequently expressed in mCRC. 

Last updated on September 11, 2019, this phase 1/2 study is an open-label, single-arm, multicenter study to evaluate the safety, tolerability, immunogenicity and preliminary efficacy of single-dose (first part of the study) or multiple doses (second part of the study) of PolyPEPI1018 as an add-on to maintenance therapy in patients with metastatic colorectal cancer, after first-line induction chemotherapy.

mCRC patients in first-line setting received up to 3 doses of PolyPEPI1018 vaccine (0.2 mg/peptide) 12 weeks apart, just after the transition to maintenance therapy with fluoropyrimidine and bevacizumab. Eleven patients were vaccinated with PolyPEPI1018. 

Vaccine-specific T cell responses were first predicted by PEPI test (using the patient’s complete HLA genotype) then measured after one cycle of vaccination.

The vaccine was found well tolerated; common adverse events were transient skin reactions and flu-like syndrome. No grade 3+ adverse events related to the vaccine occurred. 

A total of 80 percent of patients had CD8+ T cell responses against at least three of the seven vaccine antigens, and ex vivo responses (both CD8 and CD4) could be detected in almost 90 percent of evaluated patients. 

Circulating vaccine-induced polyfunctional T cells were detected after a single dose and their frequency increased after multiple vaccinations. PEPI test correctly predicted ELISpot-measured CD8+ T cell responses.

Previously reported objective tumor responses observed after 12 weeks of administering a single dose were maintained during the whole 38-week period of the study. 

Of the 5 patients who received at least 2-doses of the vaccine, 3 experienced Stable Disease and 2 had unexpected tumor size reduction of whom one patient experienced complete tumor shrinkage on two of three target lesions and partial response on one lesion. 

Patients experiencing tumor shrinkage had a higher number of predicted antigens than those without tumor response.

“Besides the unexpected tumor responses observed for some of the patients, it is very encouraging that the majority of patients on multiple doses controlled their disease until the end of the follow-up period and beyond,” said Joleen M. Hubbard M.D., principal investigator of the OBERTO trial at the Mayo Clinic. 

“We plan to continue enrollment of further patients in the study and follow them for an even longer period this time.”

Dr. Eniko R. Toke, Chief Scientific Officer of Treos Bio, said in a press release, “We are very excited by the potential of PEPIs as candidate genetic biomarkers in the development of highly immunogenic vaccines for a range of cancer indications and for the prediction of individuals’ immunogenetic risk of developing cancer.”

The full study abstract is available here. And, the oral presentation will be available at Treos Bio on September 30, 2019.

Colorectal cancer is the third most common cancer worldwide, accounting for one-third of the cancer incidence and mortality burden worldwide together with lung and breast cancers with nearly 881,000 deaths in 2018 from colorectal cancer worldwide, according to GLOBOCAN. 

While improvements in cancer care have boosted survival rates for all stages of colorectal cancer in the past two decades, the prognosis for patients with metastatic colorectal cancer remains grim. 

The 5-year relative survival rate for patients with metastatic colon cancer is just 14 percent. For patients with metastatic rectal cancer, the 5-year relative survival rate is just 15 percent, according to the American Cancer Society.

Treos Bio, headquartered in London, uses data science and proprietary biomarkers to develop its precision cancer vaccines, with substantially shortened development timelines and at lower costs.

Cancer Vaccine news published by Precision Vaccinations