Colorectal Cancer Vaccine Candidate Induces Potent Immune Responses, Interim Trial Results Show

A single dose of PolyPEPI1018 — Treos Bio’s investigational off-the-shelf vaccine for colorectal cancer — induced promising immune responses and clinical signs of efficacy when given in combination with standard maintenance therapy in metastatic colorectal cancer patients, interim results from a Phase 1/2 trial show.

The findings from the company’s first-in-human trial were presented June 3 at the 2019 American Society of Clinical Oncology Annual Meeting in Chicago, in a poster titled “A phase I study of PolyPEPI1018 vaccine plus maintenance therapy in patients with metastatic colorectal cancer with a predictive biomarker (OBERTO).”

PolyPEPI1018 is an off-the-shelf cancer vaccine consisting of six synthetic protein fragments that induce immune responses against seven proteins commonly found in colorectal cancer cells, thereby producing long-lasting responses against colorectal tumors, while sparing healthy cells. Because the immune system becomes primed for several cancer proteins, the vaccine is able to target multiple cancer cells.

The OBERTO Phase 1/2 trial (NCT03391232) — ongoing at the Mayo Clinic in Rochester, Minnesota, and at the University of Pisa in Italy — was designed to test the vaccine as an add-on to standard maintenance treatment for metastatic colorectal cancer.

To be eligible, participants must have not seen their disease progress after receiving first-line chemotherapy and biological therapy for their metastatic condition.

OBERTO’s primary goal is to determine the safety and tolerability of PolyPEPI1018, but researchers will also assess T-cell responses and preliminary efficacy as secondary endpoints.

The trial runs in two parts. In the first part, participants will receive a single dose of the vaccine, followed by a 12-week follow-up period. In the second part, they’ll receive three doses of the vaccine, given 12 weeks apart.

To date, 11 patients have been vaccinated with a single dose of PolyPEPI1018 just after transitioning into maintenance therapy with Avastin (bevacizumab) and the chemotherapy fluoropyrimidine.

The treatment was found to be safe and well-tolerated, with no serious adverse events, and all patients developed immune responses derived from PolyPEPI1018. The researchers said that a single shot of PolyPEPI1018 led to “unprecedented immunological activity,” with T-cells targeting up to five cancer proteins per patient.

They report that the immune reaction triggered by PolyPEPI1018 outperformed that of personalized vaccines and led to durable responses when given as an add-on to maintenance therapy.

Based on these findings, the trial has been amended to treat patients with three doses of the vaccine, given 12 weeks apart.

“Despite the single dose of PolyPEPI1018, we have seen unexpected clinical signals in the first part of the study: of the 11 vaccinated patients, three had progressed disease, five of them had stable disease and three of them experienced partial tumor remission, one of them qualifying for curative surgery,” Joleen M. Hubbard, MD, the principal investigator of the OBERTO trial at the Mayo Clinic, said in a press release.

“This is the first presentation of clinical data from this program at a major medical conference and we plan to share updated data from this study later this year,” Hubbard added.

Treos Bios has also developed a diagnostic test to identify patients who are likely to benefit from the vaccine. The PEPI Test uses genetic data obtained from a saliva or blood sample to predict how each patient’s immune system will respond to the synthetic proteins in the vaccine.

Results from the trial have shown that the test correctly predicted responses in 71% of cases.

“We obtained very encouraging clinical results in terms of patient responses and the ability of the PEPI Test to predict responses in line with our pre-clinical data, which support further development of PolyPEPI1018 together with candidate companion diagnostics for the selection of likely responders,” said Eniko R. Toke, chief scientific officer of Treos Bio.

Results of the second part of the trial are expected by year’s end.