PolyPEPI1018, Treos’ lead product candidate, is an off-the-shelf immunotherapy in clinical development for treating metastatic colorectal cancer, co-developed with a candidate companion diagnostic. The therapy is developing as a first-line maintenance therapy and a third-line treatment. The companion diagnostic uses Treos’ proprietary PASCal computational tool to identify Personal EPItopes (PEPIs) likely to induce antigen-specific T-cell responses in a patient.

At the ASCO 2024 meeting investigators presented new data from OBERTO 301, a multicenter, open-label, Phase II trial evaluating the combination treatment of PolyPEPI1018 and atezolizumab in patients with MSS mCRC who have progressed on two or three prior treatments regimens. The study's primary endpoint is the incidence and severity of treatment-related adverse events. Secondary endpoints include objective response rate, duration of response, progression-free survival, and overall survival. The results were as follows:

• Treatment was safe and well-tolerated; no SAE related to treatment

• PolyPEPI1018 induced immune responses within two key compartments of the immune system; significant TME modulation

• Despite no ORR detected, consistent immunological and clinical efficacy data indicate an anti-tumor effect of the combination 

• Both mOS of 12.8 months and 12 months survival rate of 60% compare favorably to historical data of atezolizumab monotherapy of 7.1 months and 27%, respectively in a similar patient 

KOL insights

“PolyPEPI1018 treatment both reactivates existing immune responses and induces efficient tumor-directed responses against multiple specific tumor antigens expressed in the metastases of colorectal cancer, which overrides immunological tolerance and allows clinically relevant anticancer effect” – Expert Opinion.

Conclusion

Current treatments for colorectal cancer (CRC) include surgery and chemotherapy in the early stages of the disease, while later stages are treated with chemotherapy, biologics, and targeted therapies. Microsatellite stable (MSS) CRC accounts for approximately 85% of all colorectal cancers and nearly all cases of metastatic CRC (mCRC). Patients with MSS CRC do not benefit from available immunotherapies. The data from the Phase II study indicate that vaccination with PolyPEPI1018 may enhance the efficacy of atezolizumab in MSS mCRC and warrant confirmation in a randomized trial.