Treos Bio's PolyPEPI1018 Combined with Tecentriq Shows Promising Survival Signals in Phase 2 Trial
Clinical Design and Progress
The OBERTO-301 trial by Treos Bio Limited is an open-label, single-arm Phase 2 clinical trial evaluating patients with microsatellite-stable metastatic colorectal cancer (MSS mCRC) who have progressed after two to three prior lines of therapy. Eighteen patients were enrolled and received PolyPEPI1018 1.2mg subcutaneously and Roche's Tecentriq (atezolizumab) 1,200mg intravenously every three weeks. The primary completion date was July 8, 2024, and enrollment is closed, but survival follow-up is ongoing. As it is a Simon 2-stage design without a randomized control arm, a subsequent confirmatory trial is needed to determine efficacy.
Drug and Immunological Rationale
PolyPEPI1018 is an off-the-shelf, multi-antigen cancer vaccine in Phase 2 clinical development, composed of six synthetic peptides targeting 12 immunodominant epitopes of seven colorectal cancer-associated tumor antigens. It aims to induce a multi-specific T-cell response tailored to the patient's human leukocyte antigen (HLA) genotype, converting immunologically 'cold' tumors into inflamed 'hot' tumors. Tecentriq is an approved anti-PD-L1 antibody that supports the tumor-specific T-cells generated by the vaccine, preventing them from being suppressed by immune checkpoint signals. Tecentriq was first approved in the United States on May 18, 2016, but there is no approved indication for MSS colorectal cancer, making this combination a developmental strategy.
Interpretation of Clinical Signals
At ASCO 2024, the median overall survival was 12.8 months, and the 12-month survival rate was 60%, with no serious treatment-related adverse events or new toxicity signals reported. The company presented historical data from a similar patient population treated with Tecentriq alone, which showed a median overall survival of 7.1 months and a 12-month survival rate of 27%. However, the sample size of 18 patients and the non-randomized, historical comparison do not eliminate potential biases related to patient selection, the proportion of liver metastases, or subsequent treatments. Therefore, while the survival signals are meaningful for proof-of-concept, they are not yet at a stage where they can be interpreted as definitive efficacy.
Market and Competitive Landscape
MSS accounts for approximately 96% of metastatic colorectal cancer cases and represents a large unmet need, as existing PD-1/PD-L1 monotherapies have limited efficacy. The global market for colorectal cancer treatments was approximately USD 13.1 billion in 2024, and Roche's Tecentriq generated CHF 3.64 billion in total sales in the same year. Current late-line treatment standards include Lonsurf (trifluridine/tipiracil), Avastin (bevacizumab), Stivarga (regorafenib), and Fruzaqla (fruquintinib), which received FDA approval on November 8, 2023. For PolyPEPI1018 to be competitive, it needs to demonstrate improved overall survival in a controlled clinical trial and prove the value of HLA-based companion diagnostics for patient selection.
From an investment perspective, the median overall survival of 12.8 months and a 12-month survival rate of 60% in an 18-patient Phase 2 trial provide a rationale for the development of a cancer vaccine/PD-L1 combination in MSS mCRC, but the lack of a control arm limits the potential for revaluation. For researchers, this is clinical and translational data demonstrating whether PolyPEPI1018, which targets seven tumor antigens simultaneously, can convert immunologically 'cold' tumors when combined with Tecentriq. The industry benchmark is Lonsurf, Avastin, and Fruzaqla, which have Phase 3 data and FDA approval, and the target market is approximately USD 13.1 billion in 2024. Short-term catalysts include the completion of immunogenicity, response rate, and long-term survival data, while long-term value depends on entry into a randomized controlled trial and the reproducibility of patient selection through HLA companion diagnostics.
Source: ClinicalTrials.gov (api_ct)