Summary
Researchers presented positive final data from a phase I/II study of PolyPEPI1018, an off-the-shelf multi-peptide treatment, in microsatellite stable metastatic colorectal cancer (MSS mCRC) patients during an online poster presentation at the 2020 ASCO Annual Meeting (Abstract 4048).
“The study showed that 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,” explained principal investigator Joleen Hubbard, MD, Associate Professor Medical Oncology at the Mayo Clinic Rochester and a gastrointestinal oncologist. “Importantly, a patient’s immunological and clinical responses could be predicted using a simple buccal cheek swab test, negating the need for a tumor biopsy to identify potential responders.”
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Original Article
Positive Results for Off-the-Shelf Metastatic CRC Immunotherapy
Oncology Times
Researchers presented positive final data from a phase I/II study of PolyPEPI1018, an off-the-shelf multi-peptide treatment, in microsatellite stable metastatic colorectal cancer (MSS mCRC) patients during an online poster presentation at the 2020 ASCO Annual Meeting (Abstract 4048).
“The study showed that 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,” explained principal investigator Joleen Hubbard, MD, Associate Professor Medical Oncology at the Mayo Clinic Rochester and a gastrointestinal oncologist. “Importantly, a patient’s immunological and clinical responses could be predicted using a simple buccal cheek swab test, negating the need for a tumor biopsy to identify potential responders.”
PolyPEPI1018 is an off-the-shelf, synthetic, long peptide treatment containing immunogenic fragments of seven conserved cancer-testis antigens (CTAs) frequently expressed in mCRC. PolyPEPI1018 was designed to induce polyvalent T-cell responses in a large subpopulation of CRC patients using a computational tool that identifies personal epitopes that are likely to induce antigen-specific T-cell responses in a subject.
Study Details
The phase I/II OBERTO study was an open-label, single-arm, multicenter study to evaluate the safety, tolerability, immunogenicity, and preliminary efficacy of a single dose or of multiple doses of PolyPEPI1018 as an add-on to fluoropyrimidine/bevacizumab maintenance therapy in MSS mCRC patients after first-line induction chemotherapy (NCT03391232).
In the trial, 11 patients with MSS mCRC were injected subcutaneously with PolyPEPI1018 just after their planned transition to maintenance therapy with fluoropyrimidine/bevacizumab following the use of first-line combo chemotherapy and bevacizumab. The first part of the study included five patients who received a single dose of the immunotherapy within 21 days of transitioning to maintenance therapy. The second part included six patients who received three doses of the immunotherapy every 12 weeks. The primary endpoint was safety. The study showed that PolyPEPI1018 was safe and well-tolerated. It also produced a robust immune response against multiple tumor antigens.
Seven out of the 10 immune-evaluable patients had pre-existing immune responses against multiple targeted antigens, confirming the expression of target CTAs on the surface of the tumors. All pre-existing immune responses significantly boosted by the treatment. De novo antigen-specific t-cell responses were also induced against multiple antigens for eight out of 10 patients. Repeated treatments increased the magnitude of T-cell responses.
Multi-antigenic CD8+ T-cell responses were detected for 80 percent of patients, exceeding the immune response rates reported for personalized neoantigen immunotherapies. Anticancer immunity was demonstrated to be HLA-genotype dependent, which predicted treatment benefit. Among four patients who had serial liver biopsies performed, increased immune cell infiltration was detected, which confirmed the conversion of previously immunologically cold tumors into hot tumors.
Immune responses induced by PolyPEPI1018 both at the peripheral and the tumor level indicate tumor response. Maintenance therapy, combined with multiple doses of PolyPEPI1018, led to objective responses and improved progression-free survival (PFS) for MSS mCRC patients. The median progression free survival (mPFS) in the multiple-dose group of 12.5 months compares favorably to results published from a recent trial conducted elsewhere in a relevant, large cohort using the same maintenance therapy but without an add-on immunotherapy (mPFS =7.4 months).
The poster also included details on two patients previously determined to have unresectable disease who responded so well to the treatment with PolyPEPI1018 that each of the two patients was able to undergo curative resection.