The PolyPEPI1018 vaccine, when given with the immunotherapy drug, Tecentriq (atezolizumab), induced immune responses against tumors in a small group of patients with relapsed or refractory microsatellite-stable (MSS) metastatic colorectal cancer (CRC), according to findings from the phase 2 Oberto-301 trial that were presented at the 2024 American Society of Clinical Oncology Annual Meeting.
The majority of CRC cases are MSS, meaning that they don’t have certain DNA mutations that are involved with how cells are replicated. MSS cancers often do not trigger a response from the immune system.
Study Highlights:
- The combination of PolyPEPI1018 and Tecentriq is being studied for certain patients with metastatic colorectal cancer.
- Patients who had a strong immune response to the treatment tended to live longer on this regimen.
- The treatment did not result in any objective responses (tumors shrinking or disappearing) but showed a disease control rate of 61%.
Data showed no serious side effects during study treatment. Overall, 18 patients had 58 mild side effects and 18 moderate side effects in eight patients; no severe side effects occurred. Common mild events included injection site reactions (21 patients), fatigue (seven patients) and headache (four patients). The most frequent moderate side effects were blood alkaline phosphate increases, which can indicate liver, bone or other complications (two patients), nausea (two patients) and fever (two patients).
The median progression-free survival (PFS; time patients live until disease worsening) across the overall population was 12 weeks, and the median overall survival (OS; time until death of any cause) was 55 weeks. Regarding median OS, investigators reported no significant differences in outcomes between patients with liver metastases (37 months) and those without metastases (71 months). When there is no statistically significant difference, that indicates that the researchers cannot be sure if the treatment truly led to an improved outcome.
A longer median OS was highlighted in those who had a robust T cell response (meaning that immune T cells were activated against the tumor) compared with those who had a weak immune response (47 months).
Treatment yielded an objective response rate (ORR; percentage of patients whose disease shrunk or disappeared) of 0% and a disease control rate of 61%.
Findings highlighted a significant increase in tumor-infiltrating lymphocyte (TIL; white blood cells that identify and kill cancer) density based on post-treatment biopsies as well as a significant expansion of PD-L1 expression. PD-L1 is a protein found on cancer cells that help them hide from the immune system. Tecentriq works by blocking PD-L1.
Additionally, an analysis conducted outside of the body indicated CD8 and CD4 responses, and antigen-specific humoral responses (when the body creates antigens in response to a vaccine) were also observed.
“Despite no ORR detected, consistent immunological and clinical efficacy data indicate an anti-tumor effect of the combination,” Dr. Joleen M. Hubbard, deputy director for Clinical Research at Alina Health Cancer Institute, and coauthors wrote in the poster. “These data indicate that vaccination with PolyPEPI1018 may augment the efficacy of [Tecentriq] in MSS [metastatic] CRC and merit confirmation in a randomized trial.”
In this multi-center, open-label, phase 2 trial, patients who previously progressed on prior lines of chemotherapy were assigned to receive PolyPEPI1018 plus Tecentriq until progressive disease or unacceptable side effects. Investigators administered vaccines to four anatomical sites for each dose.
The trial’s primary end point (main result measured at the end of the study) was safety and tolerability. Secondary end points included ORR, PFS, OS, immune-related markers, TIL and PD-L1 expression changes, and clinical-marker correlations with human leukocyte antigen (HLA) status.
Patients with measurable MSS metastatic CRC who had two or three prior lines of treatment for advanced or metastatic disease were eligible for enrollment on the study. Other requirements for study entry included having documented radiographic progression following the last line of therapy; an ECOG performance status of 0 or 1 (which indicates that they can perform all of their daily tasks independently); and no prior therapy with anti–CTLA-4, anti-PD-1, anti-PD-L1 or anti-PD-L2 agents.
Of 18 patients who enrolled on the stage 1 portion of the study, the median age was 54 years, and most were female (66.7%). Additionally, most patients were White (61.1%), had liver (44.4%) or lung lesions (44.4%), three prior lines of therapy (66.7%), an ECOG performance status of 0 (no restrictions on daily activity; 55.6%), and KRAS mutations (55.6%). Anatomical locations included the transverse colon (16.7%) and left colon (11.1%), although most patients had disease in other anatomical locations (61.1%).
Post-treatment TIL density showed a significant correlation with PFS. Additionally, PD-L1 levels after treatment were associated with PFS.
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