Multi-Peptide Vaccine Combo Shows Tolerability in Metastatic MSS CRC

“These data indicate that vaccination with PolyPEPI1018 may augment the efficacy of atezolizumab in MSS [metastatic] CRC and merit confirmation in a randomized trial," according to the study authors.

Administering PolyPEPI1018, an off-the-shelf multi-peptide vaccine, in combination with atezolizumab (Tecentriq) demonstrated tolerability and induced immune responses across a small cohort of patients with relapsed/refractory microsatellite-stable (MSS) metastatic colorectal cancer (CRC), according to findings from the phase 2 Oberto-301 study (NCT05243862) that were presented in a poster session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

Data showed no serious adverse effects (SAEs) during study treatment. Overall, 18 patients had 58 mild AEs, and 18 moderate AEs were reported in 8 patients; no severe toxicities occurred. Common mild events included injection site reactions (n = 21), fatigue (n = 7), and headache (n = 4). The most frequent moderate AEs were blood alkaline phosphate increases (n = 2), nausea (n = 2), and pyrexia (n = 2).

The median progression-free survival (PFS) across the overall population was 12 weeks (95% CI, 7-18), and the median overall survival (OS) was 55 weeks (95% CI, 38-not evaluable [NE]). Regarding median OS, investigators reported no significant differences in outcomes between patients with liver metastases (37 months; 95% CI, 14-NE)) and those without metastases (71 months; 95% CI, 47-NE; HR, 0.58; 95% CI, 0.18-1.90; P = .36). A longer median OS was highlighted in those who had a robust T cell response (NE; 95% CI, 71 months to NE) compared with those who had a weak immune response (47 months; 95% CI, 14 months to NE; HR, 0.13; 95% CI, 0.02-1.02).

Treatment yielded an objective response rate (ORR) of 0% and a disease control rate of 61%.

Findings highlighted a significant increase in tumor-infiltrating lymphocyte (TIL) density based on post-treatment biopsies as well as a significant expansion of PD-L1 expression. Additionally, ex vivo analysis indicated CD8 and CD4 responses, and antigen-specific humoral responses were also observed.

“Despite no ORR detected, consistent immunological and clinical efficacy data indicate an anti-tumor effect of the combination,” Joleen M. Hubbard, MD, 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 atezolizumab 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 2 or 3 prior lines of chemotherapy were assigned to receive PolyPEPI1018 at 1.2 mg subcutaneously plus atezolizumab at 1200 mg intravenously every 3 weeks until progressive disease or unacceptable toxicity. Investigators administered vaccines to 4 anatomical sites for each dose.

The trial’s primary end point was safety and tolerability. Secondary end points included ORR based on RECIST v1.1 criteria, PFS, OS, immune-related markers, TIL and PD-L1 expression changes, and clinical-marker correlations with HLA status.

Patients with measurable MSS metastatic CRC who had 2 to 3 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; 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%), 3 prior lines of therapy (66.7%), an ECOG performance status of 0 (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 (P = .005). Additionally, PD-L1 levels after treatment were associated with PFS (P = .0071).

Reference

Hubbard JM, Ahn DH, Jones JC, et al. A phase II, multicenter, open-label study of polyPEPI1018 in combination with atezolizumab in participants with relapsed or refractory microsatellite-stable metastatic colorectal (MSS mCRC) cancer (Oberto-301). J Clin Oncol. 2024;42(suppl 16):3594. doi:10.1200/JCO.2024.42.16_suppl.3594