Updated survival results of ZL-IRIAN: Irinotecan plus anlotinib or in combination with penpulimab as second-line treatment of metastatic colorectal cancer.

167 Background: The irinotecan based chemotherapy in combination with bevacizumab had become the standard second-line treatment for metastatic colorectal cancer (mCRC), but the efficacy was limited. Anlotinib, an oral anti-angiogenic tyrosine kinase inhibitor, had initially shown promising clinical effects when combined with chemotherapy in the first-line treatment of mCRC. Whether anlotinib could bring clinical benefit in the second line treatment warrants further exploration. The PD-1 antibody might have partial effects when combined with anti-angiogenic agents with or without chemotherapy in first- and third-line treatment for proficient mismatch repair (pMMR)/microsatellite stable (MSS) mCRC. Our study was to explore the rationality of anlotinib plus chemotherapy or further combined with a novel anti-PD-1 IgG1 antibody—penpulimab in the second line treatment of mCRC. Methods: This study was an open label, non-randomized, multi-cohorts, phase II prospective clinical trial that included pts with pMMR/MSS mCRC who were eligible for the second-line systemic treatment. Two cohorts were established as follows: Cohort A consisted of anlotinib(10mg daily, d1-10, q2w) + irinotecan (180mg/m d6, q2w) (n = 23); Cohort B consisted of anlotinib (8mg daily, d1-10, q2w)+irinotecan (180mg/m d6, q2w) + penpulimab (200mg, d6, q2w) (n = 23). The primary endpoint was ORR. Secondary endpoints included progress free survival (PFS), overall survival (OS), duration of response (DoR), disease control rate (DCR) and safety. The ORR was reported at 2024 ASCO, and PFS and OS have been updated in this report. Results: At the cutoff date on August 2024, a total of 23 Pts were enrolled in A cohort, and 23 pts were enrolled B cohort but 21 pts received at least one dose of treatment. The median PFS was 7.87 months (95% CI 5.52-10.22) in A cohort, compared to 7.4 months (95% CI 3.17-11.63) in B cohort, p=0.141. The 6-month, 12-month and 18-month PFS rates in A cohort and B cohort were 69.3% vs 80.7%, 27.5% vs 40.3% and 5.5% vs 22.4%, respectively. The median OS of A cohort was 21.73 months (95% CI 9.43-34.03), compared to 19.17 months (95% CI 11.44-26.90 months) in B cohort, p=0.987. The 12-month and 24-month OS rates in A cohort and B cohort were 64.7% vs 73.1% and 20.2% vs 54.8%, respectively. Safety profile indicated that 65.2% (15/23) and 66.7% (14/21) experienced grade≥3 adverse events in A cohort and B cohort, respectively. Common grade ≥ 3 adverse reactions (≥ 20%) mainly include hypertension (4.35% vs 14.29%), diarrhea (13.04% vs 9.52%), neutrophilopenia (39.13% vs 33.33%), and leukopenia (26.09% vs 9.52%). Conclusions: There was no statistically significant difference in overall efficacy between the two cohorts, but the long-term PFS and OS rates were higher in group B cohort, indicating that immunotherapy may bring long-term survival benefits to certain patients. Clinical trial information: NCT05229003 .