A phase Ib, open-label, multi-cohort study of metronomic capecitabine plus camrelizumab for treatment of refractory solid tumor: McCrest trial.

Abstract

e16079 Background: The efficacy of immune checkpoint inhibitors (ICIs) monotherapy for refractory solid tumor is relatively poor. Combination therapy is an effective strategy to improve its efficacy. Metronomic chemotherapy that can modulate tumor immunomicroenvironment is a potential partner for ICIs, which is also well-tolerated and low-cost. Methods: This was a phase Ib, open-label, single-center, multi-cohort study designed to evaluate the safety and efficacy of camrelizumab combined with metronomic capecitabine for refractory solid tumors. Patients who were disease progression after standard treatment could be enrolled. PD-L1 status was not compulsory. Capecitabine was administrated orally at 500mg bid every day, with camrelizumab at 200mg IV on Day 1 of a 14-day cycle. Primary endpoint was adverse events (AEs). Secondary endpoints including progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR). The exploratory endpoint was also set to identify the potential molecular alterations during treatment by liquid biopsy analysis. Results: As of December 12, 2021, 19 patients were enrolled including gastric cancer (8), esophageal cancer (6), pancreatic cancer (2), cholangiocarcinoma (2) and duodenal cancer (1). Ten patients had 2 or more prior lines of therapy. The common treatment-related AEs including reactive cutaneous capillary endothelial proliferation (10/19), fatigue (9/19), leukemia (5/19), anemia (5/19), hyponatremia (4/10) and blood bilirubin increased (4/19). Grade 3 AEs including fatigue (2/19) and bronchitis (1/19), and no grade 4 AEs was observed. Three patients suffered severe AEs, including bowel perforation (1), bowel obstruction (1) and bleeding (1), which were all treatment unrelated. There were 4 patients still under treatment, and median number of treatment cycle was 4 (1-16 cycles). The median PFS and OS was 2.1 months (95%CI 1.9-2.3 months) and 5.1 months (95%CI 1.6-8.5 months) respectively. Partial response was observed in 1 esophageal cancer patient with PD-L1 TPS < 1. For 12 patients with assessable lesions, the DCR was 41.6% (5/12). Peripheral blood samples were collected during treatment, and molecular alterations after administration of metronomic capecitabine and camrelizumab were under analysis. Conclusions: The combination of metronomic capecitabine plus camrelizumab was well tolerated in patients with refractory solid tumors. Its efficacy should be assessed in further study. Clinical trial information: NCT04508686, NCT04510818, NCT04932187.