An Open-Label, Placebo-Controlled, Randomized Phase II Trial of Camrelizumab Combined with or Without Apatinib or Capecitabine in the Treatment of Previously Treated Advanced Pancreatic Cancer.

e16324 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the few cancer types that have essentially no clinical benefit from immune checkpoint inhibitors therapy, combined immunotherapy is expected to solve this dilemma. We conducted a randomized open-label, placebo-controlled phase II trial evaluating the efficacy of camrelizumab combined with apatinib or capecitabine in the treatment of patients with previously treated metastatic PDAC (ChiCTR1900024095). Methods: Eligible patients (n = 30) were randomized 1:1:1 to receive camrelizumab (200 mg q2w) combined with apatinib (250mg qd, d1-28, q4w) or capecitabine (1000 mg/m2, bid d1-14, q3w), or placebo plus capecitabine (1000 mg/m2, bid d1-14, q3w) until disease progression or unacceptable toxicity. Tumor response was assessed every 8 weeks according to RECISTv1.1. Primary endpoints were investigator-assessed 6-month overall survival (OS) rate. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety. Data cutoff date for the prespecified interim OS and final PFS analysis was Oct 30, 2022. Results: In the primary endpoint analysis, camrelizumab combined treatment showed improved 6-month OS rates, whether in the camrelizumab-apatinib arm (83.3% versus 33.3%, p = 0.1189) or in the camrelizumab-capecitabine arm (100% versus 33.3%, p = 0.0098), compared placebo-capecitabine, respectively. Median PFS was 5.4 months, HR 0.58, [95% confidence interval (CI), 0.21–1.59] in the camrelizumab-apatinib arm , 3.1 months HR 0.98, [95%CI, 0.35–2.77] in the camrelizumab-capecitabine arm , and 2.6 months in the placebo-capecitabine, respectively. The ORR and DCR were 0% and 66.7% in the camrelizumab-apatinib arm, 40% and 50% in the camrelizumab-capecitabine arm, 0% and 44.4% in the placebo-capecitabine, respectively. PR was observed in two patients receiving camrelizumab-capecitabine treatment. The median DoR were 5.3 months in the camrelizumab-apatinib arm, 4.3 months in the camrelizumab-capecitabine arm, and 2.1 months in the placebo-capecitabine arm. Treatment-related adverse event rates were slightly increased in camrelizumab combined arms. Incidences of grade ≥3 treatment-related adverse events were comparable between the three groups (20%、 10% vs 0%), with reactive cutaneous capillary endothelial proliferation (10%) as the most common one in Camrelizumab combinations. Conclusions: Camrelizumab combined treatment showed improved 6-month OS vs conventional capecitabine monotherapy, with a manageable safety profile. These analyses revealed combined immunotherapy could be used as a new option for posterior line treatment in previously treated metastatic PDAC. Clinical trial information: ChiCTR1900024095.