Toripalimab combined with nab-paclitaxel/gemcitabine as first-line treatment for advanced pancreatic adenocarcinoma: Updated results of a phase Ib/II clinical study.

e16244 Background: Much controversy remains regarding the immune-checkpoint-inhibitor plus Nab-paclitaxel/gemcitabine (AG) as the treatment in advanced pancreatic ductal adenocarcinoma (aPDAC). We assess safety and efficacy of toripalimab plus AG in aPDAC, this was the updated results of the study. Methods: This was a phase Ib/II clinical study of toripalimab plus AG as first-line treatment for aPDAC. Toripalimab (240mg, Q3W), combined with AG (nab-paclitaxel 125 mg/m2, d1, d8 plus gemcitabine 1000 mg/m2, d1, d8) were administrated until the disease progresses/unacceptable toxicity or receiving toripalimab maintenance treatment. The primary endpoints were safety and OS; the secondary endpoints were ORR, DCR and PFS. Predictive biomarkers including gene mutations based on next-generation sequencing and PD-L1 expression were assessed. Results: Until January 2022, 55 chemotherapy-naïve aPDAC evaluable patients (beyond 90% patients with metastatic lesions) to safety and response, ECOG PS≤2 were enrolled. The ORR was 29.1%, the DCR was 90.9%, including 15 patients with PR and 1 patient with CR, 34 patients with SD respectively. 33 patients were alive and 16 patients were still ongoing study. Median PFS was 5.0 months (95% CI: 4.033-5.967), the 6-month PFS rate was 56.4%; median OS was 10.0 months (95% CI: 6.321-13.679), the 1-year OS rate was 69.1%. 2 cases of pseudoprogression were observed. The most frequent treatment related adverse events (TRAE) were anemia (90.1%, G3/4: 9.1%), hypoproteinemia (73%, G3/4: 5.5%), AST elevation (61.0%, G3/4: 3.6%), ALT elevation (60%, G3/4: 5.5%), hypothyroidism (51%, G3/4: 0%), leukocytopenia (45.4%, G3/4: 5.5%), neutropenia (44%, G3/4: 9.1%), nausea (44%, G3/4: 3.6%), rash (38.1%, G3/4: 0%). And 23 patients (41.8%) experienced grade 3/4 TRAE. In the biomarker analysis, all 55 patients were MMR-proficient status; 37 patients were evaluated for PD-L1 expression, PD-L1 positive cases (PD-L1 TPS > 1% and/or CPS > 2, n = 12, 6 patients achieved PR) compared with PD-L1 negative cases (n = 25) presented higher ORR (50% vs 16%). 44 patients were investigated for NGS in 55 evaluable patients, KRAS mutation (86.4%) was the most frequently mutated genes (KRAS G12D = 20 patients, KRAS G12V = 13 patients, KRAS G12R = 4 patients, KRAS G12C = 1 patients), and germline BRCA2 mutation was observed in one patient. The correlation between gene mutation and efficacy and prognosis is under analyzed. Conclusions: The updated results of this phase Ib/II study has met our preset primary endpoint with 69.1% in 1-year OS rate, provided promising evidence that toripalimab in combination with AG has a manageable safety profile and expected antitumor activity. The correlation between biomarkers with clinical efficacy are under investigation. The results supported ongoing combined treatment in aPDAC patients. Clinical trial information: ChiCTR2000032293.