Surufatinib combined with TAS-102 as a late-line therapy in patients with metastatic pancreatic cancer (mPDAC): Updated results of a single-arm, phase II trial.

739 Background: Patients (pts) with mPDAC recurrent after FOLFIRINOX and AG chemotherapies have few treatment options. Previous reports of NCT05481463 showed promising clinical benefits of surufatinib (a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) plus TAS-102 (combination of trifluridine and tipiracil hydrochloride) in recurrent mPDAC pts. Here, we report the updated results. Methods: This is a single-arm, phase II trial (NCT05481463). Eligible pts with histologically confirmed mPDAC, who had progressed after ≥ 2 lines of previous therapies were treated with surufatinib (250mg, qd, po, q4w) and TAS-102 (35 mg/m 2 , bid, po, days 1–5 and 8–12, q4w). The primary endpoint was progression-free survival (PFS). Key secondary endpoint was overall survival (OS). Other secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Results: Up to Sep 18, 2024, 20 pts were enrolled (median age 58 years, male 70.0%, TNM stage IV 100.0%, ECOG PS 1 100.0%, liver metastasis 50.0%, peritoneum metastasis 50.0%). Median baseline CA19-9 level of the 20 pts was 996.7u/ml, with a range from 2u/ml to 16612u/ml. 40.0% of pts had received 3L prior therapies before enrollment and 70.0% with primary site on pancreatic body and tail. All pts had received at least one post-baseline tumor assessment (evaluable), among which ORR was 15.0% (3 PRs), DCR was 30.0% (3 PRs, 3SDs). 35.0% pts had stable or shrinking tumors. Median PFS was 2.35m (95% CI 1.91-3.94). Median OS was 6.44m (95% CI 3.81-NR). In subgroup analysis, significantly longer PFS&OS were observed in pts without liver metastasis (mPFS: 3.42m vs 2.01m, p=0.049; mOS: 9.92m vs 3.70m, p=0.026), or with ≤ 2 metastatic organs (mPFS: 3.94m vs 1.91m, p=0.005; mOS: 10.09m vs 3.81m, p=0.003). Additionally, OS was significantly prolonged in pts with baseline CA19-9 level ≤ 996.7u/ml, in contrast with those with baseline CA19-9 level more than 996.7u/ml (9.92m vs 3.70m, p=0.008). All pts experienced treatment emergent adverse events (TEAEs). Most common (≥ 10%) TEAEs (any grade) were anemia (59.1%), neutropenia (54.6%), leukopenia (50.0%), and lymphopenia (45.5%). Grade ≥ 3 TEAEs included neutropenia (31.8%), lymphopenia (13.6%), and anemia (9.1%). Conclusions: Surufatinib plus TAS-102 showed encouraging survival benefits and promising anti-tumor activity with acceptable toxicity in the late-line treatment of refractory mPDAC, especially in patients without liver metastasis, with ≤ 2 metastatic organs, or with baseline CA19-9 level ≤ 996.7u/ml. The results warrant further investigations in a large cohort. Clinical trial information: NCT05481463 .