Preliminary results of ALTER-PA-001 trial: A multicenter, open-label, randomized, phase II trial of anlotinib and benmelstobart in combination with AG versus AG as first-line treatment for metastatic pancreatic cancer.

719 Background: Metastatic pancreatic cancer (mPC) is one of the most challenging malignancies worldwide. While nab-paclitaxel and gemcitabine (AG) are still current standard first-line therapy with limited anti-tumor effect, new treatment options are needed to be explored. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor, which mainly block VEGFR, PDGFR, FGFR and c-kit pathways. Benmelstobart is a humanized PD-L1 monoclonal antibody. Both of them had been proved to be effective and safe as treatment regimen in several solid tumors, such as SCLC, endometrial carcinoma, renal cell carcinoma. This randomized phase II trial aims to evaluate the efficacy and safety of anlotinib plus benmelstobart and AG versus AG as first-line treatment for mPC patients. Methods: ALTER-PA-001 is a multicenter, open-label, randomized, phase 2 trial. Eligible treatment naïve mPC patients are aged 18-75, ECOG 0-1, with histologically or cytologically confirmed PC. A total of 104 patients will be randomly assigned in a 2:1 ratio, with stratification factor of liver metastases (yes or no), to receive anlotinib (8 mg orally, QD, d1–14), benmelstobart (1200 mg IV, d1) and AG regimen (nab-paclitaxel, 125 mg/m² IV, d1, d8 and gemcitabine, 1000 mg/m² IV, d1, d8) every 21 days (Anlotinib group) or AG regimen (AG group). Patients achieving CR, PR, or SD after 8 cycles of treatment will enter a non- nab-paclitaxel maintenance treatment. The primary endpoint is ORR, while secondary endpoints include PFS, DCR, DoR, OS and safety. Results: As data cutoff date of August 25, 2025, a total of 41 mPC patients enrolled, of which 29 patients in Anlotinib group and 14 in AG group. The median age of were 63 (range 47-74). 61.0% (25/41) were male and 82.9% (34/41) were ECOG PS 1. The ratio of primary tumor site of pancreatic head, body and tail were 46.3%, 26.8% and 26.8%, respectively. 6 patients (14.6%, 6/41) had primary tumor resection. With a median follow-up of 2.7 months (range 0.1-9.5), 32 patients were tumor assessment available. Among tumor assessment available patients in Anlotinib Group (N=20), 8 had achieved PR, and 10 had SD, and 2 had PD. While in AG group (N=12), 2 had achieved PR, and 9 had SD, and 1 had PD. The ORR was 40.0% (8/20) and 16.7% (2/12) in each group. The DCR were 90.0% (18/20) and 91.7% (11/12), respectively. The incidence of TEAE were 88.9% and 92.9% in Anlotinib and AG group, respectively. The most common TEAE were white blood cell decreased (51.9% vs. 50.0%), anemia (44.4% vs. 42.9%) and neutrophil count decreased (40.7% vs. 42.9%). Conclusions: The preliminary results had demonstrated a potent efficacy of anlotnib plus benmelstobart and AG as first-line treatment for mPC patients, with a manageable safety profile. Clinical trial information: NCT06621095 .