Benmelstobart plus carboplatin/paclitaxel with or without anlotinib, followed by maintenance benmelstobart with or without anlotinib, as first-line treatment for advanced or recurrent endometrial cancer: A randomized, open-label, phase II trial.

5508 Background: Immunotherapy combined with chemotherapy has demonstrated efficacy in treating endometrial cancer (EC), with greater benefit in mismatch repair (MMR)–deficient (dMMR) tumors compared to MMR-proficient (pMMR) disease. Adding an anti-angiogenic inhibitor could potentially enhance treatment outcomes, particularly in patients with pMMR tumors. Benmelstobart (BMSB, TQB2450) is a humanized monoclonal antibody against PD-L1 and Anlotinib (ALTN) is an anti-angiogenic oral multi-target tyrosine kinase inhibitor. Here, we report the results of a randomized, open-label, phase 2 trial comparing BMSB plus carboplatin/paclitaxel ± ALTN followed by maintenance BMSB ± ALTN as first-line treatment for advanced or recurrent EC patients. Methods: Eligible patients with primary advanced stage III/IV or recurrent EC, who had not received first-line systemic anticancer therapy, were randomized in a 1:1 ratio to receive either BMSB 1200mg, Carboplatin (CBP, AUC=5 mg/ml.min) and Paclitaxel (PTX, 175mg/m 2 ) every 3 weeks for 6-8 cycles plus ALTN 8mg orally once daily (2-week on/1-week off), followed by maintenance BMSB 1200mg every 3 weeks and ALTN 10mg once daily (2-week on/1-week off) (BMSB + ALTN arm); or BMSB 1200mg, CBP (AUC=5 mg/ml.min) and PTX 175mg/m 2 every 3 weeks for 6-8 cycles followed by maintenance BMSB 1200mg every 3 weeks (BMSB arm). Stratification factors included MMR status (dMMR or pMMR). The primary endpoint was objective response rate (ORR) as assessed by investigator according to RECIST 1.1. Results: As of November 1, 2024, a total of 71 patients were enrolled: 38 in the BMSB + ALTN arm, and 33 in the BMSB arm. The median duration of follow-up was 16.2 mo vs. 14.2 mo in the two arms respectively. The ORR was 86.1% (95% CI: 70.5-95.3) in the BMSB + ALTN arm and 80.6% (95% CI: 62.5-92.5) in the BMSB arm. A significant PFS benefit was observed in the BMSB + ALTN arm (HR 0.38 [95% CI 0.18-0.81]; median not reached (NR) vs. 8.41 mo) compared to the BMSB arm. The median overall survival (OS) was not reached in either arm (HR=0.29 [95% CI: 0.07-1.16]). PFS benefit was also observed in subgroups with pMMR tumors (HR 0.35 [95% CI 0.15-0.79]). The incidence of Grade ≥3 TEAEs was similar between the two arms (81.58% vs 75.76%). The most frequent Grade ≥3 TEAEs(≥20%) were decreased white blood cell count (52.63% vs 60.61%), thrombocytopenia (28.9% vs 27.2%) and anemia (26.3% vs 27.7%). Conclusions: Benmelstobart combined with carboplatin/paclitaxel and anlotinib, followed by maintenance benmelstobart and anlotinib, demonstrated clinically meaningful ORR and PFS benefits in patients with previously untreated advanced or recurrent EC. The regimen was particularly helpful in improving outcomes for patients with pMMR tumors, potentially providing a new treatment option. Clinical trial information: NCT05481645 .