A Phase Ii Study Of Pembrolizumab (P) In Combination With Doxorubicin (D) In Advanced Endometrial Cancer (Aec): Topic Trial/Vhio10001

No standard second-line treatment is available for AEC after failure to platinum-based chemotherapy in Europe. P conferred a 57% objective response rate (ORR) in patients (pts) with mismatch repair-deficient (MMRd) AEC. However, MMR-proficient (MMRp) AEC pts experience less benefit from immunotherapy. Our hypothesis was that P with an inducer of immunogenic cell death such as D could improve clinical responses in all AEC subtypes. This was an investigator-initiated, single-arm, multicentre, phase II study in pts with AEC who have received one prior line of platinum-based chemotherapy (NCT03276013). Pts received D 60 mg/m2 i.v. every 3 weeks for up 9 cycles + P 200 mg up 36 cycles, or until progression or toxicity. Primary endpoint was progression-free survival (PFS) rate at 6 months (m). Secondary endpoints included ORR, duration of response (DOR), PFS, overall survival (OS) and safety. A total of 48 pts were enrolled. Median age was 66 years (range, 37-80). Most common EC histological types: endometrioid (64.6%), serous (20.8%), carcinosarcoma (8.3%), mixed carcinoma (4.2%) and others (2.1%). Median follow-up was 19.1 m with a median PFS of 6.2 m (95%CI, 4.8 – 8.7). The 6-m PFS was 53% (95%CI, 40.4% – 69.5%), which was a statistically significant improvement compared to the pre-defined 24% based on historical data (p< 0.001). The 6-m PFS rate was higher for patients with endometroid vs patients with non-endometroid histological subtype (63% vs 35%). The ORR was 31.3% (12.5% complete responses). Median OS and DOR were 16.3 (95%CI, 11.8 – NR) and 8.2 m (95%CI, 6.2 – NR), respectively. Serious treatment-related adverse events (TRAE) occurred in 7 (15%) patients, and one treatment-related death due to intracranial haemorrhage was reported. The most common grade ≥3 TRAE were neutropenia (25%) and lymphocyte count decreased (8.3%). The combination of pembrolizumab and doxorubicin showed promising antitumor activity with a manageable safety profile in women with AEC after failure to platinum therapy. Translational analyses are ongoing to correlate biomarkers with outcomes.