Study designs and outcomes of key clinical trials of immunotherapy in 1L a/rEC.
| Trial | Phase | Population | N pts | Treatment Arms | R | Primary endpoints | mFU | Outcomes |
|---|---|---|---|---|---|---|---|---|
| DUO-E NCT04269200 [24] | III | 1L a/r EC≥ 12 m after platinumcarcinosarcoma included | 718 | Durvalumab (D), Durvalumab + Olaparib (D+O) vs. Placebo (PBO) + CXT | 1:1:1 | PFS ITT [D vs. PBO], PFS ITT [D+O vs. PBO] |
| PFS ITT: D 10.2 m vs. PBO 9.6 m; HR 0.71; p = 0.003; D + O 15.1 m vs. PBO 9.6 m; HR 0.55; p < 0.0001*OS ITT: D NR vs. PBO 25.9 m; HR 0.77; p = 0.120; D + O NR vs. PBO 25.9 m; HR 0.59; p = 0.003PFS dMMR: D vs. PBO HR 0.42; D + O vs. PBO HR 0.41PFS MMRp: D vs. PBO HR 0.77; D + O vs. PBO HR 0.57PFS PD-L1+: D vs. PBO HR 0.63; D + O vs. PBO 0.42 |
| MITO END 3 NCT03503786 [27] | II | 1L a/r ECcarcinosarcoma excluded | 125 | Avelumab (Av) vs. PBO + CXT | 1:1 | PFS ITT | 23 m | PFS ITT: Av 9.9 vs. 9.6 m; HR 0.7812-month PFS dMMR: 60% vs. 35% (p = 0.015)24-month OS dMMR: 76% vs. 55% (p = 0.029) |
| RUBY part 1 NCT04853576 [28] | III | 1L a/r EC≥ 6 m after platinumclear cell, carcinosarcoma, serous, mixed, IIIC2-IVA included | 494 | Dostarlimab (Do) vs. Placebo (PBO) + CTX | 1:1 | PFS dMMR-, PFS ITT and OS ITT | 24 m | PFS dMMR: Do 61.4% vs. PBO 15.7%; HR 0.28; p < 0.001 PFS ITT: Do 36.1% vs. PBO 18.1%; HR 0.64 (0.51–0.80); p < 0.001 OS ITT: Do 71.3% vs. PBO 56%; HR 64 (0.46–0.87); p = 0.0021PFS MMRp: Do 28.4% vs. PBO 18.8%; HR 0.76OS dMMR: Do 83.3% vs. PBO 58.7; HR 0.30OS MMRp: Do 67.7% vs. PBO 55.1%; HR 0.79 |
| NRG-GY018 NCT03914612 [31, 32] | III | 1L a/r EC≥ 12 m after platinumcarcinosarcoma excluded | 816 | Pembrolizumab (P) vs. Placebo (PBO) + CTX | 1:1 | PFS dMMR, PFS MMRp | 12 m | dMMR PFS: P NR vs. PBO 7.6 m; HR 0.30; p < 0.001MMRp PFS: P 13.1 m vs. PBO 8.7 m; HR 0.54; p < 0.001dMMR OS: HR 0.55MMRp OS: HR 0.79 |
| RUBY part 2 NCT03981796 [33] | III | 1L a/r EC≥ 6 m after platinumclear cell, carcinosarcoma, serous, mixed, IIIC2-IVA included | 291 | Dostarlimab (Do) + Niraparib (N) vs. Placebo (PBO) + CTX | 2:1 | PFS, ITT | NA | PFS ITT: Do + Nira 14.5 vs. 8.3; HR 0.60PFS dMMR: HR 0.45PFS MMRp: HR 0.63 |
| AtTEnd NCT03603184 [34] | III | 1L a/rEC and ≥ 6 m after platinumcarcinosarcoma included | 551 | Atezolizumab (A) vs. Placebo (PBO) + CXT | 2:1 | PFS dMMR > PFS ITT > OS ITT | 28.3 m | PFS dMMR: A NR vs. PBO 6.9 m; HR 0.36; p = 0.0005PFS ITT: A 10.1 m vs. PBO 8.9 m; HR 0.74; p = 0.022OS ITT: A 38·7 m vs. PBO 30.2 m; HR 0.82; log-rank p = 0.048PFS MMRp: HR 0.92OS MMRp: HR 1.00 |
| LEAP-001 NCT03884101 [38] | III | 1L a/r EC≥ 6 m after platinum | 842 | Pembrolizumab (P) + Lenvatinib (L) vs. CTX | 1:1 | PFS ITT, OS ITT | 38.4 m | PFS MMRp: P + L 9.6 vs. CTX 10.2 m; HR 0.99 PFS ITT: P + L 12.5 vs. CTX 10.2 m; HR 0.91OS MMRp: P + L 30.9 vs. 29.4 m HR 1.02 OS ITT: 37.7 vs. 32.1 m HR 0.93 |
1L: first line; a/rEC: advanced and recurrent endometrial cancer; CTX: chemotherapy (platinum plus paclitaxel); D: durvalumab; dMMR: defective mismatch repair; HR: hazard ratio; ITT: intention-to-treat; mFU: median follow-up; MMRp: proficient mismatch repair; NA: not applicable; NR: not reached; OS: overall survival; PD-L1: programmed death-ligand 1; PFS: progression-free survival; R: randomization. * The PFS comparison between Durvalumab alone and placebo was not formally tested for statistical significance according to the predefined hierarchical testing strategy of the DUO-E trial.