Background: Treatment options in recurrent endometrial carcinoma (EC) are limited. Endometrioid EC shows alterations in PTEN, a possible biomarker of response to PARP inhibitors (PARPi). Similarly, homologous recombination deficiency (HRd), a biomarker of response to PARPi in ovarian cancer, is associated with serous EC harbouring TP53 mutations. Preclinical EC models have shown synergy between combining a PARPi and immune checkpoint inhibitor (ICI). Methods: A pilot multi-centre, non-randomized, phase II trial enrolled patients (pts) with recurrent serous or endometrioid EC in two consecutive cohorts (NCT03016338). In the first cohort (C1) pts received niraparib 200 or 300 mg qd, based on baseline body weight and platelet count, in 4 week (w) cycles. In the second cohort (C2) niraparib was given with dostarlimab 500 mg q 3 w for 4 cycles, followed by 1000 mg q 6 w thereafter. There was no limit on prior lines of therapy. Prior ICI was not allowed in C2. Primary endpoint was clinical benefit rate (CBR; complete, partial response or stable disease ≥16w). Secondary endpoints included toxicity assessment and ORR. CT scans were performed q 8 w. Potential biomarkers were assessed in archival tissue by IHC (PTEN, p53, MMR, PDL-1 [threshold 1%]) and a NGS panel (including TP53, PTEN, POLE and other HRd genes). Tumour mutational burden-high (TMBh) was defined as top 20% mutation load. Results: In C1, 25 pts were enrolled (23 evaluable for response). Median age was 69 years old, 64% had serous EC, 72% were platinum resistant (PlatR) and median prior therapies was 2 (range 1-4). Median number of cycles was 3. The CBR was 20% (95% CI: 9-39) and median clinical benefit (CB) duration was 5.3 (1.8-7.2) months. The ORR was 1/23 (4%; 0-20). Related grade (g) ≥3 AEs ≥10% were anemia (24%), fatigue (16%) and thrombocytopenia (16%). In C2, 22 pts were enrolled (all evaluable) and two continue on-treatment. Median age was 64 years old, 46% had serous EC, 68% were PlatR and median prior therapies was 2 (1-6). Three pts had MMR deficient (MMRd) tumors (14%) and one pt a POLE mutation (5%). Median number of cycles was 3. The CBR was 31.8% (16-53) and median CB duration was 6.8 months (3.7-9.5). The ORR was 3/22 (14%; 3-35), out of the three responders one had MMRd and one a POLE mutation. Related g≥3 AEs ≥10% were anemia (27%) and neutropenia (14%). No significant correlation was detected between CB and IHC markers (PTEN, p53, MMR, PDL-1), or NGS (PTEN, TP53, HRd TMBh) in C1 and C2. Conclusions: Niraparib as single agent for treatment in a PlatR enriched recurrent EC population showed modest activity with clinical benefit rate at 16w of 20%. The combination of niraparib and dostarlimab showed a clinical benefit rate at 16w of 31.8% in a predominantly PlatR recurrent EC. PTEN loss by IHC or NGS, and alterations in HRd genes did not correlate with clinical benefit. Clinical trial information: NCT03016338