745P - Biomarker-driven targeted therapy in platinum-resistant ovarian cancer (BRIGHT): An open-label, multicenter, umbrella trial

Background

Platinum-resistant, recurrent ovarian cancer (PROC) has poor prognosis with limited treatment options. The BRIGHT trial (NCT05044871) aimed to evaluate the efficacy and safety of biomarker-driven targeted combinatorial therapies of pamiparib (Pami, a PARP inhibitor), tislelizumab (TIS, a PD-1 inhibitor), bevacizumab (BEV), and nab-paclitaxel (nab-PTX) in pts with PROC. Here, we report the primary analysis results.

Methods

Pts with PROC were assigned based on their BRCA mutation status and CD8⁺ TILs count to receive Pami + BEV (Arm 1, BRCAm; N=40), TIS + BEV + nab-PTX (Arm 2, BRCAwt and CD8⁺ TILs ≥3; part 1 [N=50], part 2 [N=20]), or BEV + nab-PTX (Arm 3, BRCAwt and CD8⁺ TILs <3; N=50). The Bayesian method was used to update ORR observed in part 1 of Arm 2. Primary endpoints were ORRs of each arm, and ORR in part 1 of Arm 2.

Results

105 pts were enrolled and assigned to Arm 1 (N=29), Arm 2 (N=70), and Arm 3 (N=6). Most pts with BRCAwt tumors (92.1%; 70/76) had positive CD8⁺ TILs (≥3). ORRs in each arm were 23.1%, 41.5%, and 60.0%, respectively (Table); ORR in part 1 of Arm 2 was 46.0% (95% CI 31.8-60.7). Pts with higher CD8⁺ TILs tended to have higher ORR in Arm 2 (CD8⁺ TILs ≥12, 50.0% [24/48]; CD8⁺ TILs ≥3 - 1 mo - ≤3 mo 9 (31.0) 20 (28.6) 2 (33.3) >3mo - ≤6 mo 11 (37.9) 32 (45.7) 2 (33.3) Efficacy ^# N=26 N=65 N=5 ORR, % (95% CI) 23.1 (9.0, 43.7) 41.5 (29.4, 54.4) 60.0 (14.7, 94.7) DCR, % (95% CI) 73.1 (52.2, 88.4) 76.9 (64.8, 86.5) 100.0 (47.8, 100.0) Median PFS, mo (95% CI) 4.1 (1.4, NA) 7.3 (4.8, 8.2) 11.7 (3.4, NA) Median DoR, mo (95% CI) NA (2.8, NA) 5.9 (4.3, 9.1) 8.8 (7.3, NA)

∗Based on safety analysis set.

#based on efficacy analysis set.

§from last platinum to subsequent disease progression.

Conclusions

These findings highlight the potential clinical benefits of biomarker-driven targeted therapies in pts with PROC. The majority of pts in this study had BRCAwt tumors with positive CD8⁺ TILs (≥3), and PD-1 inhibitor-based combinatorial regimen (TIS + BEV + nab-PTX) resulted in notable ORR and PFS in this patient population.

Clinical trial identification

NCT05044871.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

BeiGene Ltd.

Disclosure

All authors have declared no conflicts of interest.