Abstract 745P
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
∗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.
Resources from the same session
621P - Phase II trial of encorafenib and binimetinib (E+B) in patients (pts) with BRAF-altered advanced solid tumors: Results of E+B cohort in the BELIEVE trial (NCCH1901)
Presenter: Yoshitaka Honma
Session: Poster session 01
622P - Safety and efficacy of ifebemtinib (IN10018) combined with D-1553 in solid tumors with KRAS G12C mutation: Results from a phase Ib/II study
Presenter: Zhengbo Song
Session: Poster session 01
624P - Belvarafenib in patients (pts) with BRAF class II or III alteration-positive tumours: TAPISTRY study
Presenter: Rafal Dziadziuszko
Session: Poster session 01
625P - Initial results from the phase I, first-in-human study of the covalent, PI3Kα inhibitor TOS-358 in patients with solid tumors, expressing PI3Kα mutations or amplifications
Presenter: Marwan Fakih
Session: Poster session 01
626P - Roginolisib (IOA-244), a first oral allosteric modulator of phosphoinositide 3-kinase inhibitor delta (PI3Kδ) in patients with metastatic uveal melanoma
Presenter: Anna Di Giacomo
Session: Poster session 01
627P - Long-term efficacy and safety of larotrectinib in non-primary central nervous system (CNS) TRK fusion cancer
Presenter: Alexander Drilon
Session: Poster session 01
628P - Efficacy and safety of larotrectinib as first-line treatment for patients (pts) with TRK fusion cancer: An updated analysis
Presenter: David Hong
Session: Poster session 01
629P - Phase I study of pamiparib and cabozantinib in patients with metastatic solid tumors harboring homologous recombination deficiency (HRD)
Presenter: Siqing Fu
Session: Poster session 01