Abstract PS3-02: Induction of Cisplatin/abraxane/pembrolizumab followed by pembrolizumab ± Olaparib Maintenance in triple-negative Metastatic breast cancer patients (COMPLEMENT) – A Randomized, Open-label, Phase II Study

Abstract Background: Triple negative breast cancer (TNBC) is a hard-to-treat disease requiring continuous administration of drugs, necessitating further exploration of optimal maintenance strategy. KEYNOTE-355 has proved that pembrolizumab (pembro) plus chemotherapy (chemo) significantly improved PFS than chemo alone as first-line treatment in PD-L1 positive with a combined positive score (CPS) ≥10. The PARP inhibitor olaparib is established as maintenance therapy for platinum-sensitive populations regardless of BRCA status in the setting of ovarian cancer. Moreover, both preclinical and clinical data supported olaparib and pembro have a synergistic effect, suggesting that the doublet might be a promising maintenance strategy. COMPLEMENT study is a randomized, open-label, phase II study, seeking to investigate if olaparib plus pembro will maintain the clinical benefit achieved after induction therapy with cisplatin and nab-paclitaxel (AP) regimen plus pembro in CPS≥1 mTNBC patients (pts). Methods: Eligible pts with locally advanced, recurrent or metastatic PD-L1 CPS ≥1 TNBC that had not been treated with chemo for the advanced disease received induction therapy of pembro (200 mg day, Q3W) + AP regimen (nab-paclitaxel 125 mg/m2 on day 1, 8 and cisplatin 75 mg/m2 on day 1, Q3W) for 4-6 cycles. Pts who have achieved CR, PR, SD based on the RECIST 1.1 criteria were eligible for maintenance period and were randomized to receive either pembro (200mg Q3W) plus olaparib (300mg po bid) group or pembro mono group until disease progression or withdrawal of consent. Pts were stratified by response status (CR or PR vs SD), genomic tumor status (BRCAm vs BRCAwt) and visceral metastases (yes vs no). The primary end point was PFS. And the key second endpoints were ORR, OS and safety signals. Results: At the May 31, 2024 data cutoff, 52 pts have been enrolled. 20 pts (38%) were PD-L1 CPS ≥10 while 32 pts (62%) were PD-L1 CPS <10. 4 pts (8%) carried germline BRCA 1/2 mutation. 41 pts (78.8%) had TNBC at initial diagnose while 11 pts (21.2%) did not but conversed to TNBC in the recurrent lesions. At the induction stage, the overall response rate was 86.5%, the median depth of response was 60% and the median time to response was 1.5 months. A total of 29 pts (28 PR and 1CR) were randomly assigned to pembro mono group (n=15) or combo group (n=14) for maintenance treatment. 9 pts were not randomized due to disease progression and 14 pts were still at the induction stage. In pts with a follow-up time more than 12 months, the 12-month PFS rate was 72.7% (8/11). Preliminary results showed pts with conversion to TNBC obtained less clinical benefit from this maintenance strategy than pts without conversion (6.6 vs. 12.3 months). Immune-related AEs were reported in 11 (21.2%) pts, of whom 5 (9.6%) pts experienced hypothyroidism, 2 (3.8%) pts experienced pneumonitis, 2 (3.8%) pts experienced hepatitis, 1 (2%) pt experienced adrenal insufficiency and hypophysis, 1 (2%) pt experienced nephritis, and 1 pt (2%) experienced severe skin reaction. Treatment-related AEs were reported in all the pts, while grade ≥3 treatment-related AE occurred in 32 pts (61.5%) including neutrophil count decreased (52%), thrombocytopenia (4%), anemia (13%) and ALT/AST increased (8%). Conclusions: Preliminary data indicated that induction therapy with pembro + AP was a highly potent regimen in the first-line treatment of TNBC with no new safety signal, and pts with conversion to TNBC seemed to benefit less from this regimen. More efficacy and safety data between two groups will be shared in the future. Citation Format: Xichun Hu, Chengcheng Gong, Zhonghua Tao, Biyun Wang, Leiping Wang, Jun Cao, Mingchuan Zhao, Jian Zhang, Jian Huang. Induction of Cisplatin/abraxane/pembrolizumab followed by pembrolizumab ± Olaparib Maintenance in triple-negative Metastatic breast cancer patients (COMPLEMENT) – A Randomized, Open-label, Phase II Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS3-02.