TOPACIO/Keynote-162: Niraparib + pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC), a phase 2 trial.

Abstract

1011 Background: Chemotherapy is a standard of care for TNBC despite its suboptimal efficacy. ≈15–20% of TNBC have BRCA1/2 mutations (mut); ≈75% of BRCA1 mut BCs are TN. Single agent poly(ADP-ribose) polymerase (PARP) inhibitors have clinical activity in pts with BRCA1/2 mutations (BRCAmut) BC and provide median PFS of 6 mos in pts with BRCAmut TNBC vs 3.5 mos for chemotherapy. Single-agent pembrolizumab (pembro), a programmed death 1(PD–1) inhibitor, has shown objective response rates (ORR) of 5–18% in previously treated TNBC. TOPACIO (NCT02657889) is a fully enrolled study evaluating the safety and efficacy of combination treatment with selective PARP1/2 inhibitor niraparib + pembro in pts with met TNBC. Methods: Pts received niraparib 200 mg orally once daily + pembro 200 mg IV on day 1 of each 21-day cycle. Primary efficacy endpoint was ORR and secondary endpoints included disease control rate (DCR = CR+PR+SD [stable disease]). Results: As of Jan 2018, 12 of 54 enrolled TNBC pts (22%) had deleterious BRCAmut; 9 (17%) not tested/indeterminate results. Median age was 54 yrs, with median of 1 prior line of therapy in the met setting (range 0–3); 22 (41%) had received prior platinum in the met setting; 39 (72%) had received prior (neo)adjuvant therapy. Forty-five pts were evaluable, with ≥1 on-study scan. To date, ORR is 29% and DCR is 49%, including 3 CR (7%), 10 PR (22%), 9 SD (20%), and 23 progressive disease (PD) (51%). Ten of 13 responders have ongoing responses; 13 pts have received > 6 mos of treatment (6 BRCAmut, 5 BRCAwt, 2 BRCAunk); 11 pts remain on treatment. The 12 BRCAmut pts were 1 CR, 7 PR, 1 SD and 3 PD. Median PFS in BRCAmut group is 8.1 mos (95% CI 0.2–NE). ORR (any BRCA status) was 33% in PD-L1-pos (combined proportion score ≥1%) vs 15% in PD-L1-neg pts. Treatment-related grade ≥3 AEs occurred in 27 pts (50%); most common were thrombocytopenia (13%) & anemia (11%). Follow-up is ongoing. Conclusions: Preliminary activity is encouraging with durable responses observed irrespective of BRCA1/2 or PD-L1 status or prior platinum exposure with the highest ORR in BRCAmut pts. No new safety signals were identified with the combination. Clinical trial information: NCT02657889. ORR DCR TNBC overall, n = 45 29% 49% TNBC BRCAmut, n = 12 67% 75%