1065 Background: SG was evaluated in the phase 3 ASCENT-07 study (NCT05840211) of pts with HR+/HER2−, locally advanced unresectable or mBC who had received prior endocrine therapy (ET) and were eligible for first chemotherapy; the primary end point (PFS by blinded independent central review BICR vs chemotherapy treatment of physician’s choice TPC) was not met (HR 0.85; 95% CI, 0.69-1.05; P = .130). We report exploratory outcomes in pts with HER2 IHC0 expression status. Methods: Pts were randomized 2:1 to receive SG 10 mg/kg IV or TPC (capecitabine, nab-paclitaxel, or paclitaxel). Descriptive analyses of pts with HER2 IHC0 were performed for the primary end point of PFS by BICR, secondary end points of PFS by investigator (INV), overall survival (OS), objective response rate (ORR) and duration of response (DOR) by BICR, and safety. HER2 status was tested locally. Results: Of 690 pts enrolled, 292 (42%) had HER2 IHC0 (SG: 192; TPC: 100). Baseline demographics and pt characteristics were similar to the overall population. Median age was 58 yrs; 176 (92%) and 91 (91%) pts in SG and TPC groups, respectively, received prior ET + CDK4/6i in the metastatic setting; 88% and 86% had visceral disease. At 15.4-mo median f/u, SG showed numerical improvement in PFS vs TPC by BICR (HR 0.75; 95% CI 0.55-1.02; nominal P = .0601) and by INV (HR 0.66; 95% CI 0.50-0.86; nominal P = .0024). Although OS data were not mature (maturity rate for IHC0 subgroup, 28%), an early improvement trend favoring SG was observed. ORR by BICR was similar for SG and TPC, and median DOR by BICR was longer for SG vs TPC. Despite a higher proportion of pts experiencing grade ≥ 3 treatment-emergent adverse events (TEAEs) with SG vs TPC, the rate of treatment discontinuation was lower with SG (Table). The most common grade ≥ 3 TEAEs were neutropenia (SG: 54%; TPC: 21%), leukopenia (12%; 7%), and anemia (11%; 5%). Safety profile was consistent with overall population and prior reports. Conclusions: In this exploratory analysis from ASCENT-07, numerical trends of improved efficacy vs TPC and the overall population as well as a manageable safety profile support further investigation into the potential benefit of SG in patients with HR+/HER2− mBC and HER2 IHC0 status who are candidates for first chemotherapy. Clinical trial information: NCT05840211 . SG (n = 192) TPC (n = 100) Median PFS by BICR (95% CI), mo 9.2 (8.2-10.4) 8.1 (6.3-10.4) HR (95% CI) 0.75 (0.55-1.02); P = .0601 a Median PFS by INV (95% CI), mo 8.5 (8.2-10.4) 6.1 (4.5-8.1) HR (95% CI) 0.66 (0.50-0.86); P = .0024 a Median OS (95% CI), mo Not reached (NR-NR) 20.2 (19.5-NR) HR (95% CI) 0.68 (0.44-1.05); P = .0820 a ORR by BICR (95% CI), % 41 (34-48) 40 (30-50) Median DOR by BICR (95% CI), mo n = 78 10.8 (6.4-12.6) n = 40 8.3 (5.5-11.2) TEAEs, n (%)Any gradeGrade ≥ 3Led to dose reductionLed to treatment discontinuation n = 190 189 (99)139 (73)83 (44)4 (2) n = 100 97 (97)46 (46)35 (35)7 (7) a Nominal P value; unstratified log rank.
Park et al. (Wed,) studied this question.