Prevention of sacituzumab govitecan (SG)-related neutropenia and diarrhea in patients (pts) with triple-negative or HR+/HER2- advanced breast cancer (ABC; PRIMED): A phase 2 trial.

1101 Background: SG is a Trop-2 directed antibody-drug conjugate approved for pts with advanced, pretreated, triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer. The most common SG-related adverse events (AEs) are neutropenia and diarrhea which can lead to treatment modifications. Granulocyte colony-stimulating factor (G-CSF) and loperamide (L) are frequently used for managing these AEs. PRIMED is assessing if primary prophylaxis with G-CSF and L can improve the tolerability of SG. Methods: PRIMED (NCT05520723) is an open-label, single-arm, phase II trial. Pts had received between 1-2 previous chemotherapy regimens for ABC, including a taxane in any setting, unless contraindicated. HR+/HER2- pts had to be endocrine-resistant. Pts received SG (10 mg/kg IV, d 1 and 8, every 21 d) until disease progression (PD) or unacceptable toxicity. G-CSF (0.5 MU/kg/day SC, d 3, 4, 10, and 11) and L (2 mg orally, twice a day or 4 mg QD, d 2, 3, 4, 9, 10, and 11) were given during the first two cycles. The primary endpoints were incidence of ≥ grade (G) 3 neutropenia (H0: ≥40%; H1: ≤22%) or ≥ G 2 diarrhea (H0: ≥25%; H1: ≤10%) after two cycles. Results: A total of 50 pts were enrolled between February 2023 and September 2023 (TNBC, n = 32 [64%]). At data cut-off on October 18, 2023 (median follow-up, 4.3 months), 31 pts remained on treatment. The main reason for treatment discontinuation was PD, which was reported for 16 pts. After the first two cycles, incidence of any G neutropenia and diarrhea were 28% and 34%, respectively. Eight pts (16%) had ≥ G 3 neutropenia, meeting this primary endpoint (p=0.0002). Eight pts (16%) had ≥ G 2 diarrhea (4% G 3), showing numerical benefit of prophylactic L (p=0.084). No pts developed febrile neutropenia. The overall rate of AEs associated with dose reductions and treatment interruptions was 18% and 44%, respectively. No treatment discontinuations due to AEs were reported. Conclusions: Prophylactic administration of G-CSF and L resulted in a clinically relevant reduction of the incidence and severity of SG-related neutropenia and diarrhea and limited AE related dose reductions/interruptions and treatment discontinuations. Clinical trial information: NCT05520723 .