Abstract PD11-09: PD11-09 Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): updated results from BEGONIA, a phase 1b/2 study
Authors: Schmid Peter , Wysocki Piotr , Ma Cynthia , Park Yeon H. , Fernandes Ricardo , Lord Simon , Baird Richard D. , Prady Catherine , Jung Kyung Hae , Asselah Jamil , Huisden Robert , Stewart Ross , Vuković Petra , Nunes Ana T. , Nowecki Zbigniew 
Published: March 2023

Abstract
Background: Patients with a/mTNBC have limited treatment options and a poor prognosis (objective response rate [ORR] of 37%, median duration of response 6.5 months, median overall survival 15.5 months for 1L chemotherapy [Rugo, et al. Ann Oncol. 2021 LBA16]). Combining checkpoint inhibitors with 1L chemotherapy modestly improves outcomes but only in PD-L1–positive a/mTNBC, emphasizing a critical unmet need for patients with PD-L1–negative disease and for further improving outcomes in PD-L1–positive disease. BEGONIA (NCT03742102) is an ongoing 2-part, open-label platform study, evaluating safety and efficacy of D, an anti–PD-L1 antibody, combined with other novel therapies in 1L a/mTNBC, including Dato-DXd, an antibody-drug conjugate consisting of a humanized anti-TROP2 antibody covalently linked to a highly potent topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. Early data from BEGONIA of D in combination with Dato-DXd showed promising responses. Here, we report updated results of Dato-DXd + D. Methods: Patients with unresectable a/mTNBC eligible for 1L treatment were enrolled, regardless of PD-L1 or TROP2 status, and received intravenous Dato-DXd 6 mg/kg + D 1120 mg every 3 weeks until progression or unacceptable toxicity. PD-L1, assessed using the VENTANA PD-L1 (SP263) Assay, was defined as high if ≥ 5% of the tumor area was populated by PD-L1–expressing tumor or immune cells. Primary endpoints were safety and tolerability. Secondary endpoints included investigator-assessed ORR (RECIST v1.1) and duration of response. Patients included in the efficacy analysis had ≥ 2 on-treatment disease assessments, progressed, died, or withdrew from the study. Results: As of April 8, 2022, 47 patients received Dato-DXd + D (39 ongoing) and 33 of those were included in the efficacy analysis. Median (range) follow-up was 7.5 (0–11) months. Patient age was a median of 51 years, 57% received prior treatment for early stage TNBC, and 60% had visceral metastases at baseline. Confirmed ORR was 26/33 (79%; 95% CI, 61–91); 2/33 patients (6%) had a complete response and 24/33 (73%) had a partial response. Confirmed response was irrespective of PD-L1 expression (PD-L1 high ORR, 4/5 [80%]; PD-L1 low, 16/21 [76%]; PD-L1 missing, 6/7 [86%] patients). Median duration of response was not reached; 100% of patients with a complete or partial response remained in response at 6 month follow-up, and 96% had an ongoing response at data cutoff. Adverse events (AEs) were manageable and consistent with the known safety profiles of each agent, with treatment-related AEs occurring in 41 patients (87%), any Grade 3/4 AEs in 17 patients (36%), and any serious AEs in 7 patients (15%). The most common all-Grade AEs were gastrointestinal (nausea in 26 patients [55%] and stomatitis in 24 patients [51%]). A low rate of diarrhea was reported (6 patients [13%], all Grade 1 or 2); 4 patients had anemia and 1 had neutropenia. There were no cases of interstitial lung disease/pneumonitis or thrombocytopenia. Nine patients (19%) and 11 patients (23%) underwent Dato-DXd dose reduction and delay, respectively; 14 (30%) had D dose delay. Treatment was discontinued due to an AE for 3 patients (6%). There were no deaths due to treatment-related AEs. Conclusions: In this updated analysis with additional patients and longer follow-up, the combination of Dato-DXd + D in 1L a/mTNBC demonstrated a manageable safety profile and compelling high response rates with promising durability. Although subgroups were small, responses occurred irrespective of PD-L1 expression. Further investigation of this treatment combination is warranted. Analysis of translational data is ongoing. Funding: AstraZeneca/Daiichi Sankyo
Citation Format: Peter Schmid, Piotr Wysocki, Cynthia Ma, Yeon H. Park, Ricardo Fernandes, Simon Lord, Richard D. Baird, Catherine Prady, Kyung Hae Jung, Jamil Asselah, Robert Huisden, Ross Stewart, Petra Vuković, Ana T. Nunes, Zbigniew Nowecki. PD11-09 Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): updated results from BEGONIA, a phase 1b/2 study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-09.