166MO Datopotamab deruxtecan (Dato-DXd) + durvalumab (D) as first-line (1L) treatment for unresectable locally advanced/metastatic triple-negative breast cancer (a/mTNBC): Initial results from BEGONIA, a phase Ib/II study

Patients (pts) with a/mTNBC have limited treatment options and poor prognosis. Combining checkpoint inhibitors with 1L chemotherapy improves outcomes but only in PD-L1+ve a/mTNBC, emphasizing a critical need. Dato-DXd, a TROP2 antibody-drug conjugate (ADC) with potent topoisomerase (TOPO) I inhibitor payload, elicited a 34% objective response rate (ORR) in heavily pretreated a/mTNBC and 52% ORR in a subset naïve to TOPO I-based ADCs. In BEGONIA, an ongoing 2-part, open-label platform study, D (an anti-PD-L1 antibody) combined with other therapies, including ADCs, is being evaluated in 1L a/mTNBC (NCT03742102). Here, we report preliminary results of Dato-DXd + D. Unresectable a/mTNBC pts eligible for 1L treatment, regardless of PD-L1/TROP2 status, received intravenous Dato-DXd 6 mg/kg + D 1120 mg every 3 weeks until progression or unacceptable toxicity. Primary endpoints are safety and tolerability. Secondary endpoints include investigator-assessed ORR (RECIST v1.1) and response duration. Data cutoff was Nov 2021. 29 pts received Dato-DXd + D (24 ongoing), 27 had the opportunity to have 2 postbaseline scans. Median (range) follow-up was 3.9 (2–6) months. Confirmed ORR was 20/27 (74%; 95% CI, 54–89); 2 (7%) pts had complete and 18 (67%) had partial responses, all were in response at data cutoff. No dose-limiting toxicities were observed. 4 pts (14%) underwent 1 Dato-DXd dose reduction due to stomatitis, 4 (14%) had 1 Dato-DXd dose delay, and 4 (14%) had 1 D dose delay. No dose modifications were required due to diarrhea.Table: 166MOSummary of adverse events (AEs), n (%)Dato-DXd + D, N=29Any grade AEsa29 (100)Grade 3/4 AEs8 (28)Grade 5 AEs0Serious AEs5 (17)Treatment-related AEsb27 (93)Grade 3/48 (28)Discontinued treatment due to AEc2 (7)aFrequent AEs were stomatitis (69%), nausea (66%), and alopecia (66%). Diarrhea occurred for 4 patients (14%; all Grade 1), and there were no cases of ILD/pneumonitis or neutropenic events (neutropenia or neutrophil count decreased).bPossibly related to D, Dato-DXd, or both. Frequent treatment-related AEs were stomatitis (69%), nausea (62%), and alopecia (59%).cIncludes 1 case of anaphylactic reaction and 1 case of troponin increase. Open table in a new tab aFrequent AEs were stomatitis (69%), nausea (66%), and alopecia (66%). Diarrhea occurred for 4 patients (14%; all Grade 1), and there were no cases of ILD/pneumonitis or neutropenic events (neutropenia or neutrophil count decreased). bPossibly related to D, Dato-DXd, or both. Frequent treatment-related AEs were stomatitis (69%), nausea (62%), and alopecia (59%). cIncludes 1 case of anaphylactic reaction and 1 case of troponin increase. Combination of Dato-DXd + D in 1L a/mTNBC demonstrated robust response rates with a manageable safety profile in this preliminary analysis, warranting further investigation. Additional enrollment and analysis of translational data is ongoing. Funding: AstraZeneca/Daiichi Sankyo.