379MO - 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 Ib/II study

Background

BEGONIA (NCT03742102) is an ongoing 2-part, open-label platform study in 1L a/mTNBC, evaluating D, an anti–PD-L1 antibody, plus novel therapies, including Dato-DXd, an antibody-drug conjugate made of a anti-TROP2 antibody covalently linked via a cleavable linker to a topoisomerase I inhibitor payload. Early data from BEGONIA Arm 7, Dato-DXd + D, showed promising responses. Updated results, including response duration (DoR), are reported.

Methods

Patients (pts) with unresectable a/mTNBC eligible for 1L treatment were enrolled, regardless of PD-L1/TROP2 expression, and received Dato-DXd 6 mg/kg IV + D 1120 mg IV Q3W until progression or unacceptable toxicity. PD-L1, assessed by the VENTANA PD-L1 (SP263) Assay, was high if ≥10% 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, PFS (RECIST v1.1), and DoR.

Results

As of 2 Feb 2023, 62 pts received Dato-DXd + D (29 ongoing). Median follow-up was 11.7 (range 2–20) months (mos). At baseline, median pt age was 53 years; 60% had visceral metastases; 87% had PD-L1–low expression. Confirmed ORR was 79% (95% CI, 67–88); 6 (10%) pts had complete and 43 (69%) had partial responses. Response to treatment was irrespective of PD-L1 expression level. Median DoR was 15.5 mos (95% CI, 9.9–not calculable [NC]). Median PFS was 13.8 mos (95% CI, 11–NC). Nausea and stomatitis were the most common adverse events (AEs; 40 [65%] each). Any Grade (G) 3/4 AEs occurred in 35 (57%) pts and serious AEs in 14 (23%). Low rates of anemia (9 [15%]), diarrhea (8 [13%]), and neutropenia (3 [5%]) occurred. Adjudicated treatment-related interstitial lung disease/pneumonitis occurred in 3 (5%) pts (2 G2; 1 G1). No deaths due to treatment-related AEs occurred. 10 (16%) pts discontinued any study drug due to AEs. No new safety signals were reported.

Conclusions

Dato-DXd combined with D continues to demonstrate manageable safety and compelling high, durable response rates in 1L a/mTNBC. Further investigation is warranted. Translational data analysis is ongoing. Funding: AstraZeneca/Daiichi Sankyo.

Clinical trial identification

NCT03742102; November 15, 2018.

Editorial acknowledgement

Medical writing and editorial support, which was in accordance with Good Publication Practice ( GPP 2022 ) guidelines, was provided by Nicole Seneca, PhD, of Parexel and was funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca/Daiichi Sankyo.

Funding

AstraZeneca/Daiichi Sankyo.

Disclosure

P. Schmid: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Novartis, Pfizer, Roche, Puma Biotechnology; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting or Advisory Role: AstraZeneca, Bayer, Boehringer Ingelheim, Celgene, Eisai, Roche, Merck, Novartis, Pfizer, Puma Biotechnology; Financial Interests, Institutional, Research Funding: Astellas Pharma, AstraZeneca, Medivation Inc, OncoGenex; Financial Interests, Personal, Research Funding: Genentech, Novartis, Roche. P.J. Wysocki: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Astellas, Amgen, BMS, Gilead, IPSEN, Immunicom, Janssen, MSD, Merck, Pierre Fabre, Pfizer, Roche, Sanofi; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting or Advisory Role: AstraZeneca, Astellas, Amgen, BMS, IPSEN, Immunicom, Janssen, MSD, Merck, Pierre Fabre, Pfizer, Roche, Sanofi; Financial Interests, Institutional, Research Funding: Immunicom, Merck, Pierre Fabre, Roche. C.X. Ma: Financial Interests, Institutional, Research Funding: Puma, Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting Fees: AstraZeneca, Natera, Biovica, Novartis, Sanofi, Pfizer. Y.H. Park: Financial Interests, Personal, Other, Honoraria: Merck, Novartis, Pfizer; Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting or Advisory Role: AstraZeneca, Daiichi Sankyo, Eisai, Pfizer, Roche; Financial Interests, Institutional, Research Funding: AstraZeneca, Merck, Novartis, Pfizer; Financial Interests, Personal, Other, Travel, accommodation, expenses: Merck, Novartis. R. Fernandes: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting Fees: Canadian Agency for Drugs and Technologies in Health (CADTH); Financial Interests, Personal, Other, Honoraria: Bayer, Pfizer, Ipsen, BMS, Merck, Novartis, and Janssen . S. Lord: Financial Interests, Institutional, Other, Reports funding for clinical trial activities from AstraZeneca, during the conduct of the study: AstraZeneca; Financial Interests, Personal, Other, Honoraria: Eisai, Prosigna, and Roche; Financial Interests, Personal, Advisory Board: Shionogi; Financial Interests, Institutional, Research Grant: Pathios Therapeutics; Financial Interests, Personal, Other, Travel, accommodation, and expenses paid by Piqur Therapeutics, Pfizer, Roche, and Synthon, outside the submitted work: Piqur Therapeutics, Pfizer, Roche, and Synthon; Financial Interests, Personal, Other, Dr Lord holds patents associated with his role as cofounder of Mitox Therapeutics: Mitox Therapeutics. R.D. Baird: Financial Interests, Institutional, Research Funding: AstraZeneca, Boehringer-Ingelheim, Carrick Therapeutics, Genentech, G1T Therapeutics, Janssen, Molecular Partners, Roche, Shionogi, Taiho; Financial Interests, Institutional, Speaker, Consultant, Advisor, Consulting or Advisory Role: AstraZeneca, Daiichi Sankyo, Molecular Partners, Novartis, Roche. C. Prady: Financial Interests, Institutional, Research Funding, Clinical Trial Activity: AstraZeneca, Sanofi, Roche, Novartis. K.H. Jung: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting or Advisory Role: AstraZeneca, Celgene, Eisai, MSD, Novartis, Pfizer, Roche, Takeda, Daiichi Sankyo, Bixink, Everest Medicine. J. Asselah: Financial Interests, Personal, Speaker, Consultant, Advisor, Consulting or Advisory Role: AstraZeneca, Pfizer, Eisai, Novartis, BMS. R. Huisden, K. Heider, P. Vukovic, N. Denduluri: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. R. Stewart: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Other, Reports personal fees from AstraZeneca and Pfizer, outside the submitted work: AstraZeneca, Pfizer.. Z. Nowecki: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Sanofi-Aventis, MSD, Roche.