Abstract 7P
Background
The HER2-targeted antibody-drug conjugate (ADC) T-DXd demonstrated efficacy in heavily pretreated HER2-over- and -low expressing ABC. We aimed to assess the activity of T-DXd in HER2-over/low expressing or IHC-0 ABC, to describe the drug mechanisms of action and to identify biomarkers associated to drug response or resistance.
Methods
DAISY is an open-label phase II trial to assess the efficacy of T-DXd in ABC with extensive biomarkers analysis (1) in 3 cohorts: Cohort 1 (HER2 over-expressing: 3+ on IHC or ISH+), Cohort 2 (HER2 low-expressing: 1+ or 2+/ISH-) and cohort 3 (HER2-IHC 0). The primary endpoint was the confirmed objective response rate (ORR). Secondary endpoints were clinical benefit rate, duration of response (DOR), progression-free (PFS), overall survival (OS) and safety. Here we report clinical activity and safety with a longer follow-up of 38.4 months [95%CI: 35.3-40.9].
Results
185 women and 1 man were enrolled between 2019 and 2021. Among the safety population (179 pts), median [range] age was 55 [24-82] years, median number of previous metastatic line was 5 [0-17] and 12 pts harbored triple-negative ABC. Median number of cycles was 10 [1-63]. In December 2023, 6 pts were still on-treatment. The table shows T-Dxd activity in the full analysis set population (177 pts). Important to note, PFS rate at 24 months was 31% [95%CI: 20-43] in cohort 1. A total of 173 pts (96.6%) had at least one treatment-related adverse event (TRAE). Eight pts (4.5%) had drug related ILD or pneumonitis (grade (G) 1 in 6 pts, G2 and G5 in 1 pt each), 18 pts discontinued treatment due to TRAEs. Table: 7P
| Total | Cohort 1 | Cohort 2 | Cohort 3 | |
| BOR confirmed n/N [95%CI] | 86/177 (48.6%) [41.0; 56.2] | 48/68 (70.6%) [58.3; 81.0] | 27/72 (37.5%) [26.4; 49.7] | 11/37 (29.7%) [15.9; 47.0] |
| Median DOR (months) [95%CI] | 8.5 [6.8; 9.7] | 9.7 [7.2; 17.9] | 7.6 [4.4; 9.4] | 6.8 [2.8; 17.5] |
| Median PFS (months) [95%CI] | 7.1 [6.6; 8.7] | 11.1 [8.5; 14.4] | 6.8 [4.6; 8.5] | 4.2 [2.0; 5.7] |
| Median OS (months) [95%CI] | 19.6 [16.1; 22.3] | 31.2 [22.4; Not Reached] | 19.3 [11.5; 22.1] | 12.1 [8.3; 15.0] |
Conclusions
Consistent with previously reported data, T-DXd showed clinically meaningful activity in pts with HER2-overexpressing ABC and antitumour activity in those with HER2-low and non-expressing ABC during extended follow-up. Safety profile was consistent with previous reports. (1) Mosele F and alNat Med 2023
Clinical trial identification
NCT04132960.
Legal entity responsible for the study
Unicancer.
Funding
Daiichi Sankyo.
Disclosure
V.C. Dieras: Financial Interests, Personal, Advisory Board, National advisory board: Pierre Fabre Oncologie; Financial Interests, Personal, Advisory Board, Steering Committee, consultant, Symposium, travel expenses: Roche Genentech; Financial Interests, Personal, Advisory Board, + Symposia and travel expenses: Novartis; Financial Interests, Personal, Advisory Board, Advisory boards, symposia, travel expenses: Pfizer; Financial Interests, Personal, Advisory Board, Symposia, travel expenses: Lilly, AstraZeneca, MSD; Financial Interests, Personal, Advisory Board, Symposia,travel expenses: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, symposia,travel expenses: Seagen, Gilead; Financial Interests, Personal, Advisory Board, Steering Committee: AbbVie; Financial Interests, Personal, Advisory Board: Eisai, Medac GmbH; Financial Interests, Personal, Other, IDMC: Sanofi; Financial Interests, Personal, Advisory Board, national board: Menarini; Financial Interests, Personal and Institutional, Other, IDMC: Sanofi; Financial Interests, Institutional, Invited Speaker: Roche Genentech, AstraZeneca; Financial Interests, Institutional, Invited Speaker, Steering Committee: Lilly; Financial Interests, Institutional, Invited Speaker, + IDMC: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, PI: Seagen. F. André: Financial Interests, Personal, Advisory Board: Lilly France; Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, Roche, Lilly, Pfizer, Owkin, Novartis, Guardant Health, N-Power Medicine, Servier, Gilead, Boston Pharmaceutics; Financial Interests, Institutional, Research Grant: AstraZeneca, Lilly, Novartis, Pfizer, Roche, Daiichi, Guardant Health, Owkin. B. Pistilli: Financial Interests, Institutional, Advisory Board: AstraZeneca, Seagen, Lilly, Daiichi Sankyo, MSD; Financial Interests, Institutional, Invited Speaker: Gilead, Novartis, AstraZeneca, AstraZeneca, Gilead, Seagen, MSD, Novartis, Novartis; Financial Interests, Personal, Advisory Board: Pierre Fabre, Daiichi Sankyo; Financial Interests, Personal, Other, travel support: AstraZeneca, Pierre Fabre, MSD, Daiichi Sankyo; Financial Interests, Personal, Other, Travel support: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Funding: Daiichi Sankyo; Non-Financial Interests, Project Lead: Unicancer. T. Bachelot: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Pfizer, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Advisory Board: Lilly; Financial Interests, Institutional, Research Grant: Novartis, Roche, AstraZeneca, Seagen, Pfizer; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Principal Investigator: Roche, AstraZeneca. J. Pierga: Financial Interests, Personal, Advisory Board: Pfizer, Lilly, Seagen, MSD, Novartis, Exact Sciences, Gilead, AstraZeneca, Eisai; Financial Interests, Personal, Invited Speaker: Roche, Daiichi Sankyo, Menarini, Veracyte, Pfizer, Lilly, Seagen, MSD, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Novartis, Daiichi Sankyo; Financial Interests, Institutional, Other, IDMC: Sanofi; Financial Interests, Institutional, Funding: Servier. C. Levy: Non-Financial Interests, Personal, Other, Medical Symposium: Gilead, Pfizer; Financial Interests, Institutional, Sponsor/Funding: Lilly; Non-Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo, Novartis, Roche. C. Jouannaud: Financial Interests, Personal, Advisory Board: Daiichi Sankyo AstraZeneca. P. Fournel: Financial Interests, Personal, Advisory Board: BMS, Sanofi, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Amgen; Financial Interests, Personal, Other, Congress invitation: Takeda; Financial Interests, Institutional, Invited Speaker: BMS, Ipsen. C. Mahier Ait Oukhatar: Financial Interests, Institutional, Funding: Daiichi Sankyo. T. Filleron: Financial Interests, Personal, Other, working group: Janssen-Cilag,; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Other, working group: Roche; Other, Consulting (compensated to my institution): Cellectis. M.F. Mosele: Financial Interests, Institutional, Invited Speaker: Novartis; Financial Interests, Personal, Full or part-time Employment: PEGASCY. M. Lacroix-Triki: Financial Interests, Personal, Advisory Board, invited speaker: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Board, invited speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Roche diagnostics. All other authors have declared no conflicts of interest.