510MO - Trastuzumab deruxtecan (T-DXd) in Asian patients (Pts) with human epidermal growth factor receptor 2 (HER2; ERBB2)-mutant (HER2m) metastatic non-small cell lung cancer (mNSCLC): Subgroup analysis of DESTINY–Lung02 (DL-02)

Background

In DL-02, T-DXd showed clinically meaningful activity in pts with previously treated HER2m mNSCLC (Goto et al. 2022). We present a regional prespecified subgroup analysis of Asian pts (93/152 pts) from DL-02.

Methods

Pts were randomized (2:1) to T-DXd 5.4 or 6.4 mg/kg every 3 weeks, respectively. Primary endpoint was confirmed objective response rate (cORR) by blinded independent central review (BICR). Key secondary endpoints were duration of response (DoR) by BICR, progression-free survival (PFS) by BICR, overall survival (OS), and safety. The study was not powered to statistically compare doses.

Results

At data cutoff (December 23, 2022), 63 and 30 Asian pts received T-DXd 5.4 or 6.4 mg/kg, respectively. With T-DXd 5.4 and 6.4 mg/kg, cORR (95% CI) was 50.8% (37.9-63.6) and 73.3% (54.1-87.7), median DoR was 16.8 months (mo) (7.1-not estimable [NE]) and NE (6.8-NE), median PFS was 10.8 mo (7.4-NE) and 15.4 mo (9.5-NE), and median OS was 19.5 mo (14.9-NE) and NE (12.1-NE), respectively. Median treatment duration was 8.4 mo with T-DXd 5.4 mg/kg and 8.5 mo with 6.4 mg/kg. With T-DXd 5.4 and 6.4 mg/kg, drug-related grade ≥3 treatment-emergent adverse events (TEAEs) were observed in 41.9% and 63.3% of pts, respectively; adjudicated drug-related interstitial lung disease (ILD) occurred in 12.9% and 40.0% of pts (no grade ≥3 events in both arms), and in 12.9% and 28.0% of pts in the overall population (Table).

Conclusions

In this descriptive subgroup analysis, both T-DXd doses showed strong and durable responses and manageable safety in Asian pts with previously treated HER2m mNSCLC. A numerically higher response with higher incidence of ILD was observed with T-DXd 6.4 mg/kg, whereas 5.4 mg/kg was associated with a lower ILD incidence and a more favorable benefit/risk profile, generally consistent with the overall population – supporting the use of T-DXd 5.4 mg/kg in Asian pts. Table: 510MO

Safety summary of T-DXd in DL-02

^aRandomized pts who received ≥1 T-DXd dose.

Clinical trial identification

NCT04644237.

Editorial acknowledgement

Under the guidance of authors, medical writing and editorial support were provided by Ilias Boltsis, PhD, and Caylin Bosch, PhD, of ApotheCom.

Legal entity responsible for the study

Daiichi Sankyo, Inc., and AstraZeneca.

Funding

This study was funded by Daiichi Sankyo, Inc., and AstraZeneca. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201).

Disclosure

Y. Goto: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, Guardant Health Inc., Illumina, MSD, Novartis, Ono Pharmaceutical, Pfizer, Taiho, Johnson and Johnson, D3bio; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Eli Lilly, MSD, Merck, Novartis, Ono Pharmaceutical, Pfizer, Taiho, Thermo Fischer; Financial Interests, Personal, Other, Travel Grant: Daiichi Sankyo; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Preferred Network; Financial Interests, Personal and Institutional, Coordinating PI: Chugai, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Prefered Network; Financial Interests, Institutional, Coordinating PI: Guardant Health; Non-Financial Interests, Personal, Member of Board of Directors: Cancer Net Japan, JAMT. K. Goto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Amoy Diagnosties Co., Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Guardant Health Inc., Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K., Taiho Pharmaceutical Co., Ltd., syneos health clinical K.K., Life Technologies Japan Ltd.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K., Medpace Japan K.K., Haihe Biopharma Co., Ltd.; Financial Interests, Personal and Institutional, Funding: Amgen Inc., Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ignyta,Inc., Janssen Pharmaceutical K.K., Kissei Pharmaceutical CO., LTD., Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Loxo Oncology, Inc., Medical&Biological laboratories CO., LTD., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics,Inc., Amgen Astellas BioPharma K.K., Bayer Yakuhin, Ltd., Blueprint Medicines Corporation., Craif Inc., Life Technologies Japan Ltd., NEC Corporation., Novartis Pharma K.K., Pfizer R&D Japan G.K., Turning Point Therapeutics,Inc.; Non-Financial Interests, Personal, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. T. Kubo: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical, Bristol Myers Squibb, Taiho Pharmaceutical, Kyowa Hakko Kirin, AstraZeneca, Ono Pharmaceutical, Nippon Kayaku, MSD, Pfizer, Lilly, Novartis, Boehringer Ingelheim, Towa Pharmaceutical. K. Ninomiya: Financial Interests, Personal, Speaker’s Bureau: Nippon Kayaku, Lilly Japan, Ono Pharmaceutical, AstraZeneca, Chugai Pharmaceuticals, Novartis, Kyowa Kirin, MSD KK, Takeda Pharmaceutical, Taiho Pharmaceutical, Bristol Myers Squibb, Janssen Pharmaceutical, Nippon Boehringer lngelheim, Erekta. S. Kim: Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Therapex; Financial Interests, Personal, Invited Speaker: Amgen, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Research Grant: Novartis, Yuhan. M. Ahn: Financial Interests, Personal, Advisory Board: AstraZeneca, TAKEDA, MSD, YUHAN, Amgen, ALPHA Pharmaceutical, Janssen, BMS, Roche, Daichi Sankyo, Merck, BOROnoI. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Bayer Yakuhin, Ltd., Incyte biosciences Japan, Merck Biopharma Co., Ltd., Janssen Pharmaceutical K.K., Bristol Myers Squibb Company, Medical Mobile Communications co., Ltd, Novartis Pharma K.K., Daiichi Sankyo Co., Ltd.; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K.; Financial Interests, Personal, Writing Engagement: YODOSHA CO., LTD.; Financial Interests, Institutional, Research Grant: Amgen Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., EP-CRSU CO., LTD., EPS Corporation., Nippon Kayaku Co., Ltd., Eisai Co., Ltd., GSK K.K., IQVIA Services JAPAN K.K., Janssen Pharmaceutical K.K., MSD K.K., Kobayashi Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Syneos Health Clinical K.K., Sanofi K.K., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., CMIC CO., Ltd., Pfizer R&D Japan G.K., Labcorp Development Japan K.K., Pfizer Japan Inc., Shionogi & Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Astellas Pharma Inc., Ascent Development Services, Eisai Inc., Bayer Yakuhin, Ltd, SRL Medisearch Inc., PRA HEALTHSCIENCES. H. Hayashi: Financial Interests, Personal, Invited Speaker: Guardant Health Japan Corp033., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., MSD K.K. J. Shimizu: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical Co., Ltd, Ono Pharmaceutical Co., Ltd, Takeda Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Lts, MSD, AstraZeneca, Novartis, Pfizer, Amgen. D. Kim: Financial Interests, Personal, Invited Speaker: Korean Cancer Association, Korean Society of Medical Oncology, Korean Association for Lung Cancer, Taiwan Lung Cancer Society, Japan Cancer Association; Financial Interests, Personal, Other, Scientific Advisor: HEALTH INSURANCE REVIEW & ASSESSMENT SERVICE, Korea; Financial Interests, Personal, Writing Engagement, Medical writing assistance: Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Chong Keun Dang, Daiichi Sankyo, GSK, Pfizer, MSD, Merck, Novartis, Roche, Takeda, Yuhan; Financial Interests, Institutional, Local PI, Clinical Trial Funding: Alpha Biopharma, Amgen, AstraZeneca/Medimmune, Boehringer Ingelheim, Daiich-Sankyo, Hanmi, Janssen, Merus, MIrati Therapeutics, MSD, Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, Yuhan, Bridge BioTherapeutics, GSK; Financial Interests, Institutional, Coordinating PI, Clinical Trial Funding: Chong Keun Dang; Financial Interests, Institutional, Research Grant, Laboratory research funding to my institution: InnoN; Non-Financial Interests, Personal, Advisory Role: Amgen, BMS / Ono Pharmaceuticals, Daiichi Sankyo, Janssen, GSK, Pfizer, AstraZeneca, SK Biopharm, Takeda, Yuhan; Non-Financial Interests, Personal, Member of Board of Directors: Korean Cancer Association, Korean Society of Medical Oncology, Korean Association for Lung Cancer, Asian Thoracic Oncology Research Group; Other, Personal, Other, Travel support for advisory board meeting attendance: Amgen, Daiichi Sankyo; Other, Personal, Other, Clinical trial research funding to my institution: Asian Thoracic Oncology Research Group. C.S. Kuo: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Roche, Pfizer, Eli Lilliy, Novartis, Ono Pharma, Chugai, Merck, Janssen Pharma, Takeda, Guardant Health; Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Eli Lilliy, Merck, Chugai, Takeda, Novartis, Guardant Health. K.H. Lee: Financial Interests, Personal, Advisory Board: BMS, Merck, MSD, AstraZeneca, Pfizer, Yuhan. K.M.C. Pereira: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. A. Taguchi: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. A. Ali: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. F. Cheng: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. R. Yonemochi: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. P.A. Jänne: Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Chugai Pharmaceuticals, Eli Lilly, Voronoi, Daiichi Sankyo, Novartis, Sanofi, Takeda Oncology, Mirati Therapeutics, Trasncenta, Silicon Therapeutics, Syndax, Nuvalent, Bayer, Esai, Allorion Therapeutics, Accutar Biotech, AbbVie, Duality Biologics; Financial Interests, Personal, Advisory Board, Consulting fees for advice on diagnostic development: Biocartis; Financial Interests, Personal, Advisory Board, Consulting fee for advice on drug development: Merus, Frontier Medicines; Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development.: Hongyun Biotechnology; Financial Interests, Personal, Stocks/Shares: Gatekeeper Pharmaceuticals, Allorion Therapeutics; Financial Interests, Personal, Royalties, I receive post-marketing royalties from being an inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp: Lab Corp; Financial Interests, Institutional, Research Grant, Sponsored research agreement with my institution: AstraZeneca, Daiichi Sankyo, PUMA, Eli Lilly, Boehringer Ingelheim, Revolution Medicines, Takeda Oncology. All other authors have declared no conflicts of interest.