LBA55 - Trastuzumab deruxtecan (T-DXd) in patients (Pts) with HER2-mutant metastatic non-small cell lung cancer (NSCLC): Interim results from the phase 2 DESTINY-Lung02 trial

Background

In DESTINY-Lung01, T-DXd 6.4 mg/kg (a HER2-targeting antibody-drug conjugate) showed durable activity in pts with previously treated HER2-mutant (HER2m) NSCLC (Li et al. N Engl J Med 2022). DESTINY-Lung02 assessed the benefit-risk profile of T-DXd doses 5.4 and 6.4 mg/kg in pts with previously treated HER2m metastatic NSCLC (NCT04644237). Here we report interim results for DESTINY-Lung02.

Methods

This was a blinded, randomized, non-comparative, phase 2 trial. Pts were randomized 2:1 to T-DXd 5.4 or 6.4 mg/kg Q3W, respectively. The primary endpoint was confirmed objective response rate (cORR) by blinded independent central review (BICR). Secondary endpoints included duration of response (DoR) by BICR, confirmed disease control rate (cDCR) and safety. The prespecified early cohort (PEC; pts randomized ≥4.5 months [mo] before data cutoff [DCO]) was defined to include pts with postbaseline tumor assessments. The safety analysis set (SAS) was all randomized pts who received ≥1 dose of T-DXd. The study was not powered to statistically compare the doses.

Results

At DCO (03/24/2022), 52 and 28 pts in the PEC were randomized and 101 and 50 pts in the SAS were treated with T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up duration was 5.6/5.4 mo and 3.8/3.9 mo. In the PEC, cORR was 53.8% (95% CI, 39.5-67.8%) and 42.9% (95% CI, 24.5-62.8%) in pts receiving T-DXd 5.4 or 6.4 mg/kg, respectively (Table). Treatment-emergent adverse events (TEAEs) were higher with T-DXd 6.4 mg/kg vs 5.4 mg/kg in the PEC and SAS (median treatment duration: 4.7/5.5 mo and 3.3/3.7 mo). In the SAS, any-grade adjudicated drug-related interstitial lung disease occurred in 5.9% and 14.0% of pts receiving T-DXd 5.4 or 6.4 mg/kg, respectively. Table: LBA55

T-DXd in HER2m NSCLC

^†Proportion of pts w/ confirmed CR or PR by BICR.^‡Proportion of pts w/ confirmed CR, PR, or SD by BICR.

Conclusions

DESTINY-Lung02 demonstrated clinically meaningful activity with T-DXd 5.4 mg/kg and 6.4 mg/kg in pts with previously treated HER2m NSCLC in the PEC, with a more favorable safety profile with T-DXd 5.4 mg/kg.

Clinical trial identification

NCT04644237.

Editorial acknowledgement

Under the guidance of authors, assistance in medical writing and editorial support was provided by Selene Jarrett, PhD, of ApotheCom, and was funded by Daiichi Sankyo.

Legal entity responsible for the study

Daiichi Sankyo and AstraZeneca.

Funding

Daiichi Sankyo and AstraZeneca.

Disclosure

K. Goto: Financial Interests, Personal, Invited Speaker: Amgen Inc., Amgen K.K., Amoy Diagnosties Co.,Ltd., AstraZeneca K.K., Bayer U.S., 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., Guardant Health Inc., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K.; Financial Interests, Personal, Expert Testimony: Medpace Japan K.K.; 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., Kyowa Kirin Co., Ltd., Loxo Oncology, Inc., Medical ＆ Biological Laboratories Co., LTD., Merck Biopharma Co., Ltd., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sumitomo Dainippon Pharma Co., Ltd., Spectrum Pharmaceuticals, Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics,Inc.; Non-Financial Interests, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. K. Sang-We: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Novartis, Takeda, Yuhan; Financial Interests, Personal, Speaker’s Bureau, Expert Testimony: Boehringer Ingelheim; Financial Interests, Personal, Research Grant: Yuhan. T. Kubo: Financial Interests, Personal, Other, Honoraria: AstraZeneca. 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, Institutional, Invited Speaker: Bristol Myers Squibb, DaiichiSankyo, Eli Lilly, Guardant Health, Preferred Network; Financial Interests, Personal and Institutional, Invited Speaker: Chugai, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Prefered Network. M. Ahn: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Daichii Sankyo, Yuhan, Amgen, Eli Lilly, TAKEDA, MSD, Merck, Pfizer, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Alpha-pharmaceuticals, Eli Lilly, Takeda, Merck, MSD, Amgen, Yuhan, Daichii Sankyo, Roche, Pfizer, Arcus. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen; Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre; Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. D. Kim: Financial Interests, Personal, Other, Travel Expenses: Amgen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Xcovery, Merck, Janssen, Hanmi, GSK, Daiichi Sankyo, Chong Keun Dang, Bridge BioTherapeutics, BMS, Boehringer-Ingelheim, AstraZeneca/Medimmune, Amgen, Alpha Biopharma, Novartis, Mirati Therapeutics, Merus, MSD, ONO Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Yuhan. J.C. Yang: Financial Interests, Institutional, Advisory Board: AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Amgen, Novartis, Bayer, GSK, Takeda Oncology, Puma Pharmaceuticals, Ono Pharmaceuticals, Merck Serono, MSD, Pfizer, Eli Lilly, Roche/Genentech, Janssen; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Novartis, AstraZeneca, MSD, Ipsen, Takeda Oncology; Financial Interests, Personal, Advisory Board: Yuhan Pharmaceuticals; Financial Interests, Invited Speaker: Dizal Pharmaceutical, Novartis, Numab, Merck, Daiichi Sankyo, Eli Lilly, Bayer, Janssen; Non-Financial Interests, Leadership Role, Board of Director: IASLC; Non-Financial Interests, Member: ASCO. K.M.C. Pereira: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. K. Saxena: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. R. Shiga: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. Y. Cheng: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. M. Aregay: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares: 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; Financial Interests, Personal, Advisory Board, Consulting fees for advice on diagnostic development: Biocartis; 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.