1507TiP - Phase Ib multicenter study of trastuzumab deruxtecan (T-DXd) and immunotherapy with or without chemotherapy in first-line treatment of patients (pts) with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) and HER2 overexpression (OE): DESTINY-Lung03

Background

T-DXd is a HER2-directed antibody-drug conjugate available for the treatment of pts with metastatic NSCLC with activating HER2 mutations, HER2+ breast or gastric cancer, or HER2-low breast cancer. DESTINY-Lung01 showed efficacy of T-DXd monotherapy in heavily pretreated pts with unresectable/metastatic, HER2-OE, nonsquamous NSCLC. In preclinical studies, the combination of T-DXd and immunotherapy was more effective than either therapy alone, and the addition of chemotherapy may improve efficacy. This trial is evaluating T-DXd alone or in combination with durvalumab (durva) or MEDI5752 (a PD-1/CTLA-4 bispecific antibody) with or without chemotherapy in pts with unresectable/metastatic, HER2-OE, nonsquamous NSCLC.

Trial design

DESTINY-Lung03 (NCT04686305) is a phase 1b, open-label, multicenter, dose-escalation and -expansion study in pts with HER2-OE unresectable, locally advanced or metastatic, nonsquamous NSCLC. In part 1 (enrollment completed), pts with disease progression after 1 or 2 lines of systemic therapy in the recurrent/metastatic setting receive T-DXd monotherapy or T-DXd + durva in combination with cisplatin, carboplatin, or pemetrexed. Part 2 of the trial was not initiated. In part 3, pts who have not received prior treatment for advanced or metastatic disease will receive T-DXd in combination with MEDI5752, with or without carboplatin; pts in this phase must not have a history of prior immunotherapy for early disease and must lack activating EGFR mutations, an EML4-ALK fusion, or other targetable alterations. The primary endpoint is the frequency of adverse events (AEs) and serious AEs (SAEs) with T-DXd + durva + chemotherapy (part 1) or T-DXd + MEDI5752 ± chemotherapy (part 3). Secondary endpoints include confirmed objective response rate, duration of response, disease control rate, progression-free and overall survival, pharmacokinetics, and immunogenicity in all arms as well as the frequency of AEs and SAEs with T-DXd monotherapy (part 1).

Clinical trial identification

NCT04686305.

Editorial acknowledgement

Medical writing support was provided by Articulate Science, LLC, and was funded by AstraZeneca in accordance with Good Publication Practice (GPP) guidelines.

Legal entity responsible for the study

AstraZeneca and Daiichi Sankyo.

Funding

AstraZeneca in collaboration with Daiichi Sankyo.

Disclosure

D. Planchard: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Janssen, AbbVie, Seagen, Gilead; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Janssen, AbbVie; Financial Interests, Personal, Other, meetings and/or travel: AstraZeneca, Roche, Novartis, Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche, Janssen, AbbVie; Financial Interests, Institutional, Other, Clinical trials research as principal or co-investigator: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, Janssen, AbbVie. J.R. Brahmer: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Eli Lilly, Merck, Amgen, Genentech, GSK, AstraZeneca, Regeneron, Sanofi; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Bristol Myers Squibb, Roche/Genentech; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, AstraZeneca, Spectrum Pharmaceuticals, Revolution, Rapt Therapeutics, Genentech/Roche. J.C. Yang: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Novartis, AstraZeneca, Clovis Oncology, Eli Lilly, MSD Oncology, Merck Serono, Celgene, Bayer, Pfizer, Ono Pharmaceutical, Bristol Myers Squibb, Yuhan, Hansoh, Blueprint Medicines, Daiichi Sankyo, G1 Therapeutics, AbbVie, Takeda, Amgen, Incyte; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim, Merck Serono, Janssen, GSK, Amgen, Takeda, Daiichi Sankyo, AstraZeneca, Novartis, MSD Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim, Roche, MSD, AstraZeneca, Novartis, Bristol Myers Squibb, Ono Pharmaceutical, Takeda, Eli Lilly, Pfizer. R.K. Li: Financial Interests, Institutional, Principal Investigator: AstraZeneca, Roche, Arcus, BeiGene; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, abstract writing or educational events: AstraZeneca, Roche, Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Eisai. J. Han: Financial Interests, Institutional, Research Funding: Pfizer, Ono, Takeda, Roche; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Amgen, AbbVie, Janssen, GSK, Gilead; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Janssen, Amgen, Novartis, Merck, Abion, J Ints Bio; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, abstract writing or educational events: AstraZeneca, Janssen, Merck, Yuhan, Novartis , Pfizer; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Membership or affiliation: ASCO, AACR, ESMO, KCA. D.L. Cortinovis: Financial Interests, Personal, Advisory Board, fee for consulting activity: MSD, BMS, Roche, Sanofi Genzyme, Amgen, AstraZeneca, Novartis. Y. Runglodvatana: Financial Interests, Personal, Principal Investigator: AstraZeneca, Roche, Arcus, BeiGene; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Eisai; Financial Interests, Personal, Other, attending meetings and/or travel: Eisai; Financial Interests, Personal, Advisory Board: AstraZeneca. E. Nakajima: Financial Interests, Personal, Full or part-time Employment: AstraZeneca, US Food and Drug Administration, MedStar Georgetown University; Financial Interests, Personal, Other, Support for attending meetings and/or travel: US Food and Drug Administration; Financial Interests, Personal, Membership or affiliation: ASCO. A. Ragone: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. M. Winter: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca. M. Gustavson: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks or ownership: AstraZeneca. All other authors have declared no conflicts of interest.