Abstract 132TiP
Background
No 1L HER2-directed therapies are currently approved for HER2-OE NSCLC, despite the disease being associated with poor prognosis. T-DXd (5.4 mg/kg) is approved in the US, Russia, Israel and Brazil for patients (pts) with unresectable or metastatic HER2-positive (immunohistochemistry [IHC] 3+) solid tumors after prior Tx and/or with no alternative Tx. DL-03 (NCT04686305) is a phase Ib, open-label, multipart study assessing T-DXd-based regimens in HER2-OE (IHC 3+/2+) NSCLC. DL-03 Part 1 results demonstrated the benefit of T-DXd monotherapy (5.4 mg/kg) in pretreated HER2-OE (IHC 3+/2+) metastatic NSCLC (ORR, 44%; median progression-free survival [PFS], 8.2 months; median overall survival [OS], 17.1 months). DL-03 Part 4 will assess 1L T-DXd + rilvegostomig (a novel anti-PD-1/TIGIT bispecific antibody that showed encouraging antitumor activity and an acceptable safety profile in pts with NSCLC in ARTEMIDE-01 [NCT04995523]) ± carboplatin in HER2-OE NSCLC.
Trial design
DL-03 Part 4 (safety run-in and expansion) will enroll pts with unresectable, locally advanced or metastatic HER2-OE NSCLC who have not received 1L Tx for advanced/metastatic disease. HER2 overexpression (≥25% of tumor cells with IHC 3+/2+ staining) will be assessed centrally. Pts with HER2 mutations, or other known genomic alterations/actionable driver kinases with approved therapies, are ineligible. Initially, T-DXd + rilvegostomig (Arm 4A) and T-DXd + rilvegostomig + carboplatin (Arm 4B) will be assessed in safety cohorts (≥6 pts randomized per arm). Following safety review, ~34 additional pts can be randomized to each arm (dose-expansion cohorts). Primary endpoints include adverse events (AEs; including serious AEs), AEs of special interest, and dose-limiting toxicities. Secondary endpoints include confirmed ORR, duration of response, disease control rate, and PFS by investigator per RECIST 1.1; and OS.
Clinical trial identification
NCT04686305.
Editorial acknowledgement
Under the guidance of authors, medical writing support was provided by Abbie Dodd, BSc, of Helios Medical Communications, part of Helios Global Group, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
This study is sponsored by 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
D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen, Seagen, Gilead, Pierre Fabre; Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen, Gilead, Seagen; Non-Financial Interests, Personal, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre, AbbVie, Sanofi, Janssen. J.C. Yang: Financial Interests, Institutional, Advisory Board: AbbVie, Amgen, AnHeart Therpeutics, ArriVent, AstraZeneca, Bayer, Black Diamond Therapeutics Inc., Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, GSK, Gilead, Janssen, MSD, Merck KGaA, Novartis, Ono Pharmaceuticals, Pfizer, Regeneron, Roche/Genentech, Takeda Oncology, Yuhan Pharmaceuticals; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Novartis; Financial Interests, Personal and Institutional, Invited Speaker, Travel to major meeting to present the trial results: AstraZeneca, Dizal Pharmaceutical; Financial Interests, Personal and Institutional, Invited Speaker, Travel to major meeting to present the trial result: Merck Sharp & Dohme Corporation; Financial Interests, Personal, Invited Speaker: Numab Therapeutics AG, Merck KGaA, Ipsen, Takeda Oncology, Daiichi Sankyo, Eli Lilly, Janssen Pharmaceuticals, ArriVent, Amgen, Bayer, Yuhan Pharmaceuticals, Black Diamond Therapeutics Inc.; Non-Financial Interests, Personal, Member: IASLC, ASCO. E. Nakajima, E. Schreffler, Y. Chang: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J.R. Brahmer: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Amgen, GSK, AstraZeneca, Sanofi, Janssen Oncology, Summit Therapeutics, Mestag Therapeutics, RAPT Therapeutics, Genmab; Financial Interests, Institutional, Funding: Bristol Myers Squibb, AstraZeneca; Financial Interests, Personal, Other: Bristol Myers Squibb, Merck, Regeneron.