LUNG CANCER—NON-SMALL CELL METASTATIC

9004 Oral Abstract Session

TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro)

with or without platinum chemotherapy (Pt-CT) in advanced non-small cell lung cancer
(aNSCLC).

Yasushi Goto, Wu-Chou Su, Benjamin Philip Levy, Olivier Rixe, Tsung-Ying Yang, Anthony W. Tolcher,
Yanyan Lou, Yoshitaka Zenke, Panos Savvides, Enriqueta Felip, Manuel Domine,
Konstantinos Leventakos, Mariano Provencio, Atsushi Horiike, Edward Pan, Daisy Lin, Jessie Gu,
Priyanka Basak, Michael Jon Chisamore, Luis G. Paz-Ares; National Cancer Center Hospital, Tokyo,
Japan; Department of Oncology, National Cheng Kung University, Tainan, Taiwan; The Sidney Kimmel
Comprehensive Cancer Center at Johns Hopkins Medicine, Baltimore, MD; Daiichi Sankyo Inc.,
Basking Ridge, NJ; Division of Chest Medicine, Taichung Veterans General Hospital, Taichung,
Taiwan; NEXT Oncology, San Antonio, TX; Mayo Clinic, Jacksonville, FL; Department of Thoracic
Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Mayo Clinic, Phoenix, AZ; Vall
d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain; De-
partment of Oncology, Hospital Universitario Fundación Jiménez Dı́az (IIS-FJD), Madrid, Spain; Mayo
Clinic, Rochester, MN; Department of Medical Oncology, Hospital Universitario Puerta de Hierro-
Majadahonda, Madrid, Spain; Department of Thoracic Medical Oncology, The Cancer Institute Hospital
of Japanese Foundation for Cancer Research, Tokyo, Japan; Merck & Co., Inc., Rahway, NJ; Hospital
Universitario 12 de Octubre, CNIO-H120 Lung Cancer Unit, Ciberonc and Universidad Complutense,
Madrid, Spain

Background: Despite advances in first-line (1L) immunotherapy 6 CT, most patients (pts) with aNSCLC
experience disease progression, necessitating novel strategies. Dato-DXd is an antibody drug conjugate
(ADC) composed of a humanized anti-TROP2 IgG1 monoclonal antibody covalently linked to a
topoisomerase I inhibitor payload via a plasma-stable tetrapeptide-based cleavable linker. Dato-
DXd had encouraging efficacy and manageable safety in heavily pretreated aNSCLC. Dato-DXd +
immunotherapy yielded greater preclinical activity than either agent alone. Methods: TROPION-Lung02
(NCT04526691) is a phase 1b, global, dose-escalation and -expansion study evaluating Dato-DXd (4 or
6 mg/kg) + pembro 200 mg 6 Pt-CT (cisplatin 75 mg/m2 or carboplatin AUC 5) every 21 days across 6
cohorts. Pts in escalation may have received #2 prior lines of therapy for aNSCLC. Pts in expansion
were primarily treatment (tx) naive (pts receiving Dato-DXd + pembro may have #1 prior Pt-based tx).
The primary objective is to assess safety and tolerability, including dose-limiting toxicities (DLTs).
Secondary objectives include evaluation of efficacy, pharmacokinetics, and immunogenicity. Results:
As of the Oct 31, 2022, data cutoff (DCO), 120 pts were treated. All cohorts met DLT criteria to move to
escalation. Median age was 65 years. PD-L1 expression was ,1%, 1%-49%, and $50% in 40%, 33%,
and 26% of pts, respectively. Median tx duration was 4.6 mo, with 55% receiving tx at DCO. The most
frequent any-grade (gr) tx-emergent adverse events (TEAEs) were nausea (45%) and stomatitis (45%).
Gr $3 TEAEs occurred in 61% of pts; most frequent were neutrophil count decreased (8%) and
amylase increased (8%). TEAEs that were serious, associated with discontinuation, or associated with
death occurred in 31%, 24% (16% associated with Dato-DXd), and 6% of pts, respectively. Dose
reductions due to TEAEs associated with Dato-DXd occurred in 17%. Drug-related interstitial lung
disease occurred in 12 pts (10%; 9 gr 1/2; 3 gr 3). The objective response rate (ORR) with 1L Dato-DXd
+ pembro doublet and Dato-DXd + pembro + Pt-CT triplet tx was 60% (95% CI, 36%-81%; 12 [2
unconfirmed]/20) and 55% (95% CI, 39%-70%; 23 [5 unconfirmed]/42), respectively. The ORR for
any line of therapy was 38% (95% CI, 25%-54%; 18 [2 unconfirmed]/47) with doublet and 47% (95%
CI, 34%-60%; 28 [5 unconfirmed]/60) with triplet tx. In both subsets, the disease control rate was
85% and median duration of response was not reached. Responses were observed in all 3 PD-L1
expression level subgroups. Although immature, median progression-free survival (95% CI) was 10.8
(8.3-15.2) and 7.8 mo (5.5-NE) with doublet and triplet tx, respectively. Conclusions: Dato-DXd +
pembro 6 Pt-CT demonstrated tolerable safety with notable 1L activity in this first and largest dataset
with an ADC + immunotherapy 6 Pt-CT in aNSCLC pts. Clinical trial information: NCT04526691.
Research Sponsor: Daiichi Sankyo, Inc.

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