Abstract 357P
Background
In the phase III TROPION-Lung01 study, Dato-DXd, a TROP2-directed antibody-drug conjugate, improved progression-free survival (PFS) vs docetaxel in pts with non-squamous (NSQ) a/mNSCLC. In a retrospective, exploratory analysis of TROPION-Lung01, QCS, a novel, fully supervised computational pathology approach that precisely locates and quantifies TROP2 was used. The analysis revealed that pts with TROP2 QCS-NMR+ tumors (TROP2 membrane expression relative to total TROP2 in membrane plus cytoplasm) treated with Dato-DXd had longer PFS and higher objective response rate (ORR) than pts with TROP2 QCS-NMR − tumors and pts who received docetaxel. In the phase I/II, open-label TROPION-PanTumor02 study, Dato-DXd (6 mg/kg Q3W) showed preliminary efficacy and tolerable safety in Chinese pts with a/mNSCLC. Here,we report the association of TROP2 QCS-NMR status with ORR and PFS from TROPION-PanTumor02.
Methods
Digitised TROP2 immunohistochemistry-stained whole-slide images of tissue samples from pts with NSCLC in TROPION-PanTumor02 were analysed by QCS. Samples were considered TROP2 QCS-NMR+ if ≥75% of tumour cells had NMR ≤0.56. Clinical primary analysis data cut-off was 9 Oct, 2023. Association of TROP2 QCS-NMR status with ORR and PFS was assessed.
Results
In total, 40 pts enrolled in the TROPION-PanTumor02 NSCLC cohort received Dato-DXd, 38 pts had samples evaluable for QCS (21 NSQ, 17 SQ). In total, 52.6% (20/38; 16/21 NSQ, 4/17 SQ) of tumor samples were identified as TROP2 QCS-NMR+. ORR was numerically higher (55.0% [95% CI 0.32, 0.77] vs 27.8% [95% CI 0.10, 0.53]) and median PFS (9.6 vs 5.7 months; HR 0.46, 95% CI 0.17, 1.21) was numerically longer in TROP2 QCS-NMR+ vs TROP2 QCS-NMR − tumors.
Conclusions
In this exploratory analysis, a trend toward increased ORR and longer PFS was observed in Chinese pts with TROP2 QCS-NMR+ tumors who received Dato-DXd. Although the number of pts was small, these results are consistent with TROP2 QCS-NMR+ data reported for TROPION-Lung01 and further demonstrate the potential of TROP2 QCS-NMR as a predictive biomarker for Dato-DXd in a/mNSCLC.
Clinical trial identification
NCT05460273.
Editorial acknowledgement
Medical writing support for the development of this abstract, under the direction of the authors, was provided by Mark Holland, PhD, of Ashfield MedComms, an Inizio Company, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca.
Funding
This trial is sponsored by AstraZeneca. In July 2020, Daiichi Sankyo entered into a global development and commercialisation collaboration with AstraZeneca for datopotamab deruxtecan (Dato-DXd).
Disclosure
Y. Wu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, BeiGene Beijing, Boehringer Ingelheim, Bristol Myers Squibb/China, Hengrui Pharmaceutical, MSD Oncology, Pfizer, Roche; Financial Interests, Personal, Advisory Role, Consulting: AstraZeneca, Boehringer Ingelheim, Roche, Takeda; Financial Interests, Institutional, Funding, Research funding: Bristol Myers Squibb, Boehringer Ingelheim, Pfizer, Roche. Y. Chen: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. M. Lu, B. Zhang, D. Carroll, J. Harper, D. Vonficht, H. Hu: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. All other authors have declared no conflicts of interest.