来自湖畔的现场报道：美国临床肿瘤学会（ASCO）周日最佳动态（阿斯利康、拜耳、Genmab、葛兰素史克、默克集团）

Restricted - External European Pharmaceuticals & Life SciencesNEUTRALEuropean Pharmaceuticals & LifeSciencesEmily Field, CFA+44 (0)20 7773 6263emily.field@barclays.comBarclays, UKShirley Chen, PhD+44 (0)20 7773 2109shirley.chen@barclays.comBarclays, UKCharles Pitman-King, CFA+44 (0)20 3134 6023charles.pitman-king@barclays.comBarclays, UKYihan Li, PhD+44 (0)20 3555 3563yihan.li@barclays.comBarclays, UKSidhartha Modi+91 (0)22 6175 1326sidhartha.modi@barclays.comBarclays, UKAnurag Surendra Sharma+91 (0)22 6175 4548anuragsu.sharma@barclays.comBarclays, UK Lung Cancer—Non-Small Cell Metastatic: Oral Abstract Session. . . . . . . 3Hematologic Malignancies—Plasma Cell Dyscrasia - Poster Session. . . 6Hematologic Malignancies—Lymphoma and Chronic LymphocyticLeukemia - Poster Session. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8Gynecological Cancers - Poster Session . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Sarcoma - Oral Abstract Session. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 a Proportion of pts with confirmed CR + PR + SD at 12 wks. b.c Median (95% CI) PFS follow-up, mo: b17.3 (11.3−26.8); c23.5 (17.3−27.9)Lung Cancer—Non-Small Cell Metastatic: OralAbstract Session8501: TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) pluspembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer(aNSCLC).Background:TROPION-Lung02 (NCT04526691) evaluated the TROP2-directed antibody-drugconjugate (ADC) Dato-DXd plus pembro combination with or without Pt-CT in aNSCLC. Here wereport primary analyses of pts receiving combination therapy in the 1L setting.Methods:Pts across 6 cohorts were dosed with Dato-DXd (4 or 6 mg/kg) plus pembro 200 mgalone (doublet) or with pembro plus Pt-CT (triplet; cisplatin 75 mg/m2or carboplatin AUC 5)Q3W. PD-L1 expression (tumor proportion score) was assessed locally byimmunohistochemistry (22C3 assay). Primary objectives were safety and tolerability;efficacywas a secondary objective.Results:As of Apr 29, 2024, 96 pts received either the doublet (n=42) or triplet (n=54)combination as 1L therapy; 29% and 15% of pts were ongoing, respectively. Median ages were65 (doublet) and 64 years (triplet). Median treatment durations were 9.7 and 5.8 months,respectively. Stomatitis (doublet, 57%; triplet, 33%) and nausea (doublet, 42%; triplet, 48%),primarily Gr 1–2, were the most common adverse events (AEs) across both regimens. Treatmentrelated serious AEs occurred in 5 (12%) and 12 (22%) pts in each cohort and no deaths related tostudy drug were seen.Efficacyoutcomes, including by histology, are summarized in the Table.Biomarker analyses, includingefficacyby PD-L1 status, will be presented.Conclusions:In this largest data set to date evaluating an ADC combined with an anti-PD-1/L1agent in the 1L setting, the combination of Dato-DXd plus pembro treatment both with andwithout Pt-CT elicited durable antitumor activity in pts with aNSCLC. Tolerability of thecombinations was as expected, based on known profiles of the individual agents.Discussion: Right out of the Gate: New Directions in Front-Line Therapy inMetastatic Non–Small Cell Lung Cancer•How can we personalize therapies in 1L for pts with NSCLC w/o AGAs? KN-024 has wellestablished 5 year survival data but OS rates remain ¬30%. 3 FIGURE 1. TL-02 resultsSource: ASCO, Barclays Research2 June 2025 •1L adagrasib + pembro in pts with KRASG12Cm NSCLC. ORR was 44% highlighting 61% in PD-L1 => 50%. PFS was 27.7m in this group and mOS not reached. There were high rates of doseinterruption and reduction; discontinuation rates were in-line with other studies. PromisingPFS and OS in PD-L1 high. While not practice changing, does appear promising for high PD-L1patients. KROCUS study combining with cetuximab and SCARLET combining with platinum/pemetrexed could be interesting.•TROPION-Lung02: High rates of discontinuation noted, 1/3 discontinued any drug and 1/3discontinued Dato-DXd. Promising mDOR compares favourably to KN-189. Strengths includeTROP2 NMR and relatively long follow up. Limitations include non-randomized and includingof SQ histology. Doublet does appear promising for pts with QCS NMR+. Triplet does notappear toofferadvantages over the doublet.Q&A•QCS NMR only takes two slides, but there is tissue exhaustion in clinical trials. As biomarkersare refined, hopefully they will use less and less tissue.•Biomarker questions: We now have two datasets showing that the biomarker in 2L ispredictive of outcomes and in 1L is correlative. This biomarker ‘shakes out.’ Scalability will bepredicated on using the biomarker. Will the compound depend on the biomarker? We need tosee more data.•Triplet: Very small numbers and 20% had brain mets (which is double of what is normallyseen in 1L). The triplet had 60% 6mg/kg vs. 90% in the doublet arm (RP3D). The doublet islikely more reflective of a ‘real world’ study.8504: SOHO