🧬 A bispecific hitting DLL4 + VEGF-A can clearly move response and PFS — but the toxicity trade-off matters.
@OncoAlert @myESMO
At #ESMO26, a randomized phase 2/3 trial tested tovecimig + paclitaxel versus paclitaxel alone in previously treated advanced biliary tract cancer.
📊 n=168
➡️ ORR: 17.1% vs 5.3%
p=0.031
➡️ Median PFS: 4.7 vs 2.6 months
HR 0.44, p<0.0001
➡️ OS: HR 1.05
Interpretation limited by 54% crossover
But the safety signal deserves attention:
⚠️ Grade ≥3 hypertension: 44%
⚠️ Treatment discontinuation due to TEAEs: 40% vs 15%
🎯 Why this matters: the efficacy signal is real, especially for PFS, but in a heavily pretreated population the clinical value will depend on whether we can identify patients who gain enough benefit to justify the added toxicity.
For me, the next question is whether DLL4/VEGF biology can become a true selection strategy, rather than another broadly applied antiangiogenic approach.
Important data from @DrElkhoueiry @JavleMilind and collaborators.
Pinging @CathyEngMD @BenWestphalen @graokane @NiuSanford @GillSharlene @pashtoonkasi @DrVilmaPBarcia @GIMedOnc @DaisukeKotani @KoheiShitara
#OncoAlert #ESMO26 #BiliaryTractCancer #GIOncology #Bispecifics #PrecisionOncology
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https://esmocongress.esmo.orgOncoAlert 4Sight Abstracts to be Presented at #ESMO26 A Randomized Trial of Paclitaxel ± Tovecimig in Previously Treated Patients With Advanced Biliary Tract Cancer @DrElkhoueiry @JavleMilind 🔬 Randomized phase 2/3 (n=168, 2:1): tovecimig (DLL4 × VEGF-A bispecific) + paclitaxel vs paclitaxel in previously treated advanced BTC. Primary endpoint: BICR ORR. ➡️ ORR 17.1% vs 5.3% (p=0.031); median PFS 4.7 vs 2.6 mo, HR 0.44 (p<0.0001) ➡️ OS HR 1.05 (p=0.78); 54% crossed over to tovecimig + paclitaxel ➡️ Related grade ≥3 hypertension 44%; TEAEs leading to discontinuation 40% vs 15% ✅ Significant ORR and PFS advantage; OS analysis confounded by high crossover, precluding a meaningful comparison. 🎙️ Nilofer Azad 👥 Zishuo Hu · Ilyas Sahin · Renuka Iyer · Olivia Aranha · Howard Hochster · Priyadarshini Pathak · Scott Paulson · Aparna Kalyan · Chih-Yi Liao · Nguyen Tran · Robin Kelley · Gregory Heestand · David Cosgrove · Anthony El-Khoueiry · Mitesh Borad · Nashat Gabrail · Umair Majeed · Lingling Du · Suneel Kamath · Nathan Shumway · Rachna Shroff · Lipika Goyal · Minori Rosales · Milind Javle (4Sight Made from Abstracts publicly available at the ESMO website) @CathyEngMD, @BenWestphalen, @graokane, @NiuSanford, , @GillSharlene, @pashtoonkasi, @DrVilmaPBarcia, @Erman_Akkus, @GIMedOnc, @UOzkerim, @MarioBalsaMD, @p_ciracimd, @DraMartinezLago, @DaisukeKotani, @Aiims1742, @ARosen380, @realbowtiedoc, @KoheiShitara,在 X 查看被引用的帖子
来源：Dra. María Natalia Gandur Quiroga · x.com