WCLC 2026: Next-generation modalities set to reshape the lung cancer landscape
The World Conference on Lung Cancer 2026 (WCLC 2026) took place from September 12–15, 2026, in Seoul, South Korea, hosted by the International Association for the Study of Lung Cancer (IASLC). During the conference, several important data presentations highlighted continued progress in both non-small cell (NSCLC) and small-cell lung cancer (SCLC), with data for aPD-1xVEGF bispecifics and B7-H3 antibody drug conjugates taking centre stage. See below for insights from the Lifescience Dynamics team on the key data and what it means for the lung cancer space:
NSCLC: One size may not fit all – ivonescimab shows signs of PD-L1 expression-dependant efficacy
Detailed longer follow-up data from the global Phase 3 HARMONi trial evaluating ivonescimab (PD-1xVEGF bsAb) + chemo vs. placebo + chemo in 2L+ EGFRm NSCLC builds on Summit’s July press release showing nominally significant overall mOS of 16.8 months vs. 14.0 months, HR 0.65 (0.61-0.95, nominal P=0.0151). Western patients saw a mOS of 17.5 months vs. 14.0 months, HR 0.76 (0.52-1.10) – the same HR as Asian patients (mOS 16.7 months vs. 14.0 months, HR 0.76 (0.58-0.99)). While geographical data appear consistent, 95% confidence intervals approaching (Asian) or exceeding 1 (Western) lowers overall confidence in the true efficacy of these patients. Furthermore, the lack of data presented on subsequent treatments following progression further limits the analysis.
Notably, patients in HARMONi were not selected for PD-L1 expression. While the “holy grail” would be for pan PD-L1 expression efficacy, it is a heavy bet that the VEGF-targeting component would offset the known PD-L1 expression dependency observed with PD-1 mAbs. As pointed out by Dr Brandao in her discussant presentation, although underpowered, subgroup analysis of PD-L1 expression for HARMONi suggests that PD-L1 ≥50% were the drivers of the observed benefit.
Similarly, with the Phase 3 China-only HARMONi-2 evaluating ivonescimab monotherapy in 2L+ non-AGA NSCLC, PD-L1 ≥50% expressors saw both better mOS (NR, HR 0.58 vs. 28.5 months, HR 0.85) and 36-month OS rates (53.4% vs. 38.6%) vs. PD-L1 1-49% expressors. A split was also observed between squamous and non-squamous (mOS: HR 0.65 vs. HR 0.79) patients, underpinning a growing sentiment reflected throughout the conference that with the variety of molecular differentiation on display between PD-(L)1xVEGF bsAbs in development, one size may not fit all.
SCLC: Tarlatamab innovates to improve convenience while B7-H3 ADCs come into view
At WCLC 2026, Amgen was focused on making tarlatamab (DLL3 T-cell engager) easier to deliver to patients with SCLC following its breakthrough approval in the US in May 2024 and Europe in March 2026. In the DeLLphi-309 trial, dosing tarlatamab every three- or four-weeks showed comparable exposure and survival to the approved two-week regimen. While currently administered as an intravenous infusion, the first data for a subcutaneous injection of tarlatamab from the DeLLphi-308 study were also encouraging, with a 30% response rate and, critically, lower rate of key adverse events including cytokine release syndrome and neurologic toxicities. Together with the positive DeLLphi-305 results toplined ahead of the conference, Amgen’s broad tarlatamab program is exploring improving convenience simultaneously to advancing into earlier treatment lines.
Elsewhere at WCLC 2026, a new drug class produced compelling in two large, randomized studies conducted in China. The B7-H3 targeting antibody drug conjugate (ADC) ris-rez achieved a median overall survival of 18.5 months vs. 10.3 months for single-agent chemotherapy (topotecan) in the ARTEMIS-008 study. Another B7-H3 ADC, tam-peli, achieved a medial overall survival of 13.3 months vs. 9.4 months in its study. With both B7-H3 ADCs reducing the risk of death by 54%, these Phase 3 studies, although restricted to China, are the first to validate early-data for B7-H3 ADCs, and other ADCS more broadly, suggesting this class of molecular-targeted chemotherapy could become an important weapon against the aggressive nature of relapsed SCLC. Global translatability and the efficacy of these drugs after tarlatamab are now among the key outstanding questions.
Looking ahead: ESMO 2026 & beyond
Next month in Madrid at the European Society for Medical Oncology Congress (ESMO 2026), the lung cancer community is set for another round of exciting updates as NSCLC and SCLC treatment paradigms continue to evolve. In NSCLC, initial pumitamig data from the Phase 2 ROSETTA Lung-107 data will be presented alongside sac-TMT OptiTROP-Lung04 and OptiTROP-Lung06 data and sigvotatug vedotin (BE6A LUNG-01). While in SCLC, data from the pivotal DeLLphi-305 study, set to be presented in a prestigious presidential session, is widely expected to establish tarlatamab as new standard-of-care in earlier treatment lines.
Looking into 2027, lung cancer remains set to continue as one of the most dynamic therapeutic areas as next-generation modalities move from early promise toward broader global validation. In NSCLC, attention will increasingly turn to whether PD-(L)1xVEGF bispecifics can reproduce China-led efficacy signals across global populations and identify the patients most likely to benefit, while in SCLC, tarlatamab’s expansion into earlier lines alongside the emergence of B7-H3 and DLL3 ADCs is likely to shift the focus toward treatment sequencing and novel combination strategies.
