WCLC 2026: The lung cancer drug development readouts that caught our eye

WCLC 2026: The lung cancer drug development readouts that caught our eye By Jules Adam Add Labiotech as your Google Preferred Source 10 minutesmins September 18, 2026 10 minutesmins Share WhatsApp Twitter Linkedin Email Photo credits: Aakash Dhage Add Labiotech as your Google Preferred Source Newsletter Signup - Under Article / In Page"*" indicates required fieldsCommentsThis field is for validation purposes and should be left unchanged.Subscribe to our newsletter to get the latest biotech news!By clicking this I agree to receive Labiotech's newsletter and understand that my personal data will be processed according to the Privacy Policy.*Company name*Job title*Business email* The World Conference on Lung Cancer (WCLC) 2026 took place in Seoul from September 12 to 15, bringing new clinical trial results in lung cancer. Several late-stage readouts stood out this year, including new approaches to long-standing drug targets, treatments moving into earlier lines of therapy and a few reminders that promising combinations can’t always translate into better outcomes. Here are the drug development results that caught our attention. Table of contentsTwo B7-H3 ADCs originating from China delivered phase 3 wins in small-cell lung cancer Two different antibody-drug conjugates (ADCs) targeting the same protein produced remarkably similar phase 3 results in relapsed small-cell lung cancer (SCLC) at WCLC 2026. Hansoh Pharma’s risvutatug rezetecan (Ris-Rez) and MediLink Therapeutics’ tambotatug pelitecan (Tam-Peli) both reduced the risk of death by 54% compared with topotecan, an established chemotherapy option. Both drugs target B7-H3, a protein found at high levels in many tumors, including SCLC, but with more limited expression in healthy tissues. This makes B7-H3 an attractive delivery target, although early studies suggest that the amount of B7-H3 expressed by a tumor does not necessarily predict whether a patient will respond to these ADCs. In the 461-patient ARTEMIS-008 trial, Ris-Rez extended median overall survival to 18.5 months from 10.3 months with topotecan, while progression-free survival increased from 3.0 to 7.2 months. The response rate was 58.3% versus 12.6%. The 451-patient TAISHAN-302 trial produced a similar result with Tam-Peli extending overall survival to 13.3 months from 9.4 months and progression-free survival to 7.4 months from 2.8 months, with response rates of 59.1% and 9.7%, respectively. Severe treatment-related adverse events were also less frequent with both ADCs compared to topotecan. The similarities don’t end there as both drugs also originated in Chinese biotechs before attracting large pharmaceutical partners. GSK licensed Ris-Rez from Hansoh in 2023 for $185 million upfront and up to $1.525 billion in milestones, while Roche licensed rights to MediLink’s Tam-Peli, paying $570 million upfront. GSK is now testing Ris-Rez in a global phase 3 trial, while Roche plans its own global phase 3 development of Tam-Peli. Meanwhile, BioNTech and DualityBio are already exploring where B7-H3 ADCs could go next. At WCLC, their B7-H3 ADC elfetabart drozuntecan combined with the PD-L1×VEGF-A bispecific pumitamig produced a 70.4% response rate in 71 SCLC patients in an early phase 1b/2 study. The evidence is much earlier, but B7-H3 ADC development is already expanding beyond standalone treatment. Ivonescimab strengthens the case for PD-1/VEGF bispecifics Akeso’s ivonescimab became the first PD-1/VEGF bispecific antibody to show an overall survival advantage over pembrolizumab in a phase 3 trial. At WCLC 2026, updated results from HARMONi-2 showed that patients with PD-L1-positive advanced non-small cell lung cancer (NSCLC) lived a median of 30.8 months with ivonescimab compared with 22.6 months with Keytruda, reducing the risk of death by 27%. Suggested Articles ESC 2026: The drug development readouts that stood out NLS Days 2026: what’s dealmaking like in the Nordics? Bladder cancer treatment: where are we standing in 2026? Seven lung cancer companies advancing new treatments in 2025 Ivonescimab combines two established cancer treatment strategies. Blocking PD-1 removes a brake that tumors use to suppress immune cells, while blocking VEGF limits the formation of blood vessels that support tumor growth and can also make the tumor environment less immunosuppressive. Ivonescimab is designed to bind more strongly when both PD-1 and VEGF are present, potentially concentrating its activity in the tumor microenvironment. HARMONi-2 had already shown that this approach could delay disease progression. In the trial, first-line ivonescimab previously extended median progression-free survival to 11.1 months from 5.8 months with pembrolizumab. The WCLC readout addressed whether that advantage would translate into longer survival. The benefit was particularly pronounced among patients whose tumors expressed PD-L1 at 50% or higher, where ivonescimab reduced the risk of death by 42%. Serious treatment-related adverse events occurred in 29.9% of patients receiving ivonescimab and 21.6% receiving pembrolizumab. This is evidence that simultaneously targeting PD-1 and VEGF can improve on checkpoint inhibition alone, although whether ivonescimab can reproduce its advantage over pembrolizumab in broader patient populations remains to be seen, as HARMONi-2 enrolled patients only in China. Ivonescimab’s separate global phase 3 HARMONi trial is testing the drug in a different setting, combined with chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated NSCLC whose disease progressed after targeted treatment. Updated WCLC results showed a 24% reduction in the risk of death globally, with the same hazard ratio of 0.76 in the Western subgroup. In the bigger picture, Ivonescimab is no longer alone in the PD-1/VEGF bispecific field. In January, AbbVie paid RemeGen $650 million upfront for rights outside China to RC148, now ABBV-1480. At WCLC 2026, the drug combined with chemotherapy produced response rates of 90% in 30 patients with squamous NSCLC and 75.9% in 29 patients with non-squamous disease at the dose selected for further development. The cohorts are still small, but a global phase 3 trial is now underway, adding another Chinese-origin drug to the emerging PD-1/VEGF class. Enhertu moves HER2-mutant NSCLC into the first line AstraZeneca’s Enhertu is already an established treatment for previously treated HER2-mutant NSCLC. At WCLC 2026, AstraZeneca presented its phase 3 trial to find out whether the HER2-targeted ADC should be used from the start, ahead of the current first-line combination of pembrolizumab and chemotherapy. Enhertu extended median progression-free survival to 14.3 months from 8.3 months with pembrolizumab plus chemotherapy, reducing the risk of progression or death by 37%. The response rate was also higher, at 70% compared with 44.5%, while responses lasted a median of 13.4 months versus 9.7 months. The overall survival data are less clear. Patients lived a median of 29.3 months with Enhertu and 33.1 months with chemo-immunotherapy, although the data are still immature and nearly half of those who started with chemo-immunotherapy later received a HER2-targeted treatment. This may have narrowed the survival difference between the two groups, and longer follow-up will be needed to determine whether starting with Enhertu ultimately helps patients live longer. Safety also remains part of that trade-off. Interstitial lung disease (ILD) or pneumonitis, a known risk with Enhertu, occurred in 20.8% of patients. Most cases were mild or moderate, but four patients (1.8%) died from ILD. Once again, longer follow-up will be needed to see whether the clear first-line advantage in disease control eventually translates into an overall survival benefit. Zipalertinib adds an oral option to the EGFR exon 20 race EGFR-targeted therapies are already important in some forms of NSCLC, but tumors carrying EGFR exon 20 insertions have proved much harder to treat with conventional tyrosine kinase inhibitors (TKIs). These mutations alter the receptor in a way that makes many existing TKIs less effective, while increasing the dose can also inhibit normal EGFR and cause toxicity. Zipalertinib is an oral TKI designed to inhibit exon 20-mutant EGFR while limiting activity against normal EGFR. At WCLC 2026, the phase 3 REZILIENT3 trial tested zipalertinib plus chemotherapy as a first-line treatment in just under 300 patients with advanced EGFR exon 20 insertion-positive NSCLC. The combination extended median progression-free survival to 14.5 months from 8.5 months with chemotherapy alone, reducing the risk of progression or death by 50%. The response rate was also higher, at 65% compared with 40.3%, and responses lasted a median of 14.2 months versus 9.9 months. Overall survival data are not yet mature. However, the efficacy improvement came with additional toxicity. Grade 3 or higher adverse events occurred in 87.1% of patients receiving zipalertinib plus chemotherapy compared with 54.4% with chemotherapy alone, although much of the difference came from blood-related side effects. Severe anemia occurred in 48.6% versus 12.5% of patients, thrombocytopenia in 30% versus 8.1%, and neutropenia in 33.6% versus 22.1%. These side effects were concentrated mainly during the first chemotherapy cycles and became less frequent after. Zipalertinib would enter a field where targeted first-line treatment is already available. Amivantamab, an EGFR×MET bispecific antibody, is approved in combination with chemotherapy. Results presented at WCLC showed median overall survival of 34.3 months with amivantamab plus chemotherapy versus 27.9 months with chemotherapy alone. The difference did not reach statistical significance, although 76% of eligible patients in the chemotherapy group received amivantamab after their disease progressed, potentially narrowing the difference between the groups. The two drugs have not been compared directly, but zipalertinib potentially adds an oral TKI to an exon 20 treatment landscape currently led by an antibody-based regimen. If approved, questions around efficacy, toxicity, convenience and eventually how the treatments should be sequenced will become central. Trodelvy fails to improve on pembrolizumab Adding Gilead’s Trodelvy to pembrolizumab failed to significantly improve outcomes in first-line metastatic NSCLC providing a counterpoint to some of the more successful ADC results presented at WCLC. The phase 3 trial enrolled 620 patients whose tumors expressed high levels of PD-L1, a group for whom pembrolizumab alone is an established treatment option. Trodelvy is an ADC targeting Trop-2, a protein expressed in lung cancer, and was tested with pembrolizumab in the hope that directly killing tumor cells could improve on checkpoint inhibition alone. The combination did appear to delay progression for longer with median progression-free survival of 11.8 months with Trodelvy plus pembrolizumab compared with 7.7 months with pembrolizumab alone, while response rates were 55.6% and 43.7%, respectively. However, the reduction in the risk of progression or death was more modest, at 19%, and the result did not meet the trial’s prespecified threshold for statistical significance. Overall survival provided no indication of an advantage either: at the interim analysis, patients lived a median of 21.5 months with the combination and 22.8 months with pembrolizumab alone. Adding Trodelvy also substantially increased toxicity, with severe treatment-related adverse events in 55.7% of patients compared with 16.5% on pembrolizumab alone. What comes next after WCLC 2026? WCLC 2026 showed lung cancer drug development increasingly building on treatments that already work. Several of the biggest readouts involved moving targeted drugs into earlier treatment, combining mechanisms in a single drug or finding new ways to attack established targets. At the same time, the failure of Trodelvy to improve on pembrolizumab added contrast around that strategy. Earlier in the pipeline, BlossomHill Therapeutics’ BH-30643 is designed to overcome EGFR resistance mutations that emerge after existing TKIs and produced responses in 45% of 40 patients with C797S-positive disease in the phase 1/2 SOLARA trial. Meanwhile, the EGFR×HER3 bispecific ADC izalontamab brenitecan produced a 33.3% response rate at the dose now moving into phase 3 in previously treated EGFR-mutant NSCLC. Both remain early studies, but they represent another generation of drugs already being developed around the resistance mechanisms left behind by current therapies. 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