2025 World Conference on Lung Cancer (WCLC): key news stories
With the 2025 World Conference on Lung Cancer (WCLC, 6–9 September, Barcelona, Spain) wrapped up, we have collated key headlines for you in our handy news roundup. Read about breakthrough trials for small cell lung cancer (SCLC), advanced NSCLC and MTAP-deleted lung cancers.
First-in-human trial shows promising results for DLL3-targeted ADC in SCLC
A first-in-human Phase 1 study of a DLL3-directed antibody-drug conjugate, termed SHR-4849, has demonstrated early signs of anti-tumor activity in patients with relapsed small cell lung cancer.
The drug consists of a humanized anti-DLL3 IgG1 monoclonal antibody (DLL3 is highly expressed in small cell lung cancer) linked to a DNA topoisomerase I inhibitor.
The objective response rate among 42 evaluable SCLC patients was 59.5%, whilst the disease control rate was 90.5%. Objective response rate was 69.2% among patients with at least 12 weeks of follow-up, and 77.8% at the 2.4 mg/kg expansion dose. The treatment showed a manageable safety profile; common treatment-related adverse events included decreased white blood cell count, anemia, neutropenia and nausea. No of the treatment-related adverse events resulted in dose discontinuation or death.
Next steps include a dose expansion to determine the recommended Phase II dose as well as clinical development to assess SHR-4849’s potential as a therapeutic option for DLL3-expressing SCLC.
“These encouraging early data support further investigation of SHR-4849 as a potential treatment for patients with DLL3-positive relapsed SCLC,” stated study lead LinLin Wang (Affiliated Cancer Hospital of Shandong First Medical University, Jinan, China).
Unprecedented overall survival observed for tarlatamab with anti-PD-L1 for ES-SCLC
Data from the Phase 1b DeLLphi-303 trial showcased unprecedented overall survival results and an acceptable safety profile for tarlatamab in combination with anti-PD-L1 therapy as a first-line maintenance treatment for extensive stage (ES)-SCLC patients.
The DeLLphi-303 trial enrolled 88 patients with ES-SCLC who had completed 4–6 cycles of platinum-etoposide chemotherapy and anti-PD-L1 (unless unavailable) without disease progression. Within 8 weeks of the start of their last chemo-immunotherapy cycle, patients began maintenance treatment with tarlatamab in combination with either or durvalumab disease progression.
After a median follow-up of 18.4 months, the median overall survival was 25.3 months, and the median progression-free survival was 5.6 months.
An acceptable safety profile was observed, cytokine release syndrome occurred in 56% of patients (predominantly at Grade 1 severity), whilst 6% of patients experienced immune effector cell-associated neurotoxicity syndrome. Of note, treatment-emergent and treatment-related adverse events decreased over time, indicating long-term tolerability.
Experimental viral immunotherapy shows durable survival benefit for advanced NSCLC
A Phase 2a clinical trial has demonstrated encouraging long-term survival outcomes for CAN-2409, an experimental viral immunotherapy, in patients with advanced NSCLC who previously failed to respond adequately to immune checkpoint inhibitors (IC).
The study evaluated 46 eligible unresectable Stage III/IV NSCLC patients who received two intratumoral injections of CAN-2409 combined with oral valacyclovir, demonstrating a median overall survival of 24.5 months with 37% of patients surviving beyond 2 years. For patients with progressive disease at baseline, a median overall survival of 21.5 months was observed.
“Notably, patients with non-squamous histology demonstrated longer overall survival than those with squamous histology (25.4 vs. 13.3 months), linked to a significant increase in cytotoxic effector T cells and other favorable immunological changes following treatment,” explained Charu Aggarwal (Abramson Cancer Center at the University of Pennsylvania, PN, USA).
Throughout the extended follow-up period of 32.4 months, CAN-2409 maintained a favorable safety and tolerability profile.
“This extended follow-up confirms the durable survival benefit of CAN-2409 for patients who otherwise have limited treatment options after failing ICI therapy. These results strongly support advancing CAN-2409 into a larger, randomized controlled trial, particularly in patients with non-squamous histology,” concluded Aggarwal.
Durable responses for BMS-986504 in MTAP-deleted lung cancers
A Phase I trial revealed that BMS-986504, a first-in-class MTA-cooperative PRMT5 targeting agent, demonstrated significant antitumor activity in heavily pretreated MTAP-deleted NSCLC patients, including in EGFR and ALK-positive tumors.
The therapy achieved a 29% overall response rate and 80% disease control rate among 35 evaluable NSCLC patients.
Notably, the drug showed effectiveness in patients with EGFR and ALK alterations who had previously progressed on targeted therapies, with responses observed in 4 of 7 EGFR-positive and 2 of 4 ALK-positive patients. This represents a potential breakthrough for these difficult-to-treat molecular subgroups.
The treatment demonstrated a manageable safety profile with predominantly grade 1-2 adverse events. Overall, 14% of solid tumor patients experienced grade 3 or higher treatment-related adverse events.
For patients with advanced NSCLC with MTAP-deletions, there are two further studies underway, NCT06855771 and NCT07063745 underway.