European Lung Cancer Congress (ELCC) 2025 Recap: Advances in Lung Cancer Research and Treatment

The European Lung Cancer Congress (ELCC) 2025, which took place in Paris from March 26-29, 2025, brought together lung cancer experts who presented the most anticipated clinical results. The three days served as an essential platform for exchanging valuable insights and fostering connections within the lung cancer community.

Lung cancer is one of the most common cancers and the leading cause of cancer deaths worldwide. There are mainly two types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC is the most common type of lung cancer, accounting for approximately 85% of all lung cancers. According to DelveInsight’s estimates, there were around 538,000 incident cases in 2024 in the seven major markets [the US, EU4 (Germany, France, Italy, Spain), the UK, and Japan]. The existing NSCLC treatment is mainly dominated by checkpoint inhibitors such as KEYTRUDA (pembrolizumab) and OPDIVO (nivolumab). As far as the EGFR-positive NSCLC market size is concerned, third-generation EGFRs such as AstraZeneca’s TAGRISSO (osimertinib are key therapies which is expected to dominate the market for the coming years. 

NSCLC is increasingly becoming a biomarker-driven market. EGFR is one of the profitable biomarker segments, with blockbuster NSCLC therapies such as TAGRISSO. Several key data readouts for the EGFR NSCLC segment took place at the 2025 ELCC conference. 

TAGRISSO is now the dominant EGFR inhibitor, generating a sales revenue of nearly USD 6.6 billion annually. Last year, TAGRISSO bagged one more FDA approval. On September 25, 2024, the US FDA approved TAGRISSO for adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations. Primary analysis of the phase III LAURA study in unresectable stage III EGFRm NSCLC without progression during or after chemoradiotherapy showed significant PFS improvement with TAGRISSO vs placebo (Median PFS: 39.1 vs 5.6 months and interim OS at 20% maturity). During the 2025 ELCC conference, AstraZeneca reported updated OS data, data on subsequent treatments, and postprogression outcomes from the Phase III LAURA study (NCT03521153). In this updated analysis, there was a continued trend toward OS benefit with TAGRISSO, with a median OS of 58.8 months versus 54.0 months for placebo. It is important to highlight that OS benefit was observed despite a high proportion of third-generation EGFR-TKI treatment after study treatment discontinuation in the placebo arm (80%). In addition to this, postprogression outcomes showed clinically meaningful improvement. Updated long-term findings from the LAURA study underscore TAGRISSO as a new SoC for unresectable stage III EGFR+ NSCLC after definitive chemoradiotherapy. Owing to the challenges and competition from Johnson & Johnson’s RYBREVANT (amivantamab) plus Yuhan Corporation’s LAZCLUZE (lazertinib) combo in the first-line setting, this is a move in the right direction for TAGRISSO. 

Owing to the success of TAGRISSO, several companies wanted to grab opportunities in the EGFR-NSCLC segment. With this, the EGFR NSCLC treatment landscape is extremely competitive. Besides TAGRISSO, AstraZeneca, in partnership with Daiichi Sankyo looking for the market opportunity for TROP2-directed DXd antibody drug conjugate (ADC) DATROWAY (datopotamab deruxtecan) in EGFR-mutated NSCLC. On January 13, 2025, DATROWAY was accepted and granted Priority Review in the US for EGFR-mutated NSCLC patients. The application was based on pooled analysis of the TROPION-Lung05 phase II study and supported by data from the TROPION-Lung01 phase III and TROPION-PanTumor01 phase I studies.  The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for its regulatory decision, is July 12, 2025. 

Just when AstraZeneca and Daiichi Sankyo were waiting for the FDA approval for DATROWAY, the company rolled out early data from the phase II ORCHARD platform study (NCT03944772), combining DATROWAY with blockbuster TAGRISSO. This platform study aims to identify novel combinations in the post-TAGRISSO setting. Apart from this, AstraZeneca also presented data from the Phase II SAVANNAH study (NCT03778229) where Savolitinib (ORPATHYS;  HUTCHMED) in combination with TAGRISSO for advanced EGFRm NSCLC with MET amplification or overexpression after progression on TAGRISSO). Current analysis of the phase II SAVANNAH trial reported 56% ORR by investigator assessment and 55% by blinded central review (BICR). Investigator assessment and BICR mDoR were 7.1 and 9.9 months, respectively. Additionally, median PFS was 7.5 and 7.4 months, respectively, for investigator assessment and BICR. The ongoing phase III SAFFRON study (NCT05261399) will investigate this combination against chemotherapy. 

TAGRISSO’s monopoly is under threat since the approval of  Johnson & Johnson’s RYBREVANT plus Yuhan Corporation’s LAZCLUZE in the first-line setting, RYBREVANT plus LAZCLUZE was approved by the US FDA in August 2024 for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations. RYBREVANT is an EGFR– and MET-directed bispecific antibody, and LAZCLUZE is a highly selective, brain-penetrant, third-generation oral EGFR TKI. 

First-line therapy landscape for EGFR-mutant NSCLC has changed over the years as a result of the FLAURA study, which established TAGRISSO as superior to first-generation TKI, the FLAURA2 study, which demonstrated TAGRISSO’s additional benefit with chemotherapy, and the MARIPOSA study, which showcased that RYBREVANT/LAZCLUZE combo as another first-line alternative. 

Recently, the MARIPOSA study has been the talk of the town. Johnson & Johnson reported the protocol-specified final OS analysis of the MARIPOSA study at ELCC 2025. Data suggests that this combo led to a statistically significant and clinically meaningful reduction in mortality compared to TAGRISSO in participants with previously untreated EGFR-mutant advanced NSCLC. In addition to this, participants with a history of their cancer spreading to their brain were less likely to have their disease grow further in their brain or die [intracranially progression-free at 3-year (36% vs. 18%) with a longer intracranial DoR when compared to TAGRISSO].  The biggest challenge of RYBREVANT has been its toxicity. The degree of benefit of OS cannot be translated if the high discontinuation rate remains high and without supportive measures. Even after the fact that patients using the RYBREVANT/LAZCLUZE combo live longer, some physicians may prefer TAGRISSO over this combo, owing to its safety concerns.

Expert Opinion: “It is important to say that the combination with amivantamab is quite toxic. There is a high degree of discontinuation of the drug. It requires very active prophylaxis with antibiotics and active help of the patients because they may develop severe skin toxicity and paronychia,” – MD, professor of medicine at the University of Chicago Medicine

In addition to the EGFR-NSCLC space, ELCC 2025 saw some significant advancements in KRAS-NSCLC. The KRAS-mutated NSCLC segment is becoming quite crowded, and it is anticipated that the treatment options for patients with KRAS G12C-mutated NSCLC may change in the near future. 

In Mirati Therapeutics’ KRYTSTAL-7 study, updated analysis showed PFS beyond 27 months for first-line KRAZATI (adagrasib; a KRAS inhibitor) plus KEYTRUDA combo in patients with KRAS G12C mutation and PD-L1 expression of at least 50%. However, the high levels of toxicity seen with the combination which means this combination will only be tolerated by the fittest patients. This suggests that balancing the benefit–risk profile of first-line combinations is still a challenge. 

GenFleet Therapeutics also presented the latest phase II data of the KROCUS study of their KRAS G12C inhibitor fulzerasib in combination with cetuximab (first-line), in a late-breaking abstract at the mini oral presentation. As per the analysis, DCR was 100%, ORR was 80%, with 58% of patients exhibiting ≥50% tumor shrinkage. KROCUS study also showed median PFS of 12.5 months, with median DOR not reached after a median follow-up of 12.8 months.

Encouraging and durable clinical activity was also reported for daraxonrasib (first-in-class pan RAS inhibitor), by Revolution Medicines, in patients with previously treated, locally advanced or metastatic RAS-mutant NSCLC. In Phase I/Ib, a multicentre open-label study, ORR was 38%, median DOR was 15.5 months, median PFS was 9.8 months, and median OS was 17.7 months.

New tyrosine kinase inhibitors (TKIs) in previously treated NSCLC with HER2-activating mutations showed impressive clinical activity, according to the data presented at the ELCC 2025 meeting. In NSCLC patients with HER2-activating mutations, Bayer’s BAY 2927088 showed encouraging findings. The median DOR was 8.7 months with a median follow-up of 17.2 months, and the ORR was 70.5% in patients who had advanced after at least one systemic therapy but were naïve to HER2-targeted therapy (cohort D). In patients who had previously received HER2-targeted ADCs (cohort E), over a median follow-up of 10.3 months, the ORR was 35.3% and the median DOR was 9.5 months. The most common treatment-related AE was diarrhea, although no patients discontinued due to this.

Merck‘s pivotal 3475A-D77 study data from their experimental subcutaneous KEYTRUDA with berahyaluronidase alfa were also presented at ELCC 2025. Merck’s KEYTRUDA is generally considered the ‘gold standard’ of care in 1L NSCLC when combined with platinum chemotherapy, regardless of PD-1 status. When compared to intravenous (IV) KEYTRUDA, the pharmacokinetics of this subcutaneous version are not inferior. Owing to the potential savings in pharmacy preparation, administration time, and infusion-related side effects, patients in the future are likely to prefer the SC option over IV administration. 

Expert Opinion: “These study findings demonstrate subcutaneous KEYTRUDA reduces time demands for both the patient and the healthcare provider, all while providing a consistent efficacy and safety profile with IV KEYTRUDA.” MD, PhD, head of Thoracic Tumors Group, Vall d’Hebron Institute of Oncology

Findings from the phase III KEYNOTE-799 trial (NCT03631784) were also presented at ELCC 2025, where investigators studied KEYTRUDA in combination with chemoradiotherapy in patients with stage III NSCLC. In two cohorts (including patients with squamous disease or nonsquamous cell histology), 4-year PFS rates were 39% to 46%, and matured 4-year OS data, between 40% and 55%. In addition to this, Golidocitinib, a JAK1 inhibitor from Dizal, showed potential in IO-resistant NSCLC when combined with anti-PD-1. 

SCLC accounts for approximately 15% of all lung cancer cases. The conference did not feature many trials related to SCLC, however, BioNTech’s Phase III with PD-L1 x VEGF bispecific antibody BNT327 caught the attention. It exceeded the target set by Roche’s PD-L1 blocker TECENTRIQ ([atezolizumab], the first FDA-approved treatment for first-line ES-SCLC in 20 years) plus chemotherapy in the Impower-133 trial. Toxicity looked potentially problematic, with 86% of patients experiencing a Grade 3 or higher treatment-related adverse event, compared with under 60% in Impower-133. However, the discontinuation rate with BNT327 plus chemotherapy was fairly low, at 6%, and there were no treatment-related deaths (although there were two deaths in the study, deemed unrelated). When compared with IMDELLTRA (a bispecific DLL3-directed CD3 T-cell engager representing a new immunotherapeutic approach), the latter drug has a black box warning for cytokine-release syndrome and neurotoxicity, so BioNTech might hope for a safety edge. 

The major trials discussed in the ELCC 2025 are in the table given below –