“The 2025 ESMO Congress will feature multiple late-breaking abstracts that could reshape the lung cancer treatment landscape,” Amol Akhade, MD, MBBS, a senior consultant at Fortis Hospitals Mumbai, consultant medical oncologist at Suyog Cancer Clinics in Thane, and the honorary in-charge consultant medical oncologist at Topiwala National Medical College in Mumbai, India, said in an email to OncLive. “Among them, the [trials] that stand out as particularly important [are the phase 3] HARMONi-6 [NCT05840016] and OptiTROP-Lung04 [NCT05870319] trials, as well as the [the phase 1] Beamion LUNG-1 trial [NCT04886804] and [the phase 1/2] SOHO-01 trial [NCT05099172] in the HER2-mutant setting.”
To gain further insights on the most anticipated lung presentations at the upcoming congress, we also spoke with:
- Sagus Sampath, MD, a radiation oncologist at City of Hope in Duarte, California.
- Balazs Halmos, MD, a professor in the Department of Oncology (Medical Oncology) and Department of Medicine (Oncology and Hematology) and associate director of clinical science at Montefiore Einstein Comprehensive Cancer Center in the Bronx, New York.
- D. Ross Camidge, MD, PhD, a professor in medicine-medical oncology and director of the Thoracic Oncology Clinical and Clinical Research Programs at the University of Colorado Cancer Center/Anschutz Medical Campus in Aurora.
- Edward B. Garon, MD, MS, a thoracic medical oncologist and a professor of medicine at the David Geffen School of Medicine at UCLA in Los Angeles, California.
How Could Data From NorthStar Reshape the EGFR-Mutant Treatment Landscape?
LBA72 - NorthStar: a phase II randomized study of osimertinib (OSI) with or without local consolidative therapy (LCT) for metastatic EGFR-mutant non–small cell lung cancer (NSCLC)
Session time: Friday, 10/17, 16:00-16:10 CEST
Sampath: The No. 1 abstract that I'm looking forward to hearing more about is the [phase 2] NorthStar trial [NCT03410043]. It's a randomized trial looking at osimertinib [Tagrisso] alone vs osimertinib and [local consolidative therapy] in patients with oligometastatic disease. I believe [these data could be] practice-changing and provide even more support for this approach. At the same time, given that the science has changed with new trials in the upfront setting showing that patients may benefit more from multiagent therapy, we probably need to now start looking at another version of NorthStar [where], instead of just osimertinib alone, [we examine] either an osimertinib-chemotherapy regimen or an amivantamab-vmjw [Rybrevant]–lazertinib [Lazcluze] regimen.
Halmos: We have seen the early success of this strategy from studies in China. Will we see proof of concept now in the US? And will the benefit be larger than anticipated with the frontline space shifting, thanks to the overall survival [OS] benefits [observed in the phase 3] FLAURA2 [NCT04035486] and MARIPOSA [NCT04487080] trials?1,2
Camidge: Given the increased penetrance of ‘chemoconsolidation’ as a concept in FLAURA2, radiation consolidation without a pharma sponsor has lagged behind in evidence since the paper "Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non-Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study" from Daniel Gomez, MD, MBA. [It will be] nice to see the updates on this series of studies with different TKIs [tyrosine kinase inhibitors], including this one with osimertinib.
What Key Data Are Being Presented in SCLC?
2757O - Tarlatamab with first-line chemoimmunotherapy for extensive stage small cell lung cancer (ES-SCLC): DeLLphi-303 study
Session time: Saturday, 10/18, 8:30-8:40 CEST
Camidge: In SCLC, the challenges and the promise of DLL3 bispecific T-cell engagers make a move to the first line intriguing. When do you start it, and how feasible is this for patients who might be frail or far from hospitals for inpatient stays? There will be something very interesting in the details of the [phase 3] DeLLphi-303 study[NCT06211036].
Will New Data With TKIs Be Presented?
1987MO - Efficacy of lorlatinib after failure of a first-line ROS1 tyrosine kinase inhibitor (ROS1 TKI) in patients (pts) with advanced ROS1-positive non-small cell lung cancer (ROS1+ NSCLC) (IFCT-2003 ALBATROS)
Session time: Sunday, 10/19, 9:31-9:36 CEST
Camidge: The off-label use of lorlatinib [Lorbrena] for ROS1-[positive disease] is at last getting some data to present, but as prior ROS1 TKIs may have had poor central nervous system [CNS] penetration and lorlatinib has good CNS penetration but limited ROS1 mutation coverage, showing lorlatinib’s efficacy by prior drug, site of target lesions, and known ROS1 resistance mutation for extracranial disease will be needed to interpret this [data] properly.
LBA75 - Sevabertinib (BAY 2927088) in advanced HER2-mutant non-small cell lung cancer (NSCLC): Results from the SOHO-01 study
Session time: Friday, 10/17, 16:25-16:35 CEST
LBA74 - Zongertinib as first-line treatment in patients with advanced HER2-mutant NSCLC: Beamion LUNG 1
Session time: Friday, 10/17, 16:35-16:45 CEST
Halmos: [I am looking forward to] updated presentations on the leading ERBB2 TKI twins, zongertinib [Hernexeos] and sevabertinib, from the Beamion LUNG-1 and SOHO-01 studies. Suddenly, there is an embarrassment of riches with [zongertinib] already being FDA approved and [sevabertinib] likely soon to join.3 One might need a hawk’s eye to be able to differentiate between these agents, so let’s see if we get an extra sharp look at ESMO!
Akhade: HER2-mutant NSCLC will receive significant attention with Beamion LUNG-1 testing zongertinib in the first-line setting and SOHO-01 evaluating sevabertinib in previously treated patients. HER2-driven lung cancers are rare but aggressive, and fam-trastuzumab deruxtecan-nxki [T-DXd; Enhertu] has set a high bar. These next-generation TKIs will be scrutinized for efficacy, CNS penetration, and safety, as they could provide a more tolerable alternative or a complement to antibody-drug conjugates [ADCs].
What Other Agent Classes Will Have Updated Data?
LBA5 - Sacituzumab tirumotecan (sac-TMT) vs platinum-based chemotherapy in EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) following progression on EGFR-TKIs: results from the randomized, multi-center phase 3 OptiTROP-Lung04 study
Session time: Sunday, 10/19, 16:52-17:04 CEST
Akhade: OptiTROP-Lung04 brings forward sacituzumab tirumotecan, a novel TROP2-directed ADC, in patients with EGFR-mutant NSCLC who have progressed after EGFR TKI therapy. Treatment options for this population remain limited, and chemotherapy has long been the default. A positive randomized readout would firmly establish ADCs as the next line of therapy and potentially spare patients from conventional chemotherapy.
LBA4 - Phase III study of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small cell lung cancer (HARMONi-6)
Session time: Sunday, 10/19, 16:30-16:42 CEST
Akhade: HARMONi-6 is comparing ivonescimab—a PD-1/VEGF bispecific antibody—plus chemotherapy vs tislelizumab [Tevimbra] plus chemotherapy in the frontline setting for squamous NSCLC. This is the first head-to-head trial of a bispecific strategy vs a PD-1 inhibitor, and it directly challenges the current immunotherapy backbone. If progression-free survival [PFS] and overall survival [OS] benefits are confirmed with manageable toxicity, HARMONi-6 could redefine standards in squamous NSCLC.
Garon: There has been a lot of excitement regarding ivonescimab, but to date, it has been easier for the agent to demonstrate a PFS benefit than an OS benefit. An OS benefit in a trial such as this would be meaningful for the interpretation of this mechanism.
Halmos: Who does not enjoy a new sequel to the ivonescimab family drama with the ups and downs between news releases and conference presentations yielding a thrilling but so far inconclusive roller coaster ride as to the overarching question [of whether] PD-(L)1/VEGF bispecifics truly outperform checkpoint inhibitors. At ESMO, we will see the results of the HARMONi-6 randomized study comparing chemotherapy plus ivonescimab vs chemotherapy plus the anti–PD-1 agent, tislelizumab.
Akhade: Together, these trials highlight the momentum in lung cancer research—moving beyond broad immunotherapy and into targeted and mechanism-driven approaches. The results presented at the 2025 ESMO Congress will be crucial in shaping the next wave of standards in thoracic oncology.
References
- Planchard D, Jänne PA, Cheng Y, et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi:10.1056/NEJMoa2306434
- Yang JCH, Lu S, Hayashi H, et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. Published online September 7, 2025. doi:10.1056/NEJMoa2503001
- FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. FDA. August 8, 2025. Accessed October 1, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zongertinib-non-squamous-nsclc-her2-tkd-activating-mutations
