As the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting approaches, lung cancer specialists are highlighting several groundbreaking studies that could reshape treatment paradigms across both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).
Tarlatamab Shows Survival Advantage in Relapsed SCLC
The phase 3 DeLLphi-304 trial (Abstract LBA8008) comparing tarlatamab-dlle (Imdelltra) to standard chemotherapy in second-line small cell lung cancer has emerged as one of the most anticipated presentations at ASCO 2025. According to a recent press release, tarlatamab demonstrated superior overall survival compared to chemotherapy in patients with relapsed SCLC.
"This abstract is one of the most promising studies for me this year," said Dr. Parth A. Desai from Fox Chase Cancer Center. "Given the almost universal relapse rates and high mortality in SCLC, these results could be transformative."
The DeLLphi-304 study builds on tarlatamab's accelerated FDA approval in May 2024, which was granted based on the phase 2 DeLLphi-301 trial results published in the New England Journal of Medicine. If the final data validate the initial findings, tarlatamab may establish itself as the new standard second-line therapy for SCLC.
Dr. Angel Qin from the University of Michigan Health's Rogel Cancer Center emphasized, "Depending on the results, it can really change the SCLC treatment landscape."
Lurbinectedin Plus Atezolizumab Shows Promise in First-Line Maintenance
Another significant advancement in SCLC management comes from the phase 3 IMforte trial (Abstract 8006), which evaluated lurbinectedin (Zepzelca) plus atezolizumab (Tecentriq) as maintenance therapy following induction chemoimmunotherapy in extensive-stage SCLC.
Jazz Pharmaceuticals reported that this combination demonstrated a statistically significant improvement in overall survival compared with atezolizumab monotherapy. Lurbinectedin, a DNA-damaging chemotherapy agent, received FDA approval in June 2020 for relapsed SCLC.
"If the IMforte trial confirms the survival benefit, it would bring lurbinectedin up the ladder as a maintenance strategy addition to immunotherapy alone—the current standard—in the extensive stage SCLC treatment landscape," Dr. Desai explained.
Neoadjuvant Nivolumab Plus Chemotherapy in Resectable NSCLC
The CheckMate 816 trial (Abstract LBA8000) will present overall survival data for neoadjuvant nivolumab (Opdivo) plus chemotherapy in patients with resectable NSCLC. According to a press release from Bristol Myers Squibb in February 2025, this regimen led to statistically significant and clinically meaningful improvement in overall survival versus neoadjuvant chemotherapy alone.
Dr. Sandip P. Patel from the University of California, San Diego Health, expressed excitement about "the progress being made across thoracic malignancies, including the use of immunotherapy and targeted therapy in the neoadjuvant non-small cell lung cancer setting, particularly regarding OS in the phase 3 CheckMate 816 trial."
This builds on previous data showing that the median event-free survival was 31.6 months with the combination versus 20.8 months with chemotherapy alone, and the pathological complete response rate was 24% with nivolumab plus chemotherapy compared to just 2.2% with chemotherapy alone.
Novel Approaches for HER2-Mutant NSCLC
The SOHO-01 trial (Abstract 8504) will present updated data on BAY 2927088, a dual EGFR and HER2 inhibitor, in patients with advanced HER2-mutant NSCLC. Dr. Joshua K. Sabari from NYU Grossman School of Medicine noted that historical objective response rates have been in the 70% range.
"What's different between zongertinib and the BAY 2927088 asset is that BAY 2927088 is an EGFR and HER2 inhibitor. You do have EGFR wild-type inhibition for BAY 2927088, whereas zongertinib is really HER2 selective," Dr. Sabari explained, noting that the toxicity profile for BAY 2927088 includes higher rates of gastrointestinal toxicity.
Addressing EGFR-Mutated NSCLC Resistance
The phase 3 HERTHENA-Lung02 study (Abstract 8506) will present data on patritumab deruxtecan (HER3-DXd) in EGFR-mutated advanced NSCLC after progression on third-generation EGFR TKIs.
Dr. Susan C. Scott from Johns Hopkins University School of Medicine commented, "If [HER3-DXd can] improve progression-free survival, this could offer a new alternative for EGFR-mutated NSCLC after resistance to first-line therapy with a TKI, saving chemotherapy for later lines."
Additionally, the phase 3 SACHI study (Abstract LBA8505) will present results on savolitinib combined with osimertinib versus chemotherapy in EGFR-mutant and MET-amplification advanced NSCLC after disease progression on EGFR TKIs. Interim results indicated that the combination therapy met its predefined progression-free survival endpoint, leading to priority review in China.
Novel Approaches in Locally Advanced NSCLC
The phase 2 InTRist trial (Abstract 8012) explores a novel approach in locally advanced, unresectable stage III NSCLC, examining whether an induction approach with the PD-1 inhibitor toripalimab-tpzi (Loqtorzi) and chemotherapy, followed by concurrent chemoradiotherapy and consolidation toripalimab, can outperform the current standard established by the PACIFIC trial.
"The outcomes of this trial could reshape treatment paradigms for a significant subset of NSCLC patients," noted Dr. Desai.
Precision Medicine Approaches
Abstract 8515 will present data on plasma-guided adaptive first-line chemoimmunotherapy for NSCLC. Dr. Scott expressed enthusiasm for this approach: "This type of novel, adaptive biomarker strategy is the future of precision oncology and the direction we need to be moving the field for our patients."
Other notable presentations include the NeoADAURA trial (Abstract 8001) evaluating neoadjuvant osimertinib with or without chemotherapy versus chemotherapy alone in resectable EGFR-mutant NSCLC, and the KRYSTAL-7 study (Abstract 8500) on first-line adagrasib with pembrolizumab in KRAS G12C-mutated NSCLC.
The 2025 ASCO Annual Meeting promises to deliver practice-changing data across the spectrum of lung cancer, with particular emphasis on novel targeted therapies, immunotherapy combinations, and perioperative treatment approaches that could significantly improve outcomes for patients with both SCLC and NSCLC.
