Editor’s Note: The 2025 American Society of Clinical Oncology (ASCO) Annual Meeting was held from May 30 to June 3 in Chicago, USA. Recognized as the largest and most prestigious global event in clinical oncology, ASCO brings together physicians, researchers, patient advocates, industry leaders, and media from around the world to spotlight the latest research and clinical trial results. This year, several studies from the team led by Dr. Li Zhang at the Sun Yat-sen University Cancer Center were selected for presentation. Oncology Frontier had the opportunity to speak with Dr. Zhang about his team’s contributions and key highlights from the conference. The following is a curated summary for our readers.Breakthroughs in ADC Research by Dr. Zhang’s Team
At ASCO 2025, three oral presentations from Dr. Zhang’s team were selected, all focused on the clinical application of antibody-drug conjugates (ADCs) in lung cancer. One of the featured studies, OptiTROP-Lung03, presented by Dr. Li Zhang himself, compared Sac-TMT with docetaxel in previously treated patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC).
EGFR tyrosine kinase inhibitors (TKIs) have transformed the treatment landscape for EGFR-mutant NSCLC, significantly prolonging survival. However, acquired resistance remains a major hurdle. For patients who have developed resistance, existing treatment options offer limited efficacy. In this randomized controlled trial, the Sac-TMT group showed markedly improved objective response rate (ORR), median progression-free survival (mPFS), and overall survival (OS) compared with the docetaxel group. Moreover, the incidence of grade ≥3 treatment-related adverse events (TRAEs) was lower (56.0% vs. 71.7%), and no interstitial lung disease (ILD) was reported.
These results suggest that Sac-TMT, a TROP2-directed ADC, offers both superior efficacy and manageable safety in patients with EGFR-mutant advanced NSCLC who have previously received EGFR-TKIs and platinum-based chemotherapy. It may become a new standard of care for this population. Notably, this study has been accepted for publication in the British Medical Journal (BMJ), which currently holds an impact factor of 93.6.
In addition, Dr. Yunpeng Yang and Dr. Yan Huang from the same team shared new findings on iza-bren, a bispecific ADC targeting both EGFR and HER3. Their research explored its potential in treating NSCLC with uncommon driver mutations (such as EGFR exon 20 insertions and KRAS G12C mutations) and in small cell lung cancer (SCLC).
In patients with rare NSCLC mutations, the results were encouraging. Among seven patients with EGFR exon 20 insertions, six (85.7%) achieved confirmed partial responses. Among eight patients with KRAS G12C mutations, three had confirmed responses, and one additional case was pending confirmation. Common hematologic toxicities, such as anemia and leukopenia, were controllable, with a low discontinuation rate of 2.7%. Only one patient experienced grade 2 ILD, and no new safety signals were observed—supporting further clinical investigation.
Encouraging results were also observed in pretreated SCLC patients, with an overall ORR of 55.2%, a confirmed ORR of 44.8%, and a median OS of 12.0 months. Among patients who had received only first-line treatment with PD-L1 inhibitors plus platinum chemotherapy (n=20), the confirmed ORR was as high as 75.0%, with a median OS of 15.1 months. TRAEs were primarily hematologic (e.g., anemia, neutropenia), manageable with supportive care. While two infection-related deaths were reported, no ILD occurred, and the treatment was deemed tolerable. A phase III trial for this subgroup is now underway, potentially offering a new option for SCLC.
China’s Expanding Influence in Global Lung Cancer Research
At this year’s ASCO meeting, research from Chinese teams was prominently featured. For instance, Dr. Baohui Han and his team at Shanghai Chest Hospital presented the CAMPASS study, which showed that first-line treatment with anti-angiogenic agents combined with immunotherapy significantly improved progression-free survival (PFS) in PD-L1–positive advanced NSCLC, with good tolerability.
In the ADC space, Dr. Shun Lu also from Shanghai Chest Hospital led the TROPION-Lung14 study. This study evaluated the combination of the TROP2-targeted ADC Dato-DXd and Rilvegostomig as first-line therapy for advanced or metastatic NSCLC. The combination demonstrated a safety profile consistent with either agent alone and showed promising antitumor activity across all PD-L1 expression levels.
Overall, nearly half of the oral presentations in lung cancer at ASCO 2025 came from Chinese researchers. This reflects not only the growing research capacity in China but also the increasing global impact of Chinese oncology experts. The continued rise of Chinese contributions to international platforms underscores a new era in which Chinese insights and innovations are shaping the future of lung cancer diagnosis and treatment.
Trends and Emerging Directions in Lung Cancer Treatment
Reflecting on the lung cancer studies presented at this year’s ASCO Annual Meeting, I believe three major trends are shaping the direction of clinical practice in this field.
First, as previously discussed, ADCs have demonstrated significant clinical potential as a more precise therapeutic option, not only in non-small cell lung cancer (NSCLC) but also in small cell lung cancer (SCLC). The growing body of data highlights their emerging role in redefining treatment standards across various subtypes.
Second, in the realm of immunotherapy, novel modalities such as bispecific antibodies—particularly bispecific T-cell engagers (BiTEs)—are beginning to show promising efficacy. These therapies, often employed in combination regimens, are advancing rapidly. Several studies have shown encouraging results for tarlatamab in the treatment of SCLC. Preliminary findings from the DeLLphi-304 study demonstrated that tarlatamab significantly improved overall survival (OS), progression-free survival (PFS), and patient-reported outcomes (PROs) in patients with SCLC whose disease had progressed during or after initial platinum-based chemotherapy. Tarlatamab also displayed a favorable safety and tolerability profile compared with chemotherapy, establishing a potential new standard of care for this population.
Third, KRAS G12C mutation represents a known negative prognostic factor in NSCLC. In the field of targeted therapy, substantial progress has been made in treating KRAS G12C-mutant NSCLC—both with monotherapies and combination strategies.
In terms of monotherapy, Dr. Jie Wang from the Cancer Hospital, Chinese Academy of Medical Sciences, presented the main findings of a phase II trial evaluating sosimerasib in previously treated patients with KRAS G12C-mutated NSCLC. The study demonstrated that sosimerasib exhibited strong antitumor activity and manageable safety in patients with locally advanced or metastatic disease.
The S1900E study investigated the influence of co-mutations on the efficacy of sotorasib monotherapy in patients with advanced or relapsed KRAS G12C-mutated NSCLC. The results showed that co-mutation with TP53 did not affect treatment efficacy. However, co-mutation with STK11 was associated with significantly reduced efficacy, offering valuable guidance for future patient stratification and personalized treatment strategies.
On the combination therapy front, the KRYSTAL-7 study showed that adagrasib plus pembrolizumab as first-line treatment for advanced or metastatic KRAS G12C-mutant NSCLC delivered favorable efficacy and safety. Notably, patients with PD-L1 expression ≥50% experienced more pronounced benefits. Similarly, the LOXO-RAS-20001 study demonstrated promising antitumor activity and good tolerability for olomorasib combined with pembrolizumab in the first-line setting for locally advanced or metastatic KRAS G12C NSCLC.
KRAS G12C has long been considered a challenging target among driver mutations in NSCLC. Continued research is eagerly anticipated, with the goal of bringing more effective treatment options to this difficult-to-treat patient population.
Professor Li Zhang
Chief Lung Cancer Specialist
Doctoral Supervisor and Senior Professor
Director of Medical Oncology, Sun Yat-sen University Cancer Center
- Chair, Cancer Rehabilitation and Palliative Care Committee, Chinese Anti-Cancer Association (CACA)
- Chair-Elect, Clinical Oncology Drug Research Committee, CACA
- Chair, Immunotherapy Expert Committee, Chinese Society of Clinical Oncology (CSCO)
- Vice Chair, NSCLC Expert Committee, CSCO
- Vice Chair, Oncology Supportive and Rehabilitative Care Committee, CSCO
- Chair, Clinical Research Branch, Guangdong Medical Association
- Chair, Precision Medicine Committee, Guangdong Clinical Medical Association
