The annual American Society of Clinical Oncology (ASCO) congress, a cornerstone event for the global oncology community, convened in Chicago, drawing thousands of researchers, clinicians, and industry leaders to dissect the latest advancements in cancer treatment. This year, the spotlight on lung cancer, the world’s leading cause of cancer-related mortality and morbidity as per the World Health Organization (WHO), was particularly intense. With numerous targeted therapies and novel immunotherapeutic agents in various stages of development, ASCO 2026 served as a critical platform for presenting groundbreaking clinical trial data, offering renewed hope and potential paradigm shifts in the management of this devastating disease.
The congress buzzed with a flurry of significant readouts from major pharmaceutical players including Bristol Myers Squibb (BMS), BioNTech, Pfizer, Johnson & Johnson (J&J), and Kelun Biotech, among others. These presentations spanned a range of lung cancer subtypes, from non-small cell lung cancer (NSCLC) to specific genetic mutations, highlighting progress in both established and emerging therapeutic modalities. The influx of data underscored a dynamic and rapidly evolving field, with a clear trajectory towards more personalized and effective treatment strategies.
BMS and BioNTech Unveil Potent Bispecific in Frontline NSCLC
A highly anticipated presentation came from Bristol Myers Squibb (BMS) and its partner BioNTech, who shared interim Phase II data for their novel PD-L1/VEGF bispecific antibody, pummitamig. The data, derived from the global Phase II/III ROSETTA Lung-02 study (NCT06712316), investigates pummitamig in combination with chemotherapy as a first-line treatment for patients with untreated non-small cell lung cancer (NSCLC).
Among the 40 response-evaluable patients enrolled in this specific cohort, encompassing both squamous and non-squamous NSCLC histologies, pummitamig demonstrated a remarkable overall response rate (ORR) of 70%. This translated into two patients achieving a complete response (CR) and 26 patients experiencing a partial response (PR). Notably, the squamous cell carcinoma subset exhibited an even higher ORR, with nine out of eleven (81.8%) patients achieving a response on a 1400mg dose of pummitamig.
The safety profile of pummitamig also garnered attention. While 44.2% of patients experienced Grade 3 or higher adverse events (AEs), only 18.6% of these were deemed related to pummitamig. This rate of treatment-related AEs leading to discontinuation is considered numerically lower than the approximately 23% observed with certain Keytruda (pembrolizumab) combinations, according to analysts at Jefferies.
In their research notes, Jefferies analysts described the early, first-line NSCLC dataset for pummitamig as "just as good" as that of ivonescimab, a late-stage PD-1/VEGF bispecific candidate developed by MSD (Merck & Co) and Kelun Biotech. Ivonescimab’s prominence was amplified by its selection for a plenary session at ASCO 2026, a testament to its perceived significance. The analysts further commented, "We currently don’t see a clear differentiation on efficacy or safety across the different PD-(L)1xVEGF agents & continue to believe that long-term differentiation will hinge on combinations w/ novel ADCs that can expand the therapeutic window." This sentiment suggests that while current head-to-head comparisons are challenging, future advancements may lie in synergistic combinations.
It is worth noting that Pfizer’s own PD-L1/VEGF bispecific, PF-08634404, has previously reported a confirmed ORR (cORR) ranging from 64-75% in both squamous and non-squamous settings, irrespective of PD-L1 expression, during a study conducted in China for frontline NSCLC. This competitive landscape underscores the intense research and development efforts in this therapeutic area.
Kelun Biotech Presents Comprehensive Data Package, Poised for Regulatory Submissions
Kelun Biotech emerged as a significant contributor to the ASCO 2026 discourse, not only through the highly anticipated readout of ivonescimab but also by announcing its intention to file for Chinese regulatory approval for its selective RET inhibitor, lunbotinib fumarate. This filing is based on pivotal study results in RET-positive NSCLC.
The Phase II trial for lunbotinib fumarate enrolled 163 patients, comprising both treatment-naïve and pre-treated individuals. The study demonstrated a confirmed ORR of 81.3% in treatment-naïve patients and an impressive 87.1% in pre-treated patients. While the median progression-free survival (PFS) for the treatment-naïve group has not yet been reached, pre-treated patients achieved a median PFS of 27.5 months.
Beyond its efficacy in controlling disease progression, lunbotinib fumarate also showed promise in managing central nervous system (CNS) metastases, a common and often challenging complication of lung cancer. Among the 40 patients with brain metastases, the intracranial response rate (ICR) reached 30%, indicating a potential benefit for patients with advanced disease impacting the brain.
The tolerability of lunbotinib fumarate was also favorable, with the majority of treatment-emergent adverse events (TEAEs) being of Grade 1 or 2. Crucially, only a minimal 1.2% of patients discontinued treatment due to a TEAE, suggesting a manageable safety profile for long-term administration.
Following these promising results, Kelun plans to submit an application to China’s National Medical Products Administration (NMPA) for the approval of lunbotinib fumarate in RET-positive NSCLC. Concurrently, British biotechnology firm Ellipses Pharma will continue to explore the drug’s potential in a global Phase II trial (NCT05443126). If approved on a global scale, lunbotinib fumarate would enter a market currently served by established tyrosine kinase inhibitors (TKIs) like Eli Lilly’s Retevmo (selpercatinib) and Roche & Blueprint Medicines’ Gavreto (pralsetinib), offering another therapeutic option for patients with this specific genetic alteration.
Johnson & Johnson Explores Rybrevant-Lazertinib Synergy in Atypical EGFR Mutations
Johnson & Johnson (J&J) presented updated data from its open-label Phase I/Ib CHRYSALIS-2 study (NCT04077463), focusing on the combination of Rybrevant (amivantamab) and Lazertinib (lazertinib) in patients with EGFR-mutated NSCLC. The study specifically aimed to assess the duo’s efficacy in patients with atypical EGFR mutations, a subset that often faces poorer prognoses compared to those with common mutations.
While J&J had previously reported ORR data, a primary endpoint of the study, this presentation included crucial overall survival (OS) data. The results revealed a median OS of nearly three and a half years. At the three-year mark, 55% of patients remained alive, with 46% still alive at four years. These long-term survival figures represent a significant advancement for patients with atypical EGFR mutations.
The Rybrevant-Lazertinib combination demonstrated consistent clinical activity across various atypical EGFR mutation subgroups. Furthermore, patients generally remained on treatment for extended periods, with 41% receiving Rybrevant for two years or longer. This sustained treatment duration was partly attributed to the drug combination’s favorable safety and tolerability profile, with most TEAEs being Grades 1 or 2.
These findings are particularly impactful given that atypical EGFR mutations account for approximately 10-20% of EGFR-mutated NSCLC cases and are often associated with less favorable outcomes. Joel Neal, the principal investigator of the CHRYSALIS-2 study and a professor of medicine at Stanford, commented on the findings, stating, "Results from this trial suggest the potential for more durable disease control." He further noted that the long-term outcomes of the study could potentially reshape how healthcare professionals approach the management of this specific subtype of lung cancer. Rybrevant and Lazertinib have already received regulatory approval in the US, Europe, and the UK for advanced or metastatic NSCLC with common EGFR mutations (exon 19 deletions or exon 21 L858R substitution mutations), and these new data expand their potential utility.
Pfizer’s Lorbrena Achieves Unprecedented Long-Term PFS in ALK-Positive NSCLC
Pfizer also highlighted the long-term benefits of its ALK inhibitor, Lorbrena (lorlatinib), by presenting seven-year data from the pivotal Phase III CROWN trial (NCT03052608). This trial directly compared Lorbrena against its predecessor, Xalkori (crizotinib), in previously untreated patients with ALK-positive advanced or metastatic NSCLC.
The seven-year follow-up revealed a striking 55% likelihood of remaining alive without disease progression for patients treated with Lorbrena, a stark contrast to the 3% observed in the Xalkori arm. Crucially, the investigator-assessed median PFS had not yet been reached at this seven-year mark for the Lorbrena group, indicating sustained efficacy over an extended period.
A particularly significant finding was Lorbrena’s ability to prevent and control brain metastases. The drug demonstrated a remarkable 94% reduction in a patient’s risk of developing intracranial progression, addressing a critical unmet need in ALK-positive NSCLC management.
However, Jefferies analysts identified CNS toxicity as a "key drawback" of Lorbrena. The data indicated that 34% of patients required dose reductions, and 5% discontinued treatment due to CNS-related adverse events. Despite this, the overall long-term efficacy and CNS control remain compelling.
Tony Shu-Kam Mok, the principal investigator of the CROWN trial and chair of the clinical oncology department at the Chinese University of Hong Kong, remarked, "Observing this level of long-term benefit with a once-daily oral therapy, both in terms of sustained PFS and prevention of brain metastases underscores the significance of these results for the lung cancer community." The CROWN trial’s extended data solidify Lorbrena’s position as a first-line standard of care for ALK-positive NSCLC, offering patients the longest PFS reported to date in this setting.
The ASCO 2026 congress underscored the rapid pace of innovation in lung cancer therapeutics. The presentations of novel bispecific antibodies, targeted therapies for specific mutations, and long-term survival data from established treatments collectively paint a picture of an oncology landscape that is continuously advancing, offering greater hope and improved outcomes for patients worldwide. The continued collaboration between researchers, clinicians, and the pharmaceutical industry promises further breakthroughs in the fight against lung cancer.
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