The American Society of Clinical Oncology (ASCO) 2026, held from May 29 to June 2, 2026, served as a critical platform for the unveiling of pivotal clinical trial data, offering a glimpse into the future of non-small cell lung cancer (NSCLC) treatment. Amidst intense scientific scrutiny and anticipation, presentations on emerging therapies generated significant discussion, particularly highlighting Eli Lilly’s positive advancements with Retevmo in the adjuvant setting and the complex reception of Summit Therapeutics and Akeso’s ivonescimab in first-line squamous NSCLC. The congress underscored the rapid evolution of NSCLC therapeutics, a field characterized by fierce competition and the relentless pursuit of improved patient outcomes.
Summit Therapeutics and Akeso’s Ivonescimab: A Promising but Contentious Debut in Squamous NSCLC
A significant portion of the ASCO 2026 discourse revolved around the Phase III HARMONi-6 trial, which evaluated ivonescimab (Idafang), a novel bispecific antibody targeting both PD-1 and VEGF-A, in combination with chemotherapy. The trial pitted ivonescimab against BeOne Medicines’ Tevimbra (tislelizumab), another PD-1 monoclonal antibody, also in combination with chemotherapy, for patients with previously untreated advanced or metastatic squamous NSCLC. This specific histological subtype of NSCLC, representing approximately 25-30% of all NSCLC cases, is historically associated with a poorer prognosis, making advancements in its treatment particularly crucial.
The HARMONi-6 trial, conducted across 50 sites in China, revealed compelling survival data. Patients receiving the ivonescimab and chemotherapy regimen demonstrated a median overall survival (OS) of 27.9 months, a statistically significant improvement compared to the 23.7 months observed in the Tevimbra arm. This translated to a notable 34% reduction in the risk of death (Hazard Ratio [HR]: 0.66; 95% Confidence Interval [CI]: 0.50, 0.87). This OS benefit positions ivonescimab as a potentially groundbreaking therapy in this challenging patient population.
Akeso has already secured two regulatory approvals for ivonescimab from China’s National Medical Products Administration (NMPA). The first approval was for patients with EGFR-mutated non-squamous metastatic NSCLC who have progressed after EGFR-tyrosine kinase inhibitor (TKI) therapy. The second approval was for first-line treatment of PD-L1-positive locally advanced or metastatic NSCLC, excluding EGFR and ALK mutations. Summit Therapeutics holds the rights to market and develop ivonescimab in key global markets, including the US, Canada, Europe, Japan, Latin America, the Middle East, and Africa, underscoring the global ambitions for this bispecific antibody.
However, the positive survival outcomes were met with a degree of caution and critical analysis from the oncology community. Several critical questions were raised regarding the translatability of the HARMONi-6 findings to a broader, global squamous NSCLC patient demographic. A notable concern is the exclusion of patients over the age of 75 from the trial. Given that the average age of a lung cancer patient in the United States is 70, and recognizing that VEGF inhibitors have historically shown increased toxicities in older patient populations, this exclusion raises questions about the drug’s real-world applicability and safety profile in a more elderly cohort.
Furthermore, the demographic makeup of the trial population presented another point of contention. The proportion of female squamous NSCLC patients in China is lower than the global average, standing at approximately 10% compared to 20% worldwide. This disparity, reflected in the HARMONi-6 patient cohort, has led to concerns about how the drug’s efficacy and tolerability might differ in populations with a higher representation of female patients.
The safety profile of ivonescimab also warrants careful consideration. While grade 3 or higher treatment-related adverse events (TRAEs) were comparable between the two arms (69.2% for ivonescimab vs. 58.9% for Tevimbra), there was a notable increase in VEGF-related events in the ivonescimab arm. Hemorrhage, for instance, occurred in 24.8% of patients receiving ivonescimab, compared to 12.1% in the Tevimbra arm. While discontinuations due to TRAEs were relatively low and comparable across both groups (5.3% for ivonescimab vs. 4.5% for Tevimbra), and TRAEs leading to death were also similar (3.8% vs. 4.2%), the increased incidence of hemorrhage necessitates careful monitoring and management.
Despite these concerns, Akeso and Summit are strategically positioned to be early movers in the PD-(L)1 and VEGF bispecific landscape for NSCLC. A confirmatory global Phase III trial, HARMONi-3, is currently underway. This trial aims to further evaluate ivonescimab in combination with chemotherapy against pembrolizumab plus chemotherapy in both first-line advanced squamous and non-squamous NSCLC, irrespective of PD-L1 expression. This broader trial design is expected to provide more comprehensive data applicable to a wider patient population.
The competitive landscape for first-line squamous NSCLC is intensifying. Bristol Myers Squibb/BioNTech and Pfizer also presented data at ASCO 2026 on their respective VEGF-PD-(L)1 bispecific antibodies, pumilatamig and SSGJ-707. However, OS data for these agents was not yet mature at the time of presentation, suggesting that Akeso and Summit might indeed secure the first FDA approval for a PD-(L)1 and VEGF bispecific in NSCLC.
Beyond bispecific antibodies, antibody-drug conjugates (ADCs) in combination with PD-(L)1 inhibitors are emerging as significant contenders. AstraZeneca and Daiichi Sankyo’s Datroway (datopotamab deruxtecan) in combination with Imfinzi (durvalumab), and Merck & Co.’s sacituzumab tirumotecan with Keytruda (pembrolizumab), have shown promising results. The Phase III OptiTROP-Lung05 trial, evaluating sacituzumab tirumotecan and Keytruda, presented positive progression-free survival (PFS) results at ASCO 2026, further highlighting the dynamic and multifaceted nature of first-line NSCLC treatment.
The economic implications of these developments are substantial. According to GlobalData’s analyst consensus forecast, ivonescimab is projected to achieve global sales of $11 billion by 2032. In comparison, pumilatamig and SSGJ-707 are forecasted to reach $3.2 billion and $710 million, respectively, in the same year. This forecast underscores the immense market potential of effective therapies in the highly competitive first-line NSCLC setting.
Eli Lilly’s Retevmo: Expanding Horizons in Adjuvant RET Fusion-Positive NSCLC
In a significant development for a distinct subset of NSCLC patients, Eli Lilly presented robust data from the Phase III LIBRETTO-432 trial, showcasing the efficacy of Retevmo (selpercatinib) in the adjuvant setting for early-stage (IB-IIIA) RET fusion-positive (RET+) NSCLC. This presentation, delivered during a plenary session at ASCO 2026, marks a pivotal step in potentially expanding the therapeutic armamentarium for patients who have undergone surgery.
RET fusions are a relatively rare but potent oncogenic driver alteration in NSCLC, identified in approximately 1-2% of all NSCLC cases. Their prevalence is even lower in other solid tumors, such as colorectal and breast cancer, where they account for less than 1%. Retevmo is currently approved for first-line metastatic RET+ NSCLC and for all RET+ solid tumors lacking satisfactory alternative treatment options. Despite its broad tumor-agnostic approval, the adoption of Retevmo has been somewhat constrained by the rarity of the genetic alteration and the reliance on companion diagnostics for its detection. Eli Lilly’s presentation of the LIBRETTO-432 data signals a strategic effort to broaden the indication for Retevmo, thereby incentivizing increased mutation testing rates across a wider patient population.
The LIBRETTO-432 trial enrolled 151 patients and randomized them in a 1:1 ratio to receive either Retevmo or a placebo for three years following surgical resection. While stage IB patients were included in the overall enrollment, the efficacy analysis specifically focused on stage II-IIIA patients. The results were striking: median event-free survival (EFS) was not reached in the Retevmo arm, indicating a substantial and sustained benefit. In contrast, the placebo arm showed a median EFS of 31.8 months. This difference translated to a highly significant reduction in the risk of disease recurrence or death, with a hazard ratio of 0.172 (95% CI: 0.058, 0.509; p=0.0003).
Quantitatively, the two-year EFS rates further underscored Retevmo’s impact, with 91.5% of patients on Retevmo remaining disease-free compared to 61.1% in the placebo group. Tragically, three deaths were reported during the trial, all occurring in the placebo arm due to disease progression, highlighting the aggressive nature of untreated advanced NSCLC.
However, the improved efficacy came with a discernible toxicity profile. Treatment-emergent adverse events (TEAEs) of grade 3 or higher were reported in 66.7% of patients receiving Retevmo, a significant increase compared to the 23.7% observed in the placebo group. This higher incidence of severe TEAEs led to a notable proportion of patients discontinuing treatment, with 17.3% of those on Retevmo discontinuing therapy. This observation raises important questions about potential dose optimization or the duration of adjuvant treatment, suggesting that the current regimen might be challenging for some patients to tolerate over the full three-year period.
The positive outcomes of LIBRETTO-432 are poised to significantly enhance the treatment options available in the adjuvant NSCLC setting. Currently, adjuvant immunotherapy, such as Merck & Co.’s Keytruda (pembrolizumab), is a standard of care. However, its efficacy can be diminished in patients with specific driver mutations like RET fusions. Similarly, TKIs targeting EGFR, such as AstraZeneca’s Tagrisso (osimertinib) or Pfizer’s Alecensa (alectinib), are available for specific genetic alterations but do not directly address RET fusions. Retevmo’s potential to fill this gap for RET fusion-positive patients is substantial.
A crucial prerequisite for maximizing the benefit of these findings for patients is the widespread adoption of genetic testing for RET fusions in individuals diagnosed with early-stage NSCLC. Increased testing rates are essential to identify eligible candidates who can benefit from adjuvant Retevmo.
In terms of market competition, Retevmo appears to hold a strong position in this niche. Its primary competitor, Rigel’s Gavreto (pralsetinib), has faced commercial challenges and is not currently undergoing trials in the adjuvant setting. This leaves Eli Lilly with a potential monopolistic advantage in treating this specific, albeit small, patient population with adjuvant therapy. GlobalData’s analyst consensus forecasts Retevmo to generate $665 million in global sales by 2032, while Gavreto is projected to reach $365 million in the same year. These figures, while substantial, reflect the limited prevalence of RET fusions within the broader NSCLC market.
The ASCO 2026 congress has thus provided a dynamic snapshot of progress and ongoing challenges in NSCLC research. While Summit and Akeso’s ivonescimab presents a potentially transformative option for squamous NSCLC, its broader applicability requires further validation through global trials. Conversely, Eli Lilly’s Retevmo offers a more definitive and immediate advancement in the adjuvant setting for a genetically defined subset of NSCLC patients, underscoring the increasing importance of precision medicine in oncology. The coming years will undoubtedly witness further innovation and refinement in the treatment of this complex and often devastating disease.
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