Merck’s early PD-1/VEGF data competitive in lung cancer, but Summit ‘looms large’

Merck's Bispecific Antibody Shows Competitive Early NSCLC Data

Merck and Sino Biopharmaceutical's investigational anti-PD-1/VEGF bispecific antibody, MK-2010, showed competitive early-stage results in a Phase 1/2 study for non-small cell lung cancer (NSCLC). Presented at the American Association for Cancer Research (AACR) annual meeting, the therapy achieved an unconfirmed overall response rate (ORR) of 55% in treatment-naïve patients and 44% in second-line or later patients. These findings position MK-2010 to potentially rival Summit Therapeutics' ivonescimab, which is currently under FDA review for NSCLC, though analysts note Merck still faces a significant competitive landscape.

• Merck's bispecific antibody, MK-2010, demonstrated promising efficacy in a Phase 1/2 study for non-small cell lung cancer. It achieved an unconfirmed overall response rate of 55% in patients who had not undergone prior lines of treatment and 44% in those receiving it as a second-line or later option, indicating its potential across different treatment settings.
• The data for MK-2010 are largely in line with Summit Therapeutics and Akeso's ivonescimab, a PD-1/VEGF bispecific antibody currently under FDA review for NSCLC with a decision expected in November. Ivonescimab previously showed significant progression-free survival benefits over Keytruda in a Phase 3 study, setting a high benchmark for new entrants.
• While analysts acknowledge MK-2010's competitive early data, they emphasize the need for high ORRs to translate into survival outcomes in later-stage studies to truly compete. Some view Summit as substantially ahead, while others believe Merck's strong portfolio, including potential antibody-drug conjugate combinations, could help it leapfrog the competition.
• MK-2010 originated from a November 2024 partnership between Merck and LaNova Medicines, valued at $588 million upfront and up to $2.7 billion in milestones. Subsequently, Sino Biopharmaceutical acquired LaNova in July 2025 for up to $951 million, highlighting the significant investment and strategic interest in this bispecific antibody modality.

MK-2010's Phase 1/2 Efficacy in Non-Small Cell Lung Cancer

The Phase III PAPILLON study demonstrated significant efficacy benefits for amivantamab-chemotherapy as first-line treatment in patients with EGFR exon 20 insertion-mutated NSCLC. In this randomized trial of 308 participants, the combination significantly prolonged progression-free survival over chemotherapy alone, with median time to treatment discontinuation of 13.2 versus 7.5 months (HR 0.38, 95% CI 0.28-0.51; p<0.0001). The study also showed favorable crossover-adjusted overall survival with hazard ratios ranging from 0.52-0.60, though detailed safety outcomes were not reported in the available data.

Meta-analyses of tislelizumab, a PD-1 inhibitor developed in China, revealed substantial clinical benefits both as monotherapy and in combination with chemotherapy for NSCLC patients. The analysis demonstrated improved event-free survival (RR=1.40, 95% CI: 1.19-1.65) and reduced risk of disease progression or death by 41% (HR=0.59, 95% CI: 0.52-0.67). Overall survival risk was reduced by 35% (HR=0.65, 95% CI: 0.59-0.73), with single-arm studies showing a 1-year overall survival rate of 73.8%. Safety profiles were generally manageable, with more frequent elevations in ALT/AST, hypothyroidism, and rash, but fewer cases of anemia and neutropenia compared to chemotherapy.

A retrospective analysis of MET tyrosine kinase inhibitors (tepotinib and capmatinib) in 49 patients with METex14-altered NSCLC demonstrated modest but meaningful efficacy outcomes. Patients receiving first-line MET-TKI treatment achieved a median PFS of 5.6 months, median OS of 21.3 months, and ORR of 48.6%. However, the analysis revealed significant limitations in patients with poor performance status (PS ≥2), who experienced substantially shorter outcomes with median PFS of 0.95 months and median OS of 1.3 months, highlighting the importance of patient selection in this treatment approach.

Merck's Strategic Combinations for MK-2010 in NSCLC

Recent clinical trials in non-small cell lung cancer (NSCLC) are exploring diverse combination therapy approaches that demonstrate promising efficacy across multiple therapeutic modalities. Immune checkpoint inhibitor combinations represent a major focus, with tislelizumab plus chemotherapy showing particularly robust results in advanced squamous NSCLC, achieving median overall survival of 26.1 months with paclitaxel/carboplatin and 23.3 months with nab-paclitaxel/carboplatin, compared to 19.4 months for chemotherapy alone. Additionally, ICI-chemotherapy combinations for NSCLC with bone metastases demonstrated superior bone metastasis response rates (43.4% vs. 20.5%) and significantly improved survival outcomes compared to ICI monotherapy.

Targeted therapy combinations are yielding encouraging results, particularly in molecularly defined patient populations. The combination of trametinib (MEK inhibitor) with anlotinib (pan-RTK inhibitor) for advanced non-G12C KRAS-mutant NSCLC achieved impressive response rates of 65-69.2%, with median progression-free survival of 11.5 months and overall survival of 15.5 months in phase Ib studies. For patients with specific molecular alterations, tepotinib demonstrated safety and efficacy in the neoadjuvant/adjuvant setting for MET Ex14 mutations, while dirozalkib showed remarkable activity in ALK inhibitor-naive patients with ALK-rearranged NSCLC, achieving 89.3% objective response rate.

Innovative combination strategies are expanding beyond traditional approaches, with immunotherapy plus anti-angiogenic agents showing substantial promise. Tislelizumab combined with anlotinib achieved a 55.17% objective response rate and 96.55% disease control rate in advanced pulmonary sarcomatoid carcinoma, with manageable toxicity profiles. Novel approaches including nimotuzumab with nivolumab for EGFR/PD-1 dual targeting, and emerging combinations like cannabidiol with bevacizumab in preclinical models, demonstrate the breadth of investigational strategies being pursued to optimize therapeutic outcomes in NSCLC patients across diverse molecular and histological subtypes.

Merck's Bispecific Antibody Ignites NSCLC Competitive Landscape

The recent presentation of early-stage data for Merck and Sino Biopharmaceutical's investigational bispecific antibody, MK-2010, at AACR marks a significant moment in the ongoing evolution of non-small cell lung cancer (NSCLC) treatment. With an unconfirmed overall response rate (ORR) of 55% in treatment-naïve patients and 44% in second-line or later patients, MK-2010 is poised to enter a highly competitive therapeutic arena. This dual-targeting approach, simultaneously inhibiting PD-1 and VEGF, represents a sophisticated strategy to enhance anti-tumor immunity and overcome resistance mechanisms often observed with single-agent immunotherapies.

The competitive landscape is already robust, with several immune checkpoint inhibitors (ICIs) and emerging bispecific antibodies. Summit Therapeutics' ivonescimab, another PD-1/VEGF bispecific antibody, has demonstrated compelling efficacy, including a median progression-free survival (PFS) of 11.1 months versus 5.8 months for pembrolizumab in PD-L1-positive advanced NSCLC, and an ORR of 50.6% when combined with chemotherapy in EGFR-TKI-treated NSCLC. MK-2010's early ORR figures suggest it could be a strong contender, potentially offering a new option for patients, particularly those who have progressed on prior therapies, a setting where optimal treatment options remain limited.

However, several critical considerations must be addressed as MK-2010 progresses. While ORR is an encouraging early indicator, studies consistently show that it is not a valid surrogate for overall survival (OS) in anti-PD-1/PD-L1 trials. Therefore, robust Phase 3 data with OS as a primary endpoint will be crucial to confirm long-term clinical benefit and differentiate MK-2010 in the market. Furthermore, combination therapies, including bispecific antibodies, often carry a higher risk of grade 3 or higher treatment-related adverse events compared to monotherapies. Careful monitoring and management of these toxicities will be paramount. Finally, the efficacy of ICIs can vary significantly across different NSCLC subgroups, such as those with varying PD-L1 expression levels or specific oncogenic drivers. Future trials will need to clearly delineate MK-2010's performance in these diverse patient populations to optimize its clinical application. The success of MK-2010 will depend on its ability to demonstrate sustained survival benefits with a manageable safety profile across a broad spectrum of NSCLC patients, ultimately reshaping treatment paradigms and offering new hope in this challenging disease.