Summit’s PD-1/VEGF to take center stage at ASCO, with wide impact for peers

Summit's Ivonescimab OS Data at ASCO to Reshape IO Landscape

Summit Therapeutics' Chinese partner Akeso is set to unveil overall survival (OS) data for their PD-1/VEGF bispecific asset, ivonescimab, at the American Society of Clinical Oncology (ASCO) meeting. This long-awaited readout from the Phase 3 HARMONi-6 study, which previously showed 11.14 months progression-free survival (PFS) for ivonescimab versus 6.9 months for the comparator in first-line advanced squamous NSCLC, is expected to significantly impact the immuno-oncology landscape. Analysts anticipate statistically significant improved OS, potentially reshaping the narrative around IO in NSCLC and influencing the strategies of rivals like Merck, Bristol Myers Squibb, and BioNTech, who also have similar assets or are pursuing alternative oncology approaches.

• Akeso and Summit Therapeutics will present crucial overall survival (OS) data for their PD-1/VEGF bispecific ivonescimab at the upcoming ASCO meeting. This follows previously reported progression-free survival (PFS) data from the Phase 3 HARMONi-6 study, which demonstrated ivonescimab's superiority with 11.14 months PFS compared to 6.9 months in the comparator arm for first-line advanced squamous non-small cell lung cancer (NSCLC) patients. The OS data will compare ivonescimab against BeOne’s Tevimbra and chemotherapy.
• BMO Capital Markets anticipates the HARMONi-6 plenary session to be a highlight of ASCO, expecting statistically significant improved overall survival with a hazard ratio between 0.65 and 0.72. While not expected to immediately dethrone Keytruda, positive data could initiate a shift in the immuno-oncology (IO) narrative for NSCLC. This readout is poised to have a ripple effect across the oncology space, influencing investor perceptions and strategic decisions for companies with similar assets.
• The ivonescimab data will provide insights into how PD-(L)1xVEGF bispecifics compete with established anti-PD-(L)1 agents like Merck’s Keytruda. Rivals such as Merck (with MK-2010 and sac-TMT), Bristol Myers Squibb and BioNTech (with pumitamig), Pfizer (with PFE-08634404), and AbbVie (with ABBV-1480) are also developing similar or alternative oncology assets. The success of ivonescimab could prompt re-evaluation of development priorities and partnership strategies among these major pharmaceutical players.
• Beyond NSCLC, analysts predict significant potential for PD-(L)1/VEGF bispecifics in other cancers, such as colorectal cancer, where Keytruda has faced challenges. The dual mechanism of blocking checkpoint inhibition and preventing tumor angiogenesis could overcome resistance mechanisms and enhance immune cell infiltration. This emerging modality is seen as a critical development in the lead-up to Keytruda's patent exclusivity loss in 2029, necessitating highly differentiated efficacy for new agents to succeed in a post-Keytruda market.

HARMONi-6: Unpacking Ivonescimab's Overall Survival Data in NSCLC

Recent clinical trials in NSCLC have demonstrated significant advances across multiple treatment settings and molecular subtypes. The following studies represent key developments in targeted therapy, immunotherapy combinations, and novel treatment approaches that are reshaping the therapeutic landscape.

• PAPILLON (Phase III, 2026) - Amivantamab-chemotherapy combination in EGFR exon 20 insertion-mutated NSCLC achieved median time to treatment discontinuation of 13.2 vs 7.5 months compared to chemotherapy alone (HR 0.38; p<0.0001), with crossover-adjusted overall survival showing favorable HRs of 0.52-0.60

• RATIONALE-307 (4-year follow-up, 2026) - Tislelizumab plus chemotherapy in advanced squamous NSCLC demonstrated median overall survival of 26.1 months vs 19.4 months for chemotherapy alone, with 4-year OS rates of 32.2% vs 19.2%; grade ≥3 treatment-emergent adverse events occurred in 89.2% vs 84.6%

• ORCHARD Platform Study (2026) - Osimertinib plus datopotamab deruxtecan post-osimertinib progression showed confirmed ORR of 43% (4 mg/kg) and 36% (6 mg/kg), with median PFS of 9.5 and 11.7 months respectively; grade ≥3 AEs occurred in 49% and 76% of patients

• Tislelizumab-Anlotinib (Phase II, 2026) - First-line combination in pulmonary sarcomatoid carcinoma achieved ORR of 55.17% with median PFS of 9.40 months and median OS of 14.37 months; grade 3-4 treatment-related AEs occurred in 27.59% of patients with no treatment-related deaths

• ALEX Final Analysis (2025) - Alectinib vs crizotinib in ALK-positive NSCLC showed median OS of 81.1 vs 54.2 months (HR 0.78), with particularly pronounced benefits in patients with CNS metastases (63.4 vs 30.9 months); median duration of response was 42.3 vs 11.1 months

• PD-1 Rechallenge Study (2026) - PD-1 plus chemotherapy after prior immunotherapy achieved ORR of 30.3% and median OS of 17.8 months compared to docetaxel monotherapy (15.9% ORR, 9.5 months OS); any-grade treatment-related AEs occurred in 84.8% vs 81.0% with no treatment-related deaths

Beyond NSCLC: The Broad Potential of PD-1/VEGF Bispecifics

Ivonescimab, a bispecific antibody targeting PD-1 and VEGF, is being evaluated across multiple cancer types beyond NSCLC, demonstrating the versatility of this dual mechanism approach. These trials employ diverse intervention models ranging from single-arm dose-escalation studies to randomized controlled trials, reflecting different stages of clinical development across various tumor types.

• Extensive-stage Small Cell Lung Cancer (SCLC): A dose-escalation study evaluated ivonescimab (3, 10, or 20 mg/kg every 3 weeks) combined with etoposide and carboplatin as first-line treatment in 35 patients, achieving an 80% confirmed objective response rate with dose-dependent efficacy ranging from 66.7% to 90.9%

• Luminal-type Breast Cancer: A single-center, prospective phase II trial using Simon's two-stage design is evaluating neoadjuvant stereotactic body radiotherapy combined with ivonescimab and chemotherapy in 50 Chinese patients, with pathological complete response as the primary endpoint

• Locally Advanced Pancreatic Cancer: A single-arm phase Ib/II study (NCT06844422) in 37 patients uses 3+3 dose-escalation methodology in phase Ib to establish the recommended phase II dose, followed by evaluation of ivonescimab combined with SBRT and modified FOLFIRINOX chemotherapy

• Advanced Solid Tumors: A multicenter, open-label phase I dose-escalation study across five Chinese hospitals evaluated ivonescimab monotherapy in 59 patients using various dosing regimens (3-30 mg/kg) administered every 2-3 weeks, establishing safety profiles across different tumor types

• Advanced Gastric Adenocarcinoma: Clinical experience includes case reports of ivonescimab monotherapy in elderly patients with PD-L1-high tumors, representing real-world application of sequential immunotherapy approaches in this indication

The Race for PD-1/VEGF Dominance in the Post-Keytruda Era

The literature reveals limited data on other bispecific antibodies targeting the same PD-1/VEGF mechanism as ivonescimab for advanced NSCLC. LY3415244 represents the only other identified bispecific antibody with a related dual checkpoint inhibition approach, though it targets TIM-3/PD-L1 rather than PD-1/VEGF pathways. Several other bispecific antibodies are approved for solid tumors but utilize different mechanisms of action.

Ivonescimab's OS Data: A New Frontier in NSCLC Immunotherapy

The upcoming overall survival (OS) data for ivonescimab in first-line advanced squamous non-small cell lung cancer (NSCLC) represents a pivotal moment for the immuno-oncology field. For years, PD-1 inhibitors have been foundational in NSCLC treatment, demonstrating significant benefits. However, ivonescimab, a novel bispecific antibody targeting both PD-1 and VEGF, has already shown a superior progression-free survival (PFS) compared to pembrolizumab in PD-L1-positive advanced NSCLC. This head-to-head comparison sets a high bar, and a positive OS readout would not only validate the synergistic potential of dual PD-1 and VEGF inhibition but could also fundamentally reshape the standard of care for this challenging patient population.

Such an outcome would send ripples across the competitive landscape, intensifying pressure on established players like Merck and Bristol Myers Squibb. It would underscore the strategic importance of developing next-generation multi-targeted immunotherapies, potentially accelerating research into other bispecific or combination approaches. Companies might be compelled to re-evaluate their pipelines and consider similar dual-mechanism strategies to remain competitive.

However, the path forward is not without considerations. Clinical data indicates that ivonescimab was associated with a higher rate of Grade 3 or higher treatment-related adverse events compared to pembrolizumab. While manageable, this increased toxicity profile necessitates careful patient selection and proactive management strategies, which could influence its real-world adoption. Furthermore, the pivotal HARMONi-2 study was conducted in China, and while the results are compelling, broader validation across diverse global populations will be crucial for widespread acceptance. The long-term durability of response and optimal treatment duration, common questions for all immunotherapies, will also be key factors in defining ivonescimab's ultimate role. Ultimately, a strong OS signal would cement the bispecific antibody platform as a powerful new frontier in cancer therapy, potentially ushering in an era of more potent and precisely targeted immuno-oncology agents.