Bispecific antibody boom: global trials, billion-dollar bets, and lung cancer doubts reshape oncology race

By mid-2026, Crescent Biopharma had actively launched its ASCEND Phase 1/2 trial for CR-001, a PD-1 x VEGF bispecific antibody, enrolling up to 290 patients across multiple solid tumors with initial data expected in early 2027. The company’s planned trial-in-progress poster at ASCO 2026 signaled early momentum and transparency in this pivotal study assessing safety, pharmacokinetics, and preliminary efficacy.

Innovent’s IBI363 made a striking early clinical impact at ASCO 2026, reporting an impressive 81.8% overall response rate in first-line PD-L1 negative/low advanced NSCLC during Phase 1, coupled with a 100% disease control rate and durable survival benefits. This compelling data propelled the initiation of global Phase 3 trials, including a direct head-to-head comparison with pembrolizumab plus chemotherapy, underscoring IBI363’s potential to redefine frontline lung cancer treatment.

At the same ASCO meeting, BioNTech showcased promising late-stage clinical progress with pumitamig, a PD-L1/VEGF bispecific antibody demonstrating consistent efficacy alongside chemotherapy in the Phase 2/3 ROSETTA Lung-02 trial for non-small cell lung cancer. This advancement is part of BioNTech’s expansive oncology pipeline, which by 2026 encompassed over 25 Phase 2 and 3 trials—including 13 pivotal studies—highlighting the company’s aggressive commitment to advancing PD-1/VEGF bispecific therapies across multiple solid tumor indications.

Ivonescimab's pivotal Phase 3 data, showcased at ASCO 2026 by Summit Therapeutics and Akeso, marked a significant milestone with a 34% reduction in risk of death and a four-month median overall survival extension in advanced squamous NSCLC patients in China. The HARMONi-6 trial results, demonstrating 27.9 months median survival versus 23.7 months for standard PD-1 plus chemotherapy, underscore the bispecific antibody's potential to reshape lung cancer treatment within China and possibly beyond.

Despite the robust survival benefit, investor reactions have been mixed and volatile, reflecting skepticism about the China-only patient population's generalizability. While Summit Therapeutics' stock surged nearly 600% over two years on early promise, it recently dipped 6% post-ASCO amid concerns over valuation, financing, and whether ivonescimab’s efficacy will translate globally. This cautious market sentiment is compounded by heightened short interest, mixed analyst ratings, and the anticipation of global Phase 3 readouts and clearer U.S. regulatory guidance.

The geographic limitation of the HARMONi-6 trial has fueled debate among experts about ivonescimab's broader applicability, with oncologists like Dr. Suresh Ramalingam emphasizing the need for additional Western studies to confirm whether combining PD-1 and VEGF inhibition in a single molecule produces consistent survival benefits across diverse populations. This ongoing scrutiny shapes regulatory positioning and competitive dynamics, as global validation remains critical for ivonescimab’s potential to challenge established PD-1 therapies outside China.

In a landmark move to dominate the PD-1/VEGF bispecific antibody space, Pfizer and Innovent announced a $10.5 billion global collaboration in May 2026, signaling a strategic shift towards leveraging complementary strengths in oncology drug development. Innovent takes the helm in early-stage development across 12 next-generation cancer programs, while Pfizer capitalizes on its global late-stage development and commercialization prowess, supported by a hefty $650 million upfront payment and nearly $10 billion in milestone incentives. This alliance exemplifies how biopharma giants are pooling resources and expertise to accelerate innovation and broaden global reach in the fiercely competitive solid tumor immunotherapy market.

By mid-2026, the race to develop PD-1/VEGF bispecific antibodies has clearly expanded beyond lung cancer, with companies like Summit and Akeso initiating trials in challenging solid tumors such as colorectal cancer. This diversification is partly driven by the impending Keytruda patent expiry in 2029, prompting pharma to explore new indications where these bispecifics might carve out a significant role. However, the representativeness of lung cancer trial data, particularly from Chinese cohorts where ivonescimab’s phase 3 trial enrolled predominantly older male patients (93% male, median age 64), raises concerns about how well these results translate to more demographically diverse Western populations, complicating the path forward.

Industry experts like Souro Chowdhury argue that while lung cancer has been the initial focus, the true therapeutic potential of PD-1/VEGF bispecific antibodies may lie in other solid tumors that are more VEGF-dependent, such as hepatocellular carcinoma and gastric cancers. This perspective underscores a strategic pivot to target cancers where the VEGF pathway plays a more central role, potentially yielding better efficacy outcomes. Chowdhury’s commentary highlights a growing debate within immuno-oncology circles about whether the current lung cancer-centric development approach might be chasing the wrong target, signaling a critical reassessment of tumor prioritization in bispecific antibody pipelines.