The Illusion of Innovation: Why Bispecific Antibodies Fail to Advance Cancer Therapy

In recent years, the emergence of bispecific antibody therapies—especially those targeting PD-1 and VEGF simultaneously—has been heralded by pharmaceutical companies as a new frontier in oncology. These drugs are marketed as sophisticated, dual-action solutions to the multifaceted nature of cancer. However, a closer look at the actual clinical results reveals a stark disconnect between the promises of complexity and the realities of efficacy.

What the Data Really Shows

Let us begin with the actual outcomes of several prominent bispecific antibody drugs currently in clinical development:

1. Ivonescimab (AK112 / SMT112): A PD-1 + VEGF-A targeting antibody developed by Akeso and Summit Therapeutics. In a Phase I study of 51 patients with multiple advanced solid tumors, it demonstrated an objective response rate (ORR) of just 25.5%, with a disease control rate (DCR) of 63.8%. Grade ≥3 adverse events occurred in 27.5% of patients. Later trials showed PFS improvement over single agents, but no significant improvement in overall survival (OS).

2. AK112 Combined with Chemotherapy: Phase II data in non-small cell lung cancer (NSCLC) showed statistically significant progression-free survival (PFS) benefits compared to chemotherapy alone. However, it failed to demonstrate meaningful overall survival benefits, and toxicity concerns remained.

3. Summit Therapeutics' PD-1/VEGF Bispecific Antibody: Claimed to reduce progression risk by 48% compared to Keytruda in NSCLC, but once again, there was no significant OS improvement.

4. HB0025 / IMM2510 (PD-L1 + VEGF): Currently in early-stage trials, with preclinical evidence suggesting better outcomes than monotherapy combinations. Still, no robust clinical confirmation has been published.

5. GEN1046 (PD-L1 + 4-1BB): Demonstrated a DCR of 65.6% in early trials. Though interesting in terms of mechanism, the design and toxicity profile raise concerns for long-term sustainability.

Despite the variety in molecular targets and formats, a unifying pattern emerges: the benefits remain incremental, often limited to PFS, and rarely (if ever) deliver truly curative outcomes.

A Strategic Critique

My overall assessment of these drugs is simple: they continue the conventional logic of cancer therapy development—that more complex and expensive technology must be inherently better. In reality, bispecific antibodies represent a lateral expansion, stacking targets side by side in hopes of amplifying effect. For pharmaceutical companies, this strategy is highly attractive because it creates a vast array of combinatorial pipeline assets from existing components.

But when compared to the simpler, cheaper approach of dual-drug combination therapies, bispecific antibodies have failed to deliver any substantial improvement. The rationale behind this overengineered class of molecules is commercially clever but therapeutically questionable. I fail to understand the scientific logic when the data does not support meaningful efficacy gains.

🔒 To read the full analysis—including the Five-Factor Evaluation, endpoint critique, and why ClO₂ therapy may outperform bispecifics—please subscribe.