A new clinical collaboration will explore whether combining a TROP2-directed antibody-drug conjugate with a bispecific immunotherapy can expand treatment possibilities across solid tumors.
AstraZeneca and Daiichi Sankyo have entered into a clinical trial collaboration with Summit Therapeutics to evaluate datopotamab deruxtecan in combination with ivonescimab. Announced on October 2, 2026, the agreement covers multiple tumor types, including breast and lung cancers, with plans to begin with a Phase 3 trial in first-line triple-negative breast cancer (TNBC).
The planned program brings together treatments with complementary mechanisms: an antibody-drug conjugate designed to deliver a cytotoxic payload to cancer cells and a bispecific antibody that targets both immune suppression and tumor blood vessel formation.
Why Combine Datopotamab Deruxtecan with Ivonescimab?
Datopotamab deruxtecan targets TROP2, a protein expressed in several solid tumors. Its antibody component is linked to a topoisomerase I inhibitor payload through cleavable linkers, combining tumor targeting with cytotoxic activity.
Ivonescimab combines PD-1 blockade and VEGF inhibition in a single bispecific antibody. These mechanisms bring together an immunotherapy approach with anti-angiogenic activity. Developed by Akeso, ivonescimab is licensed to Summit in major territories outside China. It is approved for certain non-small cell lung cancer settings in China, while a US application in EGFR-mutated NSCLC remains under FDA review.
The scientific rationale is to investigate whether these different approaches can work together to improve treatment outcomes. Clinical trials will need to establish the combination’s efficacy and safety.
First Focus: Triple-Negative Breast Cancer
The companies intend to start with a Phase 3 study in first-line TNBC. AstraZeneca or Daiichi Sankyo will sponsor the planned combination trials, with all three companies contributing to costs and supplying their respective medicines. Each company will retain development and commercial rights to its treatments.
TNBC lacks estrogen receptors, progesterone receptors, and HER2 overexpression, limiting several treatment approaches available for other breast cancer subtypes.
Datopotamab deruxtecan already has a role in this setting. In May 2026, it received US approval for adults with unresectable or metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy. That approval followed the Phase 3 TROPION-Breast02 trial, which demonstrated a five-month improvement in median overall survival versus chemotherapy and a progression-free survival hazard ratio of 0.57.
Those results provide context for developing datopotamab deruxtecan, but they do not establish the benefit of adding ivonescimab. The proposed combination requires its own clinical evidence.
Expanding the Antibody-Drug Conjugate Combination Strategy
Daiichi Sankyo described the collaboration as part of its strategy to advance its antibody-drug conjugate portfolio through novel combinations. For Summit, the planned study represents an expansion of its global ivonescimab development program into breast cancer, with opportunities to investigate additional solid tumor settings.
The announcement follows AstraZeneca’s September 28 agreement to invest $2 billion in Summit Therapeutics, alongside a separate clinical collaboration evaluating ivonescimab with sonesitatug vedotin, a CLDN18.2-directed antibody-drug conjugate, in gastrointestinal cancers. The companies also outlined plans for a broader development program pairing ivonescimab with additional AstraZeneca cancer medicines.
Together, these agreements signal a wider effort to study antibody-drug conjugates alongside PD-1/VEGF bispecific antibodies. For datopotamab deruxtecan and ivonescimab, the next milestone will be translating that rationale into clinical evidence, beginning with the planned first-line TNBC trial.
Read further on OncoDaily: AstraZeneca Puts $2 Billion Behind Summit’s Ivonescimab, Pairing the PD-1/VEGF Bispecific With Its ADC Portfolio
