Summit Therapeutics, Daiichi Sankyo and AstraZeneca Launch Clinical Collaboration to Evaluate Ivonescimab and Datroway in Solid Tumors
Summit Therapeutics Inc. (Nasdaq: SMMT) has announced a clinical trial collaboration agreement with Daiichi Sankyo (TSE: 4568) and AstraZeneca (LSE/STO/NYSE: AZN) to investigate the potential of combining ivonescimab with Datroway® (datopotamab deruxtecan) across multiple solid tumor settings. The collaboration is expected to initially focus on breast and lung cancers, with the companies planning to begin with a Phase III clinical trial evaluating the combination as a first-line treatment for patients with triple-negative breast cancer (TNBC).
Ivonescimab is an investigational PD-1/VEGF bispecific antibody being developed by Summit Therapeutics. The company describes the therapy as a novel, potential first-in-class approach designed to simultaneously target the programmed death receptor 1 (PD-1) pathway and vascular endothelial growth factor (VEGF) pathway.
Datroway, meanwhile, is a TROP2-directed antibody-drug conjugate (ADC) developed using Daiichi Sankyo’s proprietary DXd ADC Technology. The product is being jointly developed and commercialized by Daiichi Sankyo and AstraZeneca and forms part of Daiichi Sankyo’s broader oncology pipeline of DXd ADCs.
The new collaboration brings together two distinct therapeutic approaches: an immunotherapy designed to target both PD-1 and VEGF pathways and an ADC designed to deliver a cytotoxic payload to TROP2-expressing cancer cells. Through the planned clinical studies, the companies will investigate whether the combination can provide clinical benefit in multiple solid tumor settings.
The initial focus on first-line TNBC represents an expansion of Summit’s global clinical development program into breast cancer. The companies also intend to evaluate the combination in additional settings over time, including potential applications in lung cancer.
Phase III Trial Planned in First-Line Triple-Negative Breast Cancer
The collaboration is expected to begin with a Phase III clinical trial in patients with previously untreated, or first-line, triple-negative breast cancer. TNBC is a subtype of breast cancer characterized by the absence of three commonly targeted receptors: estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2).
Because TNBC lacks these established molecular targets, treatment strategies frequently rely on chemotherapy, immunotherapy, targeted approaches for eligible patients, and other emerging therapies. The disease can present significant treatment challenges, creating continued interest in therapeutic combinations that may address cancer through complementary biological mechanisms.
The planned Phase III study will examine the combination of ivonescimab and Datroway in this setting. The companies have not disclosed the anticipated enrollment size, trial design, primary endpoint, study sites, or projected initiation date in the announcement.
Beginning development in the first-line setting is strategically significant because treatment decisions made at diagnosis or initial systemic therapy can influence subsequent treatment pathways. A successful combination could potentially establish a new therapeutic approach for patients with TNBC, although its clinical value will ultimately depend on the results of the study and subsequent regulatory review.
The collaboration also provides a framework for investigating the combination beyond breast cancer. Summit said the companies intend to evaluate ivonescimab and Datroway across multiple solid tumor settings, with breast and lung cancer among the areas included in the development plans.
Ivonescimab Combines PD-1 and VEGF Targeting
Ivonescimab is a bispecific antibody designed to engage two biological pathways associated with cancer progression and the immune response: PD-1 and VEGF.
PD-1 is an immune checkpoint receptor expressed on immune cells, including T cells. Tumors can exploit immune checkpoint pathways to suppress immune activity and evade immune surveillance. Drugs that inhibit the PD-1 pathway are an established component of cancer immunotherapy and have been used across a broad range of malignancies.
VEGF, or vascular endothelial growth factor, is involved in the formation and maintenance of blood vessels. Tumors can use angiogenic signaling to support their growth by promoting the development of new blood vessels that supply oxygen and nutrients.
By combining PD-1 and VEGF targeting within a single investigational molecule, ivonescimab is being developed with the goal of addressing both immune checkpoint signaling and tumor-associated angiogenesis. Summit has positioned the therapy as a potential next-generation immunotherapy and is evaluating its use across multiple cancer types.
The company sees the new agreement with Daiichi Sankyo and AstraZeneca as an opportunity to test ivonescimab in combination with an established ADC platform and potentially broaden the range of tumor settings in which the bispecific antibody could be investigated.
Datroway Brings TROP2-Directed ADC Technology
Datroway (datopotamab deruxtecan) is a TROP2-directed antibody-drug conjugate designed to deliver an anticancer payload to tumor cells expressing TROP2.
ADC technology combines the targeting properties of an antibody with a therapeutic payload. The antibody component is designed to recognize a specific antigen associated with cancer cells, while the attached payload is intended to exert an antitumor effect after the ADC reaches its target.
Datroway uses Daiichi Sankyo’s proprietary DXd ADC Technology. It is one of seven DXd ADCs included in Daiichi Sankyo’s oncology pipeline.
The combination of Datroway with ivonescimab therefore brings together two different mechanisms. Datroway is designed to deliver a cytotoxic payload through TROP2 targeting, while ivonescimab is intended to modulate the tumor and immune environment through simultaneous PD-1 and VEGF targeting.
The companies believe this complementary approach warrants clinical investigation across multiple tumor types. The planned trials will determine whether the combination can produce meaningful clinical outcomes and whether its safety and tolerability profile supports continued development.
Companies to Contribute Therapies and Trial Costs
Under the terms of the agreement, Summit Therapeutics, Daiichi Sankyo, and AstraZeneca will each contribute their respective therapies for the planned combination trials. The studies will be sponsored by either AstraZeneca or Daiichi Sankyo.
The companies will also share trial costs, although the announcement does not disclose the specific financial allocation among the three parties.
An important element of the agreement is that each company will retain development and commercial rights to its respective medicine. This structure allows the companies to collaborate on the clinical evaluation of the combination while maintaining their individual rights to the underlying therapies.
For Summit, the arrangement provides access to a major oncology development and commercialization partnership around ivonescimab without transferring ownership of the investigational medicine. For Daiichi Sankyo and AstraZeneca, the collaboration provides an opportunity to explore Datroway in combination with a novel bispecific immunotherapy.
The agreement also allows the companies to leverage complementary scientific and development capabilities as they assess the combination across different tumor types.
Summit Sees Opportunity to Expand Ivonescimab’s Development Program
Maky Zanganeh, Ph.D., President and Co-Chief Executive Officer of Summit Therapeutics, described the collaboration as an important step in the company’s efforts to expand the development of ivonescimab.
“We believe this collaboration with Daiichi Sankyo and AstraZeneca reflects increasing conviction in ivonescimab’s potential as a foundational next-generation immunotherapy and advances our ambition for ivonescimab to become the global PD-1 / VEGF partner of choice for novel combinations,” Zanganeh said.
She added that beginning with a Phase III study in first-line TNBC represents an expansion of Summit’s global development program into breast cancer and could provide a pathway for investigating the combination in additional solid tumor settings.
The comments reflect Summit’s strategy of evaluating ivonescimab not only as an individual therapeutic candidate but also as a potential combination partner for other cancer medicines.
Combination development has become an important area of oncology research because different treatment modalities can potentially address distinct aspects of tumor biology. However, combinations can also introduce additional safety considerations and require clinical studies to establish whether their benefits outweigh the risks.
The planned Phase III trial will therefore provide an important opportunity to generate clinical evidence regarding the combination in first-line TNBC.
Daiichi Sankyo Focuses on Expanding DXd ADC Combinations
John Tsai, MD, Global Head of R&D at Daiichi Sankyo, said the company is focused on maximizing the potential of its DXd antibody-drug conjugate portfolio through innovative combinations and strategic collaborations.
“At Daiichi Sankyo, we are focused on maximizing the potential of our DXd antibody drug conjugate portfolio through innovative combinations and strategic collaborations that support the continued advancement of our pipeline,” Tsai said.
He added that the company is encouraged by the opportunity to investigate ivonescimab in combination with Datroway and its potential to provide clinical benefit to patients.
The collaboration aligns with Daiichi Sankyo’s broader approach to developing ADC-based cancer therapies and exploring their use in combination with other treatment modalities. Datroway represents one component of the company’s broader DXd ADC portfolio, which includes multiple investigational and marketed programs.
Combining ADCs with immunotherapy is an area of active clinical investigation in oncology. The rationale is based on the possibility that targeted delivery of an anticancer payload and modulation of the immune environment could provide complementary effects. The specific clinical benefit of any combination, however, must be established through controlled clinical studies.
AstraZeneca Highlights Immunotherapy and ADC Combination Strategy
AstraZeneca also views the collaboration as part of its broader strategy to investigate combinations that could potentially improve cancer outcomes.
Susan Galbraith, Executive Vice President of Oncology Hematology R&D at AstraZeneca, said the company’s strategy includes combining immunotherapy with ADC approaches to pursue deeper and more durable responses.
“Central to our strategy to transform cancer outcomes is harnessing the power of immunotherapy and antibody drug conjugate combinations to drive deeper, more durable responses,” Galbraith said.
She added that AstraZeneca believes the combination of Datroway and ivonescimab has the potential to make a meaningful difference across multiple tumor types, including lung and breast cancers.
The comments highlight the company’s interest in combining targeted drug delivery technologies with immune-based treatment approaches. The collaboration will provide an opportunity to assess this strategy using Datroway and ivonescimab across several clinical settings.
Potential Expansion Into Lung Cancer
Although the initial trial will focus on first-line TNBC, the broader collaboration is intended to cover multiple solid tumor settings. Lung cancer is among the tumor types the companies expect to explore.
Lung cancer represents a major area of oncology drug development and includes biologically distinct diseases such as non-small cell lung cancer and small cell lung cancer. Immunotherapy and targeted therapies have become important components of treatment for several lung cancer populations, while ADCs are also being investigated across different molecular and clinical settings.
The companies have not yet disclosed the specific lung cancer indications or trial designs that may be pursued under the collaboration. Additional studies will be needed to determine which patient populations could potentially benefit from the combination.
Broader Significance for Oncology Development
The Summit, Daiichi Sankyo, and AstraZeneca collaboration illustrates the increasing focus on combination strategies in cancer drug development. As the number of targeted therapies, immunotherapies, and ADCs continues to grow, pharmaceutical companies are evaluating whether combining medicines with different mechanisms can address multiple biological pathways simultaneously.
In this case, the planned combination brings together PD-1 and VEGF targeting through ivonescimab with TROP2-directed ADC therapy through Datroway.
The approach will now move into clinical evaluation, beginning with a Phase III trial in first-line TNBC. Results from the study will be important in determining whether the combination can demonstrate clinically relevant benefits and support further development.
The collaboration also establishes a broader framework for investigating the combination across additional solid tumors. Each company will contribute its respective medicine and share clinical trial costs, while retaining development and commercial rights to its own therapy.
As the program progresses, future milestones are expected to include trial initiation, patient enrollment, clinical data readouts, and potentially additional studies in other tumor types. Specific timelines and study details have not been provided.
For Summit Therapeutics, the agreement expands ivonescimab’s development program into breast cancer and creates an opportunity to investigate the drug with a commercially established ADC partner. For Daiichi Sankyo and AstraZeneca, the collaboration adds an investigational PD-1/VEGF bispecific antibody to the development strategy for Datroway.
Ultimately, the clinical trials will determine whether the scientific rationale behind the combination translates into improved outcomes for patients. The planned Phase III study in first-line TNBC marks the first major step under the collaboration, while the potential expansion into lung cancer and other solid tumor settings could broaden the scope of the program if supported by clinical evidence.
With each company bringing a distinct therapy, development capability, and oncology expertise to the collaboration, the agreement establishes a multi-company clinical development framework focused on evaluating a new combination approach across several areas of solid tumor treatment.
About Ivonescimab
Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 outside of Summit’s license territories, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. By design, ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.
This design is intended to differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Summit believes ivonescimab’s specifically engineered tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, iScience, 2025).
This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, iScience, 2025) increasing to approximately 10 days at steady state dosing, is to improve upon previously established efficacy thresholds, side effects, and safety profiles associated with prior approved drugs to these targets.
Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently utilized in multiple Phase III clinical trials. Over 5,000 patients have been treated with ivonescimab in clinical studies globally, and over 100,000 patients when considering those treated in a commercial setting in China, as noted by Akeso.
There are currently 16 Phase III clinical studies that are either announced, ongoing, or have been completed studying ivonescimab, five of which are Summit-sponsored global studies, one of which is a multiregional study sponsored by a cooperative group, and 10 of which are being or have been conducted in China by Akeso. Summit began its clinical development of ivonescimab in NSCLC, commencing enrollment in 2023 in two multiregional Phase III clinical trials, HARMONi and HARMONi-3.
In 2025, Summit began enrolling patients in HARMONi-7. Summit expanded its Phase III clinical development program into colorectal cancer (CRC) in the fourth quarter of 2025 by initiating enrollment in HARMONi-GI3. In 2026, Summit announced initiation of HARMONi-GU1, a Phase II/III study in urothelial carcinoma (bladder cancer) with global clinical trial site activations planned to begin by the fourth quarter of 2026.
HARMONi is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who were previously treated with a third-generation EGFR TKI (e.g., osimertinib). Detailed results of the study were provided in September 2025, and a Biologics License Application (BLA) was submitted to the United States Food and Drug Administration (FDA) for marketing authorization, which the FDA accepted for filing in January 2026; the goal Prescription Drug User Fee Act (PDUFA) date is November 14, 2026.
HARMONi-3 is a Phase III clinical trial evaluating ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous or non-squamous NSCLC, irrespective of PD-L1 expression. The clinical trial is evaluating the two histologies as individual, separately powered cohorts with independent statistical powering.
HARMONi-7 is a Phase III clinical trial evaluating ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.
HARMONi-GI3 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with bevacizumab plus chemotherapy in patients with first-line unresectable metastatic CRC.
HARMONi-GU1 is a Phase II/III clinical trial evaluating ivonescimab plus the antibody drug conjugate (ADC) enfortumab vedotin (EV) compared to pembrolizumab plus EV as first-line therapy in patients with previously untreated locally advanced or metastatic urothelial carcinoma (la/mUC).
ILLUMINE is a Phase III study being conducted by GORTEC, a cooperative group dedicated to Head and Neck Oncology, in recurrent / metastatic head and neck squamous cell carcinoma (r/m HNSCC). ILLUMINE is a three-arm Phase III clinical trial designed to evaluate ivonescimab monotherapy, as well as ivonescimab in combination with ligufalimab, Akeso’s proprietary anti-CD47 monoclonal antibody, compared to monotherapy pembrolizumab in patients with PD-L1 positive r/m HNSCC.
Five Phase III ivonescimab clinical trials have read out to date, all five with positive data. Four of these five studies are in NSCLC, and one is in biliary tract cancer (BTC). In addition to Summit’s positive HARMONi study, Akeso has had positive read-outs in three single-region (China), randomized Phase III clinical trials, HARMONi-A, HARMONi-2, and HARMONi-6, for ivonescimab in NSCLC, including a statistically significant overall survival benefit in all three studies from China. Akeso has also reported a statistically significant OS benefit in the single-region (China), randomized Phase III HARMONi-GI1 trial in advanced BTC.
HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.
HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.
HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous NSCLC, irrespective of PD-L1 expression.
HARMONi-GI1 is a Phase III clinical trial evaluating ivonescimab in combination with chemotherapy compared with durvalumab plus chemotherapy as a first-line treatment for patients with advanced BTC.
Akeso is actively conducting additional Phase III clinical studies in settings outside of NSCLC and biliary-tract cancer, including triple-negative breast cancer, head and neck squamous cell carcinoma, small cell lung cancer, colorectal cancer, and pancreatic cancer.
Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was initially approved for marketing authorization in China in May 2024.