MIAMI, Fla. — October 19, 2026
Summit Therapeutics Inc. (Nasdaq: SMMT) announced the initiation of clinical trial site openings for a global, multiregional Phase II study evaluating ivonescimab, an investigational PD-1/VEGF bispecific antibody, in previously untreated patients with advanced clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer. The randomized, open-label study, designated SMT112-216 / AK112-216 (NCT07877194), is being conducted in collaboration with Summit’s partner, Akeso Inc. The trial plans to enroll approximately 100 patients across clinical sites in the United States and China and will compare ivonescimab alone and in combination with other immunotherapies against an established standard-of-care regimen. The study expands Summit’s clinical development program beyond lung cancer into additional tumor types, including genitourinary malignancies. The company said the trial reflects its strategy to investigate ivonescimab across treatment approaches where significant unmet medical needs remain. Ivonescimab is investigational in Summit’s licensed territories, including the United States and Europe, and its safety and efficacy in advanced ccRCC remain under clinical evaluation.
Four Treatment Arms to Evaluate Ivonescimab-Based Regimens
The Phase II study will evaluate four treatment approaches in patients with incurable, locally advanced or metastatic ccRCC who have not previously received systemic therapy for advanced disease. Participants will be randomized to receive ivonescimab plus cadonilimab, ivonescimab plus ipilimumab, ivonescimab as a single agent, or nivolumab plus ipilimumab as the comparator regimen. Cadonilimab, developed by Akeso, is an investigational bispecific antibody targeting PD-1 and CTLA-4. The trial is designed to assess the safety and efficacy of these treatment approaches, allowing researchers to examine ivonescimab’s potential both as monotherapy and in combination with other immune-based treatments. Summit Chairman and Co-Chief Executive Officer Robert W. Duggan said the study supports the companies’ strategy to explore ivonescimab in multiple treatment settings and tumor types. President and Co-Chief Executive Officer Dr. Maky Zanganeh noted that targeting both PD-1 and VEGF is scientifically relevant in renal cell carcinoma because both pathways are established therapeutic targets in the disease. The study will investigate whether combining these mechanisms within an immuno-oncology treatment strategy may provide clinical benefit in the first-line advanced setting. Results will be needed to establish the comparative efficacy, tolerability and potential role of each regimen.
Dual-Target Mechanism Supports Broader Oncology Development
Ivonescimab, known as SMT112 in Summit’s licensed territories and AK112 in other territories, is designed to combine immune checkpoint inhibition through PD-1 blockade with anti-angiogenic activity through VEGF inhibition in a single bispecific antibody. According to Summit, the molecule’s engineered tetravalent structure contains four binding sites and is designed to enable cooperative binding to its targets, with the potential to preferentially engage the tumor microenvironment. The company is investigating ivonescimab across multiple cancers, including non-small cell lung cancer (NSCLC), colorectal cancer, urothelial carcinoma and other malignancies. Summit’s broader development program includes Phase III studies such as HARMONi, HARMONi-3, HARMONi-7 and HARMONi-GI3, alongside the HARMONi-GU1 program in urothelial carcinoma. The company is also collaborating with Arcus Biosciences on a study evaluating ivonescimab with casdatifan, a HIF-2α inhibitor, in a similar ccRCC setting. According to the company, five Phase III ivonescimab studies have reported positive results to date, including studies in NSCLC and biliary tract cancer. These results form part of the wider clinical development background but do not establish efficacy in ccRCC, which is the focus of the newly initiated Phase II trial..
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Advanced Kidney Cancer Remains a Significant Treatment Challenge
Kidney cancer is among the most commonly diagnosed cancers in the United States, and clear cell renal cell carcinoma accounts for the largest proportion of kidney cancer cases in adults. Summit cited American Cancer Society estimates that approximately 80,450 people in the United States will be diagnosed with kidney cancer in 2026. Although outcomes can be favorable when kidney cancer is detected early, advanced or metastatic disease remains difficult to treat, with the company citing a five-year survival rate of approximately 19% for advanced or late-stage metastatic kidney cancer. Existing treatment approaches include immunotherapy combinations and targeted therapies, underscoring the need to evaluate additional treatment strategies. The SMT112-216 study will investigate whether ivonescimab-based regimens can offer a clinically meaningful option for patients receiving their first systemic treatment for advanced ccRCC. The trial’s multiregional design, collaboration between Summit and Akeso, and evaluation of several treatment approaches are intended to expand understanding of the drug’s potential role in this setting. Ivonescimab was initially approved for marketing in China in May 2024, but it remains investigational in Summit’s licensed territories, including the United States and Europe. The Phase II study’s findings will help determine the next steps for development in advanced kidney cancer.
Source::Summit Therapeutics,,press release
