Summit Therapeutics has announced the initiation and opening of clinical trial sites for SMT112-216 (NCT07877194), a randomized, open-label, multiregional Phase II trial evaluating ivonescimab-based regimens in previously untreated advanced clear cell renal cell carcinoma (ccRCC) with sites active in the United States (US) and China. The study is being conducted in collaboration with Akeso Inc., ivonescimab’s originator.
The trial will assess ivonescimab, a PD-1/VEGF bispecific antibody (BsAb), either as a monotherapy or in two distinct combinatorial regimens, using nivolumab plus ipilimumab as the standard-of-care (SOC) comparator. The announcement describes the study’s launch and design.
Key finding
Summit Therapeutics has opened a global Phase II trial evaluating ivonescimab alone or in combination with cadonilimab or ipilimumab in treatment-naïve advanced ccRCC. No clinical outcomes have been reported at this stage.
Study Design
| Trial | SMT112-216/AK112-216 (NCT07877194) — randomized, open-label, multiregional Phase II |
|---|---|
| Population | Adults with incurable locally advanced or metastatic ccRCC who have not received prior systemic therapy for advanced disease; approximately 100 patients planned |
| Treatment | Four arms: (1) ivonescimab + cadonilimab; (2) ivonescimab + ipilimumab; (3) ivonescimab monotherapy; (4) nivolumab + ipilimumab (SOC) |
| Primary endpoint | Not disclosed in the announcement |
| Key secondary endpoints | Not disclosed in the announcement |
Cadonilimab, used in one of the experimental arms, is an investigational PD-1/CTLA-4 BsAb developed by Akeso. The study is separate from, but complementary to, Summit’s existing clinical trial collaboration with Arcus Biosciences, which is evaluating ivonescimab in combination with casdatifan, a HIF2α inhibitor, in a comparable ccRCC setting.
Results and Safety
SMT112-216 has just opened for enrollment, so no efficacy, safety, or tolerability outcomes were disclosed in the announcement and will not be available until the trial matures.
Clinical Context
Kidney cancer ranks among the top 10 most commonly diagnosed cancers in the US, with an estimated 80,450 new diagnoses projected for 2026, according to the American Cancer Society (ACS). While early-stage kidney cancer carries a favorable prognosis, the five-year survival rate for patients with advanced or metastatic disease is approximately 19%. Current treatment approaches for metastatic ccRCC include immunotherapy-based combinations and targeted therapies, with nivolumab plus ipilimumab representing one established first-line standard. Both the PD-1 and VEGF pathways have demonstrated clinical validity as therapeutic targets in this disease, providing the mechanistic rationale for evaluating ivonescimab’s dual blockade in this setting.
Ivonescimab carries a broad Phase III developmental program spanning non-small cell lung cancer, colorectal cancer, biliary tract cancer, and urothelial carcinoma, totalling five Phase III trials with positive results to date, though none are in ccRCC. A Biologics License Application for ivonescimab in EGFR-mutated NSCLC has been accepted by the US Food and Drug Administration (FDA), with a Prescription Drug User Fee Act (PDUFA) goal date of November 14, 2026. Ivonescimab remains investigational and is not approved by any regulatory authority in Summit’s license territories, including the US and Europe.
Sources
- Summit Therapeutics. “Summit Therapeutics Announces Opening of Global Phase II Study of Ivonescimab-Based Regimens in Advanced Clear Cell Renal Cell Carcinoma.” Press release. 2026. View source.
