Innovent and HUTCHMED Jointly Announce that the FRUSICA-2 Phase 2/3 Study of Sintilimab and Fruquintinib Combination Has Met Its Primary Endpoint in Advanced Renal Cell Carcinoma in China
Innovent Biologics (IVBIY) and HUTCHMED have announced positive results from their FRUSICA-2 Phase 2/3 clinical trial, evaluating sintilimab combined with fruquintinib as second-line treatment for advanced renal cell carcinoma (RCC) in China.
The study met its primary endpoint of progression-free survival (PFS) and showed improvements in secondary endpoints, including objective response rate (ORR) and duration of response (DoR). The trial compared the combination therapy against axitinib or everolimus monotherapy for second-line RCC treatment.
The combination has previously received conditional approval from China's NMPA for treating advanced endometrial cancer with pMMR tumors based on the FRUSICA-1 study. The companies plan to proceed with NDA filings in the coming months, aiming to make this treatment option available to patients who have progressed on previous therapy.
Innovent Biologics (IVBIY) e HUTCHMED hanno annunciato risultati positivi dal loro studio clinico FRUSICA-2 di Fase 2/3, che valuta il sintilimab combinato con il fruquintinib come trattamento di seconda linea per il carcinoma renale a cellule chiare (RCC) avanzato in Cina.
Lo studio ha raggiunto il suo obiettivo primario di sopravvivenza libera da progressione (PFS) e ha mostrato miglioramenti negli obiettivi secondari, compresi il tasso di risposta obiettiva (ORR) e la durata della risposta (DoR). La sperimentazione ha confrontato la terapia combinata con l'axitinib o l'everolimus in monoterapia per il trattamento di seconda linea del RCC.
La combinazione ha già ricevuto approvazione condizionata dall'NMPA cinese per il trattamento del cancro endometriale avanzato con tumori pMMR, basata sullo studio FRUSICA-1. Le aziende intendono procedere con le domande NDA nei prossimi mesi, puntando a rendere questa opzione terapeutica disponibile per i pazienti che hanno avuto progressione dopo la terapia precedente.
Innovent Biologics (IVBIY) y HUTCHMED han anunciado resultados positivos de su ensayo clínico FRUSICA-2 de Fase 2/3, que evalúa el sintilimab combinado con fruquintinib como tratamiento de segunda línea para el carcinoma de células renales (RCC) avanzado en China.
El estudio alcanzó su objetivo primario de supervivencia libre de progresión (PFS) y mostró mejoras en los objetivos secundarios, incluyendo la tasa de respuesta objetiva (ORR) y la duración de la respuesta (DoR). El ensayo comparó la terapia combinada con monoterapia de axitinib o everolimus para el tratamiento de segunda línea del RCC.
La combinación ya había recibido aprobación condicional de la NMPA de China para tratar el cáncer endometrial avanzado con tumores pMMR, basado en el estudio FRUSICA-1. Las empresas planean proceder con las solicitudes de NDA en los próximos meses, con el objetivo de hacer que esta opción de tratamiento esté disponible para los pacientes que han progresado en la terapia previa.
Innovent Biologics (IVBIY)와 HUTCHMED는 중국에서 진행된 고급 신장 세포 암(RCC)에 대한 2차 치료제로서 프루퀸티닙과 결합한 신틸리맙의 FRUSICA-2 2/3상 임상 시험에서 긍정적인 결과를 발표했습니다.
이 연구는 무진행 생존 기간(PFS)이라는 주요 목표를 달성했으며, 객관적 반응률(ORR) 및 반응 지속 기간(DoR)과 같은 2차 목표에서도 개선을 보여주었습니다. 이 시험은 2차 RCC 치료를 위해 조합 요법과 악시티닙 또는 에베롤리무스 단독 요법을 비교했습니다.
이 조합은 FRUSICA-1 연구를 기반으로 pMMR 종양이 있는 고급 자궁내막암 치료를 위해 중국 NMPA로부터 조건부 승인을 받았습니다. 두 회사는 향후 몇 달 내에 NDA 제출을 진행할 계획이며, 이전 치료에서 진행된 환자들에게 이 치료 옵션을 제공하는 것을 목표로 하고 있습니다.
Innovent Biologics (IVBIY) et HUTCHMED ont annoncé des résultats positifs de leur essai clinique FRUSICA-2 de Phase 2/3, évaluant le sintilimab associé au fruquintinib comme traitement de deuxième ligne pour le carcinome rénal à cellules claires (RCC) avancé en Chine.
L'étude a atteint son objectif principal de survie sans progression (PFS) et a montré des améliorations dans les critères secondaires, y compris le taux de réponse objective (ORR) et la durée de la réponse (DoR). L'essai a comparé la thérapie combinée à la monothérapie avec axitinib ou everolimus pour le traitement de deuxième ligne du RCC.
La combinaison a déjà reçu une approbation conditionnelle de la NMPA chinoise pour le traitement du cancer endométrial avancé avec des tumeurs pMMR, basé sur l'étude FRUSICA-1. Les entreprises prévoient de procéder aux dépôts de NDA dans les mois à venir, visant à rendre cette option de traitement disponible pour les patients ayant progressé après un traitement antérieur.
Innovent Biologics (IVBIY) und HUTCHMED haben positive Ergebnisse aus ihrer FRUSICA-2 Phase 2/3 klinischen Studie bekannt gegeben, die Sintilimab in Kombination mit Fruquintinib als Zweitlinienbehandlung für fortgeschrittenes Nierenzellkarzinom (RCC) in China bewertet.
Die Studie erreichte ihr primäres Ziel der progressionsfreien Überlebenszeit (PFS) und zeigte Verbesserungen bei den sekundären Endpunkten, einschließlich der objektiven Ansprechrate (ORR) und der Dauer des Ansprechens (DoR). Die Studie verglich die Kombinationstherapie mit der Monotherapie von Axitinib oder Everolimus zur Zweitlinienbehandlung des RCC.
Die Kombination erhielt bereits eine bedingte Genehmigung von der NMPA Chinas zur Behandlung von fortgeschrittenem Endometriumkarzinom mit pMMR-Tumoren, basierend auf der FRUSICA-1-Studie. Die Unternehmen planen, in den kommenden Monaten mit den NDA-Anträgen fortzufahren, um diesen Behandlungsansatz für Patienten verfügbar zu machen, die nach vorheriger Therapie fortgeschritten sind.
- Met primary endpoint (PFS) in Phase 2/3 trial for advanced RCC
- Demonstrated improvements in secondary endpoints (ORR and DoR)
- Previously received conditional approval for endometrial cancer treatment in China
- Advancing toward NDA submissions
- Results to China market only
- Full trial results not yet disclosed
- Requires additional regulatory approvals before commercialization
Insights
The FRUSICA-2 Phase 2/3 trial results represent a significant clinical milestone for Innovent and HUTCHMED's combination therapy. Meeting the primary endpoint of progression-free survival in second-line advanced renal cell carcinoma positions this regimen as a potentially important new treatment option in a difficult-to-treat disease setting.
The study demonstrated statistically significant improvements not only in PFS but also in key secondary endpoints including objective response rate and duration of response, suggesting robust anti-tumor activity. This multi-endpoint success strengthens the clinical value proposition.
Notably, this sintilimab/fruquintinib combination already holds conditional approval in China for advanced endometrial cancer with pMMR tumors, indicating established regulatory precedent and manufacturing infrastructure. This existing approval pathway may potentially streamline the regulatory process for this new indication.
From a clinical perspective, second-line RCC represents a substantial unmet need, as many patients progress after initial therapy. The positive comments from leading investigators at prestigious institutions (Fudan University Cancer Center and Peking University) lend credibility to the findings and suggest potential for clinical adoption if approved.
The companies' statements about proceeding to regulatory submissions suggests confidence in the robustness of the data package. Full data presentation at an upcoming scientific conference will provide critical details on efficacy magnitude, safety profile, and potential competitive positioning against existing second-line treatments.
This positive readout creates meaningful commercial opportunity for Innovent and HUTCHMED in China's renal cell carcinoma market. With approximately 74,000 new RCC cases diagnosed annually in China, the second-line treatment setting represents a substantial addressable market.
The strategic value extends beyond this single indication. This marks the second positive Phase 3 readout for the sintilimab/fruquintinib combination following endometrial cancer, establishing a pattern of clinical success that validates their combination strategy. This approach leverages complementary mechanisms – PD-1 inhibition plus VEGFR inhibition – creating a differentiated market position.
The commercial landscape for second-line RCC in China is less crowded than in Western markets, potentially allowing for significant market penetration if approved. The combination's domestic development also aligns with China's healthcare policies favoring locally-developed innovative therapies.
For Innovent specifically, this represents continued expansion of sintilimab's utility across multiple cancer types, enhancing the product's commercial potential and lifecycle. The partnership with HUTCHMED appears strategically sound, combining complementary assets in a way that maximizes value for both companies.
The companies' plan to advance regulatory communications signals potential commercialization timeline within 12-18 months, depending on review timelines. Investors should watch for the complete data disclosure at scientific conferences to better assess competitive positioning and commercial potential relative to existing standard-of-care treatments in second-line RCC.
The combination of sintilimab and fruquintinib received conditional approval from
The FRUSICA-2 study is a randomized, open-label, active-controlled study to evaluate the efficacy and safety of sintilimab in combination with fruquintinib versus axitinib or everolimus monotherapy for the second-line treatment of advanced RCC (NCT05522231). In addition to the primary endpoint PFS, the combination also demonstrated improvements in secondary endpoints, including objective response rate (ORR) and duration of response (DoR). Full results will be submitted for presentation at an upcoming scientific conference.
Prof Dingwei Ye of Fudan University Shanghai Cancer Center and the co-leading Principal Investigator of the FRUSICA-2 study, said: "The rapid advancements in targeted therapies, immunotherapies, and their combination regimens have led to a significant evolution in the treatment landscape for advanced renal cell carcinoma. Targeted therapy remains an indispensable and crucial component in systemic treatment of advanced RCC in
Prof Zhisong He of Peking University First Hospital and the co-leading Principal Investigator of the FRUSICA-2 study, said: "The positive results from this Phase 3 study of the sintilimab and fruquintinib combination represent a significant advancement in the treatment of advanced renal cell carcinoma. We are optimistic about the clinical implications of the findings as we strive to provide more effective treatment options for patients who may not have had adequate responses to previous therapies."
Dr Hui Zhou, Senior Vice President of Innovent, stated: "We are encouraged by the positive results in the FRUSICA-2 clinical trial. These outcomes not only underscore the great potential of the combination therapy of sintilimab and fruquintinib but also bring new hope to previously treated patients with advanced renal cell carcinoma. We look forward to working closely with HUTCHMED to jointly advance the registrational communication of this innovative combo therapy and make it available to patients as soon as possible."
Dr Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED, stated: "The encouraging results from our study provide clear evidence for the combination of fruquintinib and sintilimab as a viable new treatment option for advanced renal cell carcinoma patients who have progressed on previous therapy. This not only reaffirms our commitment to advancing cancer therapies but also represents an important step forward in addressing unmet medical needs within this patient population. I extend my heartfelt gratitude to the patients and investigators who participated in this research; their contributions have been vital to our success. We look forward to sharing detailed findings with regulatory authorities and progressing toward NDA filings in the coming months."
About Kidney Cancer and RCC
It is estimated that approximately 435,000 new patients were diagnosed with kidney cancer worldwide in 2022.[i] In
About Sintilimab
Sintilimab, marketed as TYVYT® (sintilimab injection) in
In
- For the treatment of relapsed or refractory classic Hodgkin's lymphoma after two lines or later of systemic chemotherapy;
- For the first-line treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
- For the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who progressed after EGFR-TKI therapy;
- For the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
- For the first-line treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
- For the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
- For the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
Furthermore, sintilimab's eighth indication, in combination with fruquintinib for the treatment of patients with advanced endometrial cancer with pMMR tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation, was conditional approved by the NMPA in December 2024. And the NDA for sintilimab in combination with ipilimumab as neoadjuvant treatment for resectable MSI-H/dMMR colon cancer is under the NMPA review and has been granted Priority Review designation.
In addition, three clinical studies of sintilimab have met their primary endpoints:
- Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
- Phase 3 study of sintilimab monotherapy as second-line treatment for squamous non-small cell lung cancer with disease progression following platinum-based chemotherapy;
- Phase 2/3 study of sintilimab in combination with fruquintinib versus axitinib or everolimus monotherapy for the second-line treatment of advanced RCC.
About Fruquintinib
Fruquintinib is a selective oral inhibitor of all three vascular endothelial growth factor (VEGF) receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.[iv]
About Fruquintinib Approvals
Fruquintinib is co-developed and co-marketed in
The combination of ELUNATE® (fruquintinib) and TYVYT® (sintilimab injection) has conditional approval in
Takeda holds the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside mainland
The global regulatory submissions are based on data from two large, randomized, controlled Phase III trials in colorectal cancer, the global, multi-regional FRESCO-2 trial and the FRESCO trial conducted in
The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated:
About Fruquintinib for Second-line Treatment of RCC
The
Results from a proof-of-concept Phase Ib/II study of fruquintinib plus sintilimab were published in Targeted Oncology in January 2025. The combination demonstrated promising efficacy and a tolerable safety profile in this setting. At the data cutoff of October 9, 2024, all 20 enrolled previously treated patients were evaluable for efficacy, with a median follow-up duration of 45.7 months. The confirmed ORR was
About Innovent
Innovent is a leading biopharmaceutical company founded in 2011 with the mission to empower patients worldwide with affordable, high-quality biopharmaceuticals. The company discovers, develops, manufactures and commercializes innovative medicines that target some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has launched 15 products in the market. It has 3 new drug applications under regulatory review, 3 assets in Phase III or pivotal clinical trials and 16 more molecules in early clinical stage. Innovent partners with over 30 global healthcare companies, including Lilly, Sanofi, Incyte, Adimab, LG Chem and MD Anderson Cancer Center.
Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.
Statement:
（1）Innovent does not recommend the use of any unapproved drug (s)/indication (s).
（2）Ramucirumab (Cyramza®) and Selpercatinib (Retsevmo®) and Pirtobrutinib (Jaypirca®) were developed by Eli Lilly and Company.
About HUTCHMED
HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Since inception, HUTCHMED has focused on bringing drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in
Forward-Looking Statements
This news release may contain certain forward-looking statements that are, by their nature, subject to significant risks and uncertainties. The words "anticipate", "believe", "estimate", "expect", "intend" and similar expressions, as they relate to Innovent, are intended to identify certain of such forward-looking statements. Innovent does not intend to update these forward-looking statements regularly.
These forward-looking statements are based on the existing beliefs, assumptions, expectations, estimates, projections and understandings of the management of Innovent with respect to future events at the time these statements are made. These statements are not a guarantee of future developments and are subject to risks, uncertainties and other factors, some of which are beyond Innovent's control and are difficult to predict. Consequently, actual results may differ materially from information contained in the forward-looking statements as a result of future changes or developments in our business, Innovent's competitive environment and political, economic, legal and social conditions.
Reference: |
[i] The Global Cancer Observatory, kidney cancer fact sheet. https://gco.iarc.who.int/media/globocan/factsheets/cancers/29-kidney-fact-sheet.pdf. Accessed February 19, 2025. |
[ii] The Global Cancer Observatory, |
[iii] Wang J, et al. Durable blockade of PD-1 signaling links preclinical efficacy of sintilimab to its clinical benefit. mAbs 2019;11(8): 1443-1451. DOI: 10.1080/19420862.2019.1654303. |
[iv] Sun Q, et al. Discovery of fruquintinib, a potent and highly selective small molecule inhibitor of VEGFR 1, 2, 3 tyrosine kinases for cancer therapy. Cancer Biol Ther. 2014;15(12):1635-45. doi: 10.4161/15384047.2014.964087. |
[v] Dasari NA, et al. Fruquintinib versus placebo in patients with refractory metastatic colorectal cancer (FRESCO‑2): an international, multicentre, randomised, double‑blind, Phase III study. Lancet. 2023;402(10395):41‑53. doi:10.1016/S0140‑6736(23)00772‑9. |
[vi] Li J, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486-2496. doi:10.1001/jama.2018.7855. |
[vii] Xu H, et al. Fruquintinib Plus Sintilimab in Patients with Treatment‑Naïve and Previously Treated Advanced Renal Cell Carcinoma: Results from a Phase Ib/II Clinical Trial. Targeted Oncology. 2025; 20:113–125. doi.org/10.1007/s11523-024-01120-6. |
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FAQ
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