Efficacy and Safety of Fruquintinib in Combination With Sintilimab in Advanced Renal Cell Carcinoma (FRUSICA-2)

January 1, 2025 updated by: Hutchmed

A Phase II/III Clinical Study to Evaluate the Efficacy and Safety of Fruquintinib in Combination With Sintilimab Versus Axitinib or Everolimus as Second-line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (FRUSICA-2)

The study consists of two parts, the first part is a randomized, open-label, active-controlled study to evaluate the efficacy and safety of fruquintinib in combination with sintilimab versus axitinib or everolimus monotherapy as second-line treatment for locally advanced or metastatic renal cell carcinoma. The second part is a fruquintinib monotherapy factorial cohort study to evaluate the efficacy and safety of fruquintinib monotherapy as for second-line treatment of locally advanced or metastatic renal cell carcinoma.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

The target populations for this study were patients with histologically or cytologically confirmed, locally advanced/ metastatic renal cell carcinoma who progressed during or after or intolerant to previous first-line VEGFR-TKI therapy.

A total of about 249-264 patients are planned to be enrolled in the study, among whom about 234 patients are planned to be enrolled in the first part. The patients who are successfully enrolled will be randomly assigned into the investigational arm or the control arm in a 1:1 ratio. The enrollment of part 2 will be started after that of part 1 is completed. About 15~30 patients are planned to be enrolled in the second part. The patients who are successfully enrolled will receive fruquintinib monotherapy.

Study Type

Interventional

Enrollment (Actual)

265

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Beijing, China
        • Peking University First Hospital
      • Beijing, China
        • Peking University Third Hospital
      • Beijing, China
        • Peking Union Medical College Hospital
      • Beijing, China
        • Cancer Hospital Chinese Academy of Medical Sciences
      • Beijing, China
        • Beijing Chao-Yang Hospital, Capital Medical University
      • Bengbu, China
        • the First Affiliated Hospital of Bengbu Medical College
      • Changchun, China
        • The First Hospital of Jilin University
      • Changsha, China
        • Xiangya Hospital Central South University
      • Changsha, China
        • Hunan Cancer Hospital
      • Chengdu, China
        • Sichuan Provincial People's Hospital
      • Chengdu, China
        • West China Hospital of Sichuan University
      • Chongqing, China
        • Chongqing University Cancer Hospital
      • Fuzhou, China
        • The first affilated hospital of Fujian Medical university
      • Guangzhou, China
        • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
      • Guangzhou, China
        • Sun Yat-sen University Cancer Center
      • Guangzhou, China
        • The First Affiliated Hospital, Sun Yat-sen University
      • Ha'erbin, China
        • Harbin Medical University Cancer Hospital
      • Hangzhou, China
        • The First Affiliated Hospital, Zhejiang University
      • Hefei, China
        • The First Affiliated Hospital of Anhui Medical University
      • Hefei, China
        • Anhui Provincial Hospital
      • Jinan, China
        • Qilu Hospital of Shandong University
      • Jinan, China
        • Shandong Cancer hospital & institute
      • Kunming, China
        • Yunnan Cancer Hospital
      • Lanzhou, China
        • Lanzhou University Second Hospital
      • Nanchang, China
        • The First Affiliated Hospital of Nanchang University
      • Nanjing, China
        • Jiangsu Province Hospital
      • Nanjing, China
        • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
      • Nanjing, China
        • Jiangsu Cancer Hospital
      • Nanning, China
        • Guangxi Medical University Cancer Hospital
      • Nantong, China
        • Nantong Tumor Hospital
      • Qingdao, China
        • The Affiliated Hospital of Qingdao University
      • Shanghai, China
        • Fudan University Shanghai Cancer Center
      • Shanghai, China
        • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
      • Shanghai, China
        • Shanghai General Hospital
      • Shanghai, China
        • Zhongshan Hospital Fudan University
      • Shanghai, China
        • Renji Hospital,Shanghai Jiaotong University School of Medicine
      • Shenyang, China
        • The First Hospital of China Medical University
      • Shenyang, China
        • Liaoning Cancer Hospital & Institution
      • Tianjin, China
        • Tianjin Medical University Cancer Institute & Hospital
      • Tianjin, China
        • The Second Hospital of Tianjin Medical University
      • Wenzhou, China
        • The First Affiliated Hospital of Wenzhou Medical University
      • Wuhan, China
        • Wuhan Union Hospital of China
      • Wuhan, China
        • Tongji Hospital Tongji Medical College Of Hust
      • Xi'an, China
        • The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hosiptal)
      • Xiamen, China
        • The First Affiliated Hospital of Xiamen University
      • Zhengzhou, China
        • Henan Provincial People's Hospital
      • Zhengzhou, China
        • Henan Cancer Hospital
      • Zhengzhou, China
        • The First Affiliated Hospital of Zhengzhou University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. 18 to 75 (inclusive) years of age on the date when ICF was signed;
  2. Histologically or cytologically confirmed renal clear cell carcinoma;
  3. Patients with locally advanced/metastatic renal carcinoma;
  4. Patients with renal carcinoma who progressed during or after or intolerant to previous first-line VEGFR-TKI therapy for advanced/metastatic disease;
  5. At least 1 measurable lesion according to RECIST 1.1;
  6. ECOG PS of 0 or 1;
  7. Adequate organ function.

Exclusion Criteria:

  1. Had previously received therapy targeting immune modulatory receptors or related pathways (including but not limited to therapy targeting PD-1, CTLA-4, IDO, PD-L1, LAG-3, TIGIT, IL-2R and GITR, etc, but excluding related cytokine therapy such as IL2), excluding patients who had received immunotherapy such as anti-PD- (L) 1 antibody in adjuvant/neoadjuvant therapy setting and did not progress within 6 months after discontinuation;
  2. Receiving approved systemic anti-tumor therapy within 2 weeks prior to the first dose;
  3. Toxicities caused by prior anti-tumor therapy before the first dose that did not recover to Grade 0 or 1 per the NCI CTCAE v5.0 or to the level specified in the enrollment criteria (excluding alopecia and peripheral neurotoxicity ≤ CTCAE Grade 2);
  4. Immunosuppression medication within 4 weeks prior to randomization;
  5. Patients with active autoimmune or inflammatory diseases;
  6. Known central nervous system (CNS) metastasis;
  7. History of pneumonitis requiring corticosteroid therapy, or history of or current interstitial lung disease, or current active pulmonary infection, etc.;
  8. Toxicities caused by prior anti-tumor therapy before the first dose that did not recover to Grade 0 or 1 per the National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) v5.0 or to the level specified in the enrollment criteria (excluding alopecia and peripheral neurotoxicities ≤CTCAE Grade 2 caused by platinum-based chemotherapy; thyroid dysfunction with stable disease control after symptomatic treatment);
  9. Human Immunodeficiency Virus (HIV) Infection (HIV 1/2 Antibody positive);
  10. Uncontrolled hypertension despite standard therapy;
  11. Patient with evidence or history of haemorrhagic tendency within 2 months prior to the first dose, regardless of severity.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Investigational arm
fruquintinib, 5 mg, QD, PO, 2 weeks on/1 week off, 3 weeks/cycle; sintilimab, 200 mg, IV infusion, Q3W, 3 weeks/cycle.
Drug: fruquintinib+sintilimab
fruquintinib, 5 mg, QD, PO, 2 weeks on/1 week off, 3 weeks/cycle; sintilimab, 200 mg, IV infusion, Q3W, 3 weeks/cycle.
Other Names:
  • HMPL-013 + IBI308
Active Comparator: Control arm (comparator)
axitinib, 5 mg, twice daily (BID), PO, 3 weeks/cycle, dose escalation will be at the investigator 's discretion ;Everolimus, 10 mg, QD, PO, 3 weeks/cycle.
Drug: axitinib / everolimus
axitinib, 5 mg, twice daily (BID), PO, 3 weeks/cycle, dose escalation will be at the investigator 's discretion based on clinical; everolimus, 10 mg, QD, PO, 3 weeks/cycle.
Other: Fruquintinib monotherapy factorial study
fruquintinib, 5 mg, QD, PO, 3 weeks on/ 1 week off, 4 weeks/cycle.
Drug: fruquintinib
fruquintinib, 5 mg, QD, PO, 3 weeks on/ 1 week off, 4 weeks/cycle.
Other Names:
  • HMPL-013

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS) in Part I
Time Frame: Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
PFS per RECIST 1.1 by BIRC
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Objective response rate (ORR) in Part II
Time Frame: Time from the date of first treatment administration until disease progression or the introduction of a new treatment, assessed up to 20 months.
ORR per RECIST 1.1 by investigator
Time from the date of first treatment administration until disease progression or the introduction of a new treatment, assessed up to 20 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PFS
Time Frame: Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
PFS per RECIST 1.1
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Safety in Part I
Time Frame: Through study completion, assessed up to 20 months.
Severity and Incidence of Adverse event (AEs) and findings in Laboratory test, vital signs, 12-lead Electrocardiogram (ECG), etc. in Part I
Through study completion, assessed up to 20 months.
Safety in Part II
Time Frame: Through study completion, assessed up to 20 months.
Severity and incidence of AEs and findings in such as Laboratory test, vital signs, 12-lead ECG, etc. in Part II.
Through study completion, assessed up to 20 months.
Disease control rate (DCR)
Time Frame: Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
PFS per RECIST 1.1
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
ORR
Time Frame: Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
ORR per RECIST 1.1
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Duration of response (DoR)
Time Frame: Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
DoR per RECIST 1.1
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
Time to Response (TTR)
Time Frame: Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
TTR per RECIST 1.1
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 20 months.
OS
Time Frame: Time from date of randomization until the date of death from any cause, assessed up to 20 months.
OS
Time from date of randomization until the date of death from any cause, assessed up to 20 months.
Quality of life in Part I
Time Frame: Through study completion, assessed up to 20 months.
Quality of life questionnaire analysis in Part I
Through study completion, assessed up to 20 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hutchmed

Investigators

  • Principal Investigator: Dingwei Ye, Fudan University
  • Principal Investigator: Zhi Song He, Peking University First Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 27, 2022

Primary Completion (Estimated)

January 1, 2025

Study Completion (Estimated)

March 1, 2025

Study Registration Dates

First Submitted

August 16, 2022

First Submitted That Met QC Criteria

August 29, 2022

First Posted (Actual)

August 30, 2022

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 1, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2022-013-00CH1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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