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

Phase 2

Active, not recruiting

• Conditions: Advanced Renal Cell Carcinoma
• Interventions: Drug: fruquintinib+sintilimab; Drug: axitinib / everolimus; Drug: fruquintinib

• Registration Number: NCT05522231
• Lead Sponsor: Hutchmed

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-08-16
• Study First Submitted QC: 2022-08-29
• Study First Posted: 2022-08-30
• Study Start: 2022-10-27
• Status Verified: 2025-01
• Primary Completion: 2025-01
• Last Update Submitted: 2025-01-01
• Last Update Posted: 2025-01-03
• Study Completion: 2025-03

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 265

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Investigational arm	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.
Control arm (comparator)	axitinib / everolimus	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.
Fruquintinib monotherapy factorial study	fruquintinib	fruquintinib, 5 mg, QD, PO, 3 weeks on/ 1 week off, 4 weeks/cycle.

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS) in Part I	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
Objective response rate (ORR) in Part II	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

Secondary Outcome Measures

Name	Time	Method
PFS	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
Safety in Part I	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
Quality of life in Part I	Through study completion, assessed up to 20 months.	Quality of life questionnaire analysis in Part I
Safety in Part II	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.
Disease control rate (DCR)	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
ORR	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
Duration of response (DoR)	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 to Response (TTR)	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
OS	Time from date of randomization until the date of death from any cause, assessed up to 20 months.	OS

Trial Locations

Locations (4)

Fudan University Shanghai Cancer Center; 🇨🇳 Shanghai, China

Beijing Chao-Yang Hospital, Capital Medical University; 🇨🇳 Beijing, China

Cancer Hospital Chinese Academy of Medical Sciences; 🇨🇳 Beijing, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, China