CLINICAL TRIALS PROFILE FOR FRUQUINTINIB

All Clinical Trials for Fruquintinib

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT01645215 ↗	Phase I Study of Fruquintinib(HMPL-013) in Patients With Advanced Solid Tumors	Completed	Fudan University	Phase 1	2011-01-01	Fruquintinib (HMPL-013) is a novel oral small molecule that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts. This first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics , safety and preliminary anti-tumor activity of HMPL-013 at single doses and multiple doses .
NCT01645215 ↗	Phase I Study of Fruquintinib(HMPL-013) in Patients With Advanced Solid Tumors	Completed	Hutchison Medipharma Limited	Phase 1	2011-01-01	Fruquintinib (HMPL-013) is a novel oral small molecule that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts. This first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics , safety and preliminary anti-tumor activity of HMPL-013 at single doses and multiple doses .
NCT01955304 ↗	Food Effect Study of Single Dose of Fruquintinib (HMPL-013) in Healthy Subjects	Completed	Hutchison Medipharma Limited	Phase 1	2012-06-01	This study will determine the effect of food on the pharmacokinetics (PK) of a single dose of 4mg fruquintinib in normal healthy subjects.
NCT01975077 ↗	A Phase Ib Study of Fruquintinib in 3rd Line mCRC	Completed	Fudan University	Phase 1/Phase 2	2012-12-01	Fruquintinib is a novel oral small molecule compound discovered and developed by Hutchison MediPharma that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts.Based on first-in-human study, both 4mg QD and 5mg 3wks on/1wk off are safety and efficacy, this phase Ib study is to evaluable the safety, tolerability and efficacy of these 2 regimens with mCRC failed 2nd therapy or more and to determine the recommended dose and regimen in phase II/III study.
NCT01975077 ↗	A Phase Ib Study of Fruquintinib in 3rd Line mCRC	Completed	Sun Yat-sen University	Phase 1/Phase 2	2012-12-01	Fruquintinib is a novel oral small molecule compound discovered and developed by Hutchison MediPharma that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts.Based on first-in-human study, both 4mg QD and 5mg 3wks on/1wk off are safety and efficacy, this phase Ib study is to evaluable the safety, tolerability and efficacy of these 2 regimens with mCRC failed 2nd therapy or more and to determine the recommended dose and regimen in phase II/III study.
NCT01975077 ↗	A Phase Ib Study of Fruquintinib in 3rd Line mCRC	Completed	Hutchison Medipharma Limited	Phase 1/Phase 2	2012-12-01	Fruquintinib is a novel oral small molecule compound discovered and developed by Hutchison MediPharma that selectively inhibits vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 and has demonstrated potent inhibitory effects on multiple human tumor xenografts.Based on first-in-human study, both 4mg QD and 5mg 3wks on/1wk off are safety and efficacy, this phase Ib study is to evaluable the safety, tolerability and efficacy of these 2 regimens with mCRC failed 2nd therapy or more and to determine the recommended dose and regimen in phase II/III study.
NCT02196688 ↗	Study of Fruquintinib in Patients With Metastatic Colorectal Cancer	Completed	Fudan University	Phase 2	2014-04-01	Fruquintinib administered at 5mg once daily in 4 weeks treatment cycle (three weeks on and one week off) was well tolerated and demonstrated encouraging preliminary clinical antitumor activity in patients with advanced Colorectal Cancer (CRC) in Phase Ib study. This study is aimed to evaluate the efficacy and safety of Fruquintinib in the treatment of patients with metastatic CRC who have progressed after metastatic CRC second line or above standard chemotherapy.

Clinical Trial Conditions for Fruquintinib

Condition Name

Condition Name for Fruquintinib
Intervention	Trials
Metastatic Colorectal Cancer	16
Colorectal Cancer	13
Gastric Cancer	7
Colorectal Neoplasms	4

Condition MeSH

Condition MeSH for Fruquintinib
Intervention	Trials
Colorectal Neoplasms	40
Stomach Neoplasms	10
Adenocarcinoma	8
Carcinoma, Non-Small-Cell Lung	5

Clinical Trial Locations for Fruquintinib

Trials by Country

Trials by Country for Fruquintinib
Location	Trials
China	108
United States	37
Japan	9
Australia	4
Hungary	4

Trials by US State

Trials by US State for Fruquintinib
Location	Trials
California	4
Texas	3
Tennessee	3
Missouri	2
Minnesota	2

Clinical Trial Progress for Fruquintinib

Clinical Trial Phase

Clinical Trial Phase for Fruquintinib
Clinical Trial Phase	Trials
Phase 4	3
Phase 3	3
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for Fruquintinib
Clinical Trial Phase	Trials
Not yet recruiting	35
Recruiting	32
Completed	13

Clinical Trial Sponsors for Fruquintinib

Sponsor Name

Sponsor Name for Fruquintinib
Sponsor	Trials
Hutchison Medipharma Limited	27
Fudan University	16
Sun Yat-sen University	5

Sponsor Type

Sponsor Type for Fruquintinib
Sponsor	Trials
Other	93
Industry	35

Fruquintinib: A Breakthrough in Metastatic Colorectal Cancer Treatment

Introduction

Fruquintinib, a selective oral inhibitor of VEGF receptors (VEGFR)-1, -2, and -3, has marked a significant milestone in the treatment of metastatic colorectal cancer (mCRC). Recently approved by regulatory agencies in several countries, fruquintinib offers new hope for patients who have exhausted other treatment options.

Clinical Trials and Approval

FRESCO and FRESCO-2 Trials

The approval of fruquintinib is based on data from the phase 3 FRESCO and FRESCO-2 trials. The FRESCO-2 trial, a multi-regional study, demonstrated that fruquintinib combined with best supportive care (BSC) significantly improved median overall survival (OS) to 7.4 months compared to 4.8 months for the placebo plus BSC group (HR, 0.662; 95% CI, 0.549-0.800; P < .001)[1][5].

The FRESCO trial, conducted in China, also showed promising results with a median OS of 9.3 months for the fruquintinib plus BSC group versus 6.6 months for the placebo plus BSC group (HR, 0.65; 95% CI, 0.51-0.83; P < .001)[5].

Other Clinical Trials

In addition to the FRESCO trials, fruquintinib is being investigated in other clinical settings. The FRONT study, an ongoing multicenter, open-label, randomized clinical trial, is evaluating fruquintinib as a maintenance therapy after first-line treatment for patients with unresectable right-sided mCRC or RAS-mutant left-sided mCRC. Preliminary results indicate better progression-free survival (PFS) outcomes with acceptable toxicity[4].

Market Approval and Availability

United States

Fruquintinib, marketed under the brand name FRUZAQLA™ by Takeda, received FDA approval in November 2023 for the treatment of adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy[1][5].

China

In China, fruquintinib was approved in September 2018 and is co-marketed by HUTCHMED and Lilly under the brand name ELUNATE®. It has been included in the China National Reimbursement Drug List (NRDL) since January 2020 and has benefited over 80,000 colorectal cancer patients as of mid-2023[2].

Hong Kong

Fruquintinib received marketing approval in Hong Kong in January 2024 for patients with mCRC who have previously received fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy[2].

Market Analysis

Current Market Need

The approval of fruquintinib addresses a critical need for new treatments in mCRC, a disease with limited options and poor outcomes for patients who have undergone multiple lines of therapy. Fruquintinib is the first novel chemotherapy-free treatment option approved in the U.S. in over a decade, regardless of biomarker status[5].

Competitive Landscape

Fruquintinib's entry into the market expands the treatment armamentarium for mCRC, particularly for patients without specific molecular markers like HER2 positivity or BRAF mutations. It offers an oral, chemotherapy-free option that improves survival without compromising quality of life, a significant advantage over existing treatments[1].

Economic Impact

The initial market performance of fruquintinib in the U.S. has been promising, with in-market sales reaching $15.1 million in 2023. The drug's inclusion in reimbursement lists and its potential approval in other regions, such as the European Union and Japan, are expected to further boost its market presence[3].

Projections and Future Milestones

Upcoming Regulatory Milestones

• EMA MAA Review: Completion of the European Medicines Agency's marketing authorization application review is expected in mid-2024.
• PMDA NDA Review: The review by the Japan Pharmaceuticals and Medical Devices Agency is anticipated in late 2024.
• NMPA Registration Filing: A registration filing for second-line endometrial cancer is planned for early 2024.
• Phase II/III Trial Results: Top-line results from a phase II/III registration trial in clear cell renal cell carcinoma (RCC) are expected by the end of 2024[3].

Clinical Trial Pipeline

The ongoing and planned clinical trials, such as the FRONT study and the phase 3 MOUNTAINEER-03 trial, will continue to evaluate fruquintinib's efficacy in various settings and combinations, potentially expanding its indications and patient population[1][4].

Patient and Provider Perspectives

Quality of Life

Fruquintinib's oral formulation and manageable safety profile make it an attractive option for patients who are often fragile and fatigued from previous treatments. It offers a survival benefit without negatively impacting quality of life, a crucial consideration for patients with metastatic disease[5].

Clinical Utility

For healthcare providers, fruquintinib adds a valuable tool to their treatment arsenal, particularly in the third-line setting and beyond. Its selectivity and flexibility for combination therapy make it a promising agent for improving patient outcomes[1].

Key Takeaways

• Fruquintinib is a selective oral inhibitor of VEGFR-1, -2, and -3 approved for the treatment of mCRC in several countries.
• Clinical trials, including FRESCO and FRESCO-2, have demonstrated significant improvements in OS and PFS.
• The drug addresses a critical need for new treatments in mCRC, offering a chemotherapy-free option that improves survival without compromising quality of life.
• Upcoming regulatory milestones and ongoing clinical trials are expected to further expand its market presence and clinical utility.

FAQs

What is fruquintinib and how does it work?

Fruquintinib is a selective oral inhibitor of VEGF receptors (VEGFR)-1, -2, and -3, designed to block tumor angiogenesis by inhibiting these receptors.

Which patients are eligible for fruquintinib treatment?

Fruquintinib is approved for adult patients with mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type and medically appropriate, an anti-EGFR therapy.

What are the key findings from the FRESCO and FRESCO-2 trials?

The trials showed that fruquintinib combined with best supportive care significantly improved median overall survival and progression-free survival compared to placebo plus BSC.

Is fruquintinib available in other countries besides the U.S. and China?

Yes, fruquintinib has received marketing approval in Hong Kong and is under review for approval in the European Union and Japan.

What are the potential future indications for fruquintinib?

Fruquintinib is being investigated for potential use in second-line endometrial cancer and clear cell renal cell carcinoma, with top-line results from these trials expected in the near future.

Sources

1. OncLive: Fruquintinib Approval Highlights Strides Made in mCRC Armamentarium in 2023.
2. Biospace: HUTCHMED Receives ELUNATE® (fruquintinib) Marketing Approval in Hong Kong for Treatment of Metastatic Colorectal Cancer.
3. Biospace: HUTCHMED Reports 2023 Full Year Results and Provides Business Updates.
4. Journal of Clinical Oncology: A multicenter, randomized, open-label clinical trial (the FRONT study).
5. OncLive: FDA Approves Fruquintinib for Metastatic Colorectal Cancer.