Phase II Study of FCN-159 in NF2 Nerve Sheath Tumors

An Open, Single-Arm Phase II Study Evaluating the Efficacy and Safety of FCN-159 in Selected NF2-associated Nerve Sheath Tumors

The goal of this clinical trial is to evaluate the efficacy and safety of FCN-159 in patients with specific NF2-associated nerve sheath tumors.

Study Overview

• Status: Recruiting
• Conditions: Nerve Sheath Tumor
• Intervention / Treatment: Drug: FCN-159

Detailed Description

1. A phase 2 single arm single center study, total 30 patients will be enrolled;
2. To evaluate the safety and efficacy of FCN-159, a Mek inhibitor, to treat NF2; associated nerve sheath tumors, age≥16, including benign and malignant tumors;
3. Primary endpoint: Objective response rate (ORR)；Secondary Outcome Measures： Clinical benefit rate (CBR)；24w WRS, OS et al..

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ning Li, M.D.; Phone Number: +86 135-5271-5820; Email: yalejiang@cicams.ac.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Shuhang Wang
      • Contact: Shuhang Wang; Phone Number: 13581809307

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥16 years of age, regardless of gender.
2. meet the revised 2022 diagnostic criteria for NF2-associated nerve sheath tumors or pathologically confirmed NF2-associated nerve sheath tumors.
3. should meet one of the following criteria: 1) Incomplete surgical resection, or postoperative recurrence. 2) Systemic therapy is required as determined by the Investigator.
4. the presence of a measurable lesion, as defined by REiNS or RECIST V1.1 criteria.
5. Karnofsky physical status score of ≥70.
6. the patient has adequate organ and bone marrow function.
7. International Normalized Ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN.
8. For patients of childbearing potential: During treatment and for at least 90 days after the last dose, patients should agree to use a highly effective method of contraception.
9. avoid excessive sun exposure and be willing to use an adequate amount of sunscreen in anticipation of sun exposure.
10. be able to understand and voluntarily sign a written informed consent form.

Exclusion Criteria:

• Previously received one of the following treatments:

  1. Pharmaceutical or biological therapy within 3 weeks or 5 half-lives prior to enrollment, whichever is longer.
  2. Use of growth factors that promote platelet, red blood cell, or white blood cell count or function within 7 days prior to enrollment.
  3. Patients who have received major surgery or anti-tumor immunotherapy within 4 weeks prior to enrollment.
  4. Radiation therapy for nerve sheath tumors within 4 weeks prior to enrollment.
  5. Dose adjustment for patients treated with dexamethasone or other corticosteroids within 1 week prior to enrollment.
  6. Patients who have participated in another interventional clinical trial within 4 weeks prior to enrollment.

  7. Prior treatment with Selumetinib or any other MEK 1/2 inhibitor. 2. history of or concurrent with other malignancies. 3. inability to undergo MRI and/or contraindications to MRI. 4. uncontrolled hypertension. 5. the presence of dysphagia, active gastrointestinal disease, malabsorption syndrome, or other condition that interferes with the absorption of the study medication.

     6. previous or current retinal vascular disease. 7. interstitial pneumonitis 8. cardiac function or co-morbidities 9. Immediate family history of sudden cardiac death before age 50. 10.History of any acute neurological condition 11. with active bacterial, fungal or viral infections 12. known hypersensitivity to the study drug, other MEK1/2 inhibitors, or their excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FCN-159; FCN-159 8mg qd po	Drug: FCN-159; FCN-159 8mg qd po

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) estimated by investigators	Investigator-assessed objective mitigation rate ORR (Reponse evaluation in Nerufibromatosis and Schwannomatosis, REiNS criteria and RECIST 1.1 criteria, respectively)	Every 4 cycles (each cycle is 28 days), assessed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical benefit rate (CBR) estimated by investigators	Clinical benefit rate CBR will be assessed by the investigator (REiNS criteria and RECIST 1.1 criteria respectively)	Every 4 cycles (each cycle is 28 days), assessed up to 2 years
24-week word recognition score (WRS)	Hearing response changes will be assessed in patients with hearing impairment (24-week word recognition scores and pure tone audiometry).	up to 24 weeks
pain estimated by NRS	Change in pain intensity score relative to baseline will be assessed according to NRS scale.	Every 4 cycles (each cycle is 28 days), assessed up to 2 years
Duration of response (DOR) assessed by investigator	Duration of response (DoR) is estimated by the investigators as the time from treatment initiation to disease progression or death in patients who achieve complete or partial response, using both RECIST V1.1 and REINS criteria.	From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
progression free survival (PFS) assessed by investigator	PFS is estimated by the investigators as the time from treatment initiation to disease progression or death in patients, using both RECIST V1.1 and REINS criteria.	From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
life quality assessed by NFTI-QOL	Change in quality of life scores relative to baseline will be assessed by Neurofibromatosis type 2 impact on quality of life (NFTI-QOL) score. The higher score means worse life quality.	Every 4 cycles (each cycle is 28 days), assessed up to 2 years
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE 5.0	Adverse events during treatment of FCN-159 will be assessed by the investigators accroding to CTCAE 5.0.	During the intervention

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
• Investigators: Study Director: Shuhang Wang, PhD, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: August 3, 2024
• First Submitted That Met QC Criteria: August 11, 2024
• First Posted (Actual): August 14, 2024

Study Record Updates

• Last Update Posted (Actual): July 29, 2025
• Last Update Submitted That Met QC Criteria: July 25, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: MEK; NF2; nerve sheath tumor
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neuromuscular Diseases; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Peripheral Nervous System Neoplasms; Nerve Sheath Neoplasms
• Other Study ID Numbers: FCN-159-IIT02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: the decision will be made after the primary analysis of results.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No