Efficacy and Safety Evaluation of VS-101 in Combination With Chemoradiotherapy in Patients With Head and Neck Cancer

A Multi-center, Randomized, Open-label, Parallel-group, Phase 2 Study to Evaluate the Efficacy and Safety of VS-101 in Combination With Chemoradiotherapy (CRT) in Patients With Head and Neck Cancer

This will be a multi-center, randomized, open-label, parallel-group study in adult patients with head and neck cancer.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Cisplatin; Radiation: Radiation; Drug: VS-101

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

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale Cancer Center
      • Contact: Clinical Research Coordinator; Phone Number: 203-228-2385; Email: anna.wu@yale.edu
  • New York
    • Manhattan, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
      • Contact: CRM; Phone Number: +82 1099171335; Email: ynmoon@vspharmtech.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Males or females aged more than 18 years at the time of ICF signing
2. Diagnosed based on position emission tomography (PET), computed tomography (CT), or magnetic resonance imaging (MRI) with pathologically confirmed (histologic or cytological) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx

3. Defined by American Joint Committee on Cancer [AJCC] Guidelines 8th Edition:

   • Oral cavity, hypopharynx, or larynx (independent of p16): Stage III, IVa, IVb per TNM guidelines; or
   • Oropharyngeal p16 negative disease: Stage III, IVa, IVb per TNM guidelines; or
   • Oropharyngeal p16 positive disease: Stage III per TNM guidelines
4. Have measurable disease based on RECIST 1.1
5. Participants with head and neck cancer who have limited to those receiving definitive CRT without surgical excision
6. Participants prescribed standard intensity-modulated radiation therapy (IMRT) with a cumulative planned dose of approximately 70 Gy
7. Participants with Eastern Cooperative Oncology Group (ECOG) Performance Statue (PS) of 0 ~ 2
8. Participants with the status of National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI CTCAE) version 6.0 Grade 2 if stable and not clinically significant, or lower for acute or chronic adverse reaction at the time of screening
9. Participants with an expected survival period of at least 20 weeks
10. Participants who can comply with the requirements of the clinical trial protocol
11. Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

1. Medical History

   1. Patients with a history of prior radiation to the head and neck region which overlap with the planned radiation fields (or cumulative doses exceed the constraints for organs-at-risk [OAR]) or with a known susceptibility to radiation.
   2. Patients with active or uncontrolled or clinically significant medical or psychiatric disorders that, in the investigator's opinion, may interfere with informed consent, adherence, or patient safety. Stable medical or psychiatric conditions under a stable dose regimen are permitted.
   3. Patients with a history of uncontrolled seizure disorder. Patients with a remote history of a single provoked seizure or well-controlled seizures on stable monotherapy may be eligible.
   4. Patients who are unable to swallow the study tablet at the screening visit, unless a nasogastric (NG) tube or percutaneous endoscopic gastrostomy (PEG) tube is already in place for clinically indicated reasons and the patient is clinically stable.

2. Patients who show abnormalities in the following test results at the time of screening:

   1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.5 × upper limit of normal (ULN)
   2. Creatine clearance ≤50 mL/min (using Cockcroft-Gault (C-G) formula)
   3. Absolute neutrophil count (ANC) <1,500/µL
   4. Platelets <100,000/µL
   5. Hemoglobin <9 g/dL
   6. Serum calcium >1.5 × ULN
   7. Total bilirubin > 2 × ULN
   8. Prothrombin time (PT) (International Normalized Ratio [INR]) >1.5 × ULN or activated partial thromboplastin time (aPTT) (sec)
   9. Positive result for serum tests (hepatitis B or C virus, human immunodeficiency virus [HIV], rapid plasma reagin [RPR] test)
   10. Patients who show significant abnormalities in electrocardiogram (ECG) test results (e.g.,QTcF > 450 msec)
3. Patients who received hypofractionated chemoradiation regimens (> 2 Gy per day) Note：If it is established that the abnormal lab values are a consequence of their underlying malignant disease rather than any other co-existing condition, reflect minor variations attributable to individual differences or testing conditions, and is not considered clinically significant, the Principal Investigator (PI) may discuss the case with the Medical Monitor to determine eligibility.
4. Patients with known hypersensitivity to components or excipients of clinical investigational drugs
5. Participants with a history of drug addiction within 3 months before ICF signing, unless a Urine drug screen negative result is obtained prior to randomization

6. Contraindicated Drugs and Treatments:

   1. Participants who have administered strong cytochrome P450 (CYP) 3A4 or CYP2D6 inducers or inhibitors within 14 days of baseline or 5 times the drug's half-life, whichever is longer.
   2. Participants who received chemotherapy within 14 days of baseline (drugs or treatment known to have anticancer effects such as cytotoxic chemotherapy, antihormonal therapy, and targeted therapy).
   3. Participants who required intravenous antibiotics, antivirals, or antifungals for active or uncontrolled infection at baseline.
   4. Participants who have administered benzodiazepines (e.g., lorazepam) that causes clinically significant sedation (stable low dose is permitted).
   5. Participants who participated in another clinical trial within 4 weeks of the baseline and administered the clinical trial drug
7. Participants and their spouses (or partners) with childbearing potential who are not using medically acceptable methods of contraception for the duration of the trial and for 14 months (in female participants) and 11 months (in male participants) after the last dose of cisplatin treatment
8. Participants who, in the judgment of other investigators, are not suitable to participate in the study"

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 2 mg of VS-101 + CRT	Drug: Cisplatin; Cisplatin; Radiation: Radiation; Radiation; Drug: VS-101; VS-101
Experimental: 5 mg of VS-101 + CRT	Drug: Cisplatin; Cisplatin; Radiation: Radiation; Radiation; Drug: VS-101; VS-101
Placebo Comparator: Only CRT	Drug: Cisplatin; Cisplatin; Radiation: Radiation; Radiation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	The proportion of participants who achieve an ORR at 6 months and 12 months will be summarized with the 95% confidence interval on the mITT and PP samples.	6 months and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	proportion of subjects who have a complete response (CR), partial response (PR), or stable disease (SD) at 6 months and 12 months will be summarized with the 95% confidence interval on the mITT and PP samples.	6 months and 12 months
Best overall response (BOR)	The BOR will be based on all post-baseline disease assessments that occur prior to the initiation of subsequent anticancer therapy. BOR will be summarized for the following categories: CR, PR, SD, PD and non-evaluable.	6 months and 12 months
Progression-free survival (PFS)	The PFS will be analyzed using Kaplan-Meier methods on the mITT and PP samples. KM estimates and associated two-sided 95% confidence intervals will be presented for each cohort. Participants who have no documented progression and are still alive at the time of analysis will be censored at the time of the latest date of assessment.	At 6 month and 1 year
Locoregional control (LRC)	Rate of Locoregional recurrence after end of treatment (FDG-PET/CT scan).	At 6 month and 1 year
Distant metastasis (DM)	The proportion of participants who develop DM will be summarized with the 95% confidence interval on the mITT and PP samples	through study completion, at most 1 year
Overall survival (OS)	The OS will be analyzed using Kaplan-Meier methods on the mITT and PP samples. KM estimates and associated two-sided 95% confidence intervals will be presented for each cohort, and 1-year survival estimate will be calculated	1 year
Changes in tumor size	Tumor imaging (CT and MRI) will be performed.	through study completion, at most 1 year
Number and severity of treatment-emergent adverse events (TEAEs), treatment-related AEs, and serious adverse events (SAEs) for all dose groups according to the NCICTCAE version 5.0	AE will be measured by Common Terminology Criteria for Adverse Events (CTCAE) v5.0	through study completion, at most of 1 year
Health-related quality of life (HR-QoL)	FACT-H&N V4.; Physical Well-Being; Social/Familiy Well-Being; Emotional Well-Being; Functinal Well-Being	at week1, week8, week11, week 19, week 27 and week 52

Collaborators and Investigators

• Sponsor: VSPharmTech Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: April 16, 2025
• First Submitted That Met QC Criteria: April 27, 2025
• First Posted (Actual): May 6, 2025

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 17, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Physical Phenomena; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Cisplatin; Radiation
• Other Study ID Numbers: VS-101-C3

Drug and device information, study documents

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