NCT06970353

Phase II Trial of Tunlametinib in NRAS-Mutant Advanced Thyroid Cancer

A Prospective, Single-Arm, Open-Label, Single-Center Phase II Exploratory Clinical Study to Evaluate the Efficacy and Safety of Tunlametinib in Subjects With NRAS-Mutant Locally Advanced or Metastatic Thyroid Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial evaluates Tunlametinib (MEK inhibitor) ± PD-1 in NRAS-mutant advanced thyroid cancer. Key Objectives: Assess efficacy (ORR by RECIST v1.1) Evaluate safety profiles Study Design: Single-arm, single-center 4 cohorts based on: * Histology (differentiated vs. poorly/undifferentiated) * Prior therapy status Treatment: * Cohorts 1-2: Tunlametinib monotherapy (12mg BID) * Cohorts 3-4: Tunlametinib + PD-1 (commercially available) Key Procedures: Screening: NRAS testing + full staging (CT/MRI/PET) Monitoring: q3-week labs, q9-week imaging Follow-up: 30-day safety visit + q3-month survival tracking Endpoints: Primary: ORR Secondary: Safety (CTCAE), PFS, DoR Unique Aspects: First study targeting NRAS in thyroid cancer with MEK+PD-1 Includes rare aggressive subtypes (poorly/undifferentiated)

Detailed description

Research Objective: To evaluate the efficacy and safety of Tunlametinib (monotherapy or in combination with PD-1 mAb) in patients with locally advanced or metastatic NRAS-mutant thyroid cancer. Study Endpoints: Primary Endpoint: Objective response rate (ORR) assessed per RECIST v1.1 (sum of partial and complete response rates). Secondary Endpoints: Efficacy: Disease control rate (DCR) Duration of response (DoR) Time to response (TTR) Progression-free survival (PFS) Overall survival (OS), 6-month survival rate, 12-month survival rate Safety: Adverse events (AEs): Type, incidence, severity (graded by NCI-CTCAE v5.0), duration, and relationship to study treatment Study Design: This is a prospective, single-arm, open-label, single-center Phase II exploratory trial evaluating Tunlametinib ± PD-1 mAb in NRAS-mutant thyroid cancer. Study Phases: Screening: ≤28 days prior to enrollment (informed consent to baseline assessments). Treatment: Until disease progression, intolerable toxicity, consent withdrawal, or investigator decision. Follow-up: Safety visit at 30 days (±7) post-treatment. Survival follow-up every 3 months (telephone/medical records). Cohorts \& Treatment: Cohort 1 (n=10): Untreated, radioactive iodine-refractory, differentiated thyroid cancer. Cohort 2 (n=10): Previously treated, radioactive iodine-refractory, differentiated thyroid cancer. Regimen: Tunlametinib 12 mg BID (3-week cycles). Cohort 3 (n=10): Untreated, poorly differentiated/anaplastic thyroid cancer. Cohort 4 (n=10): Previously treated, poorly differentiated/anaplastic thyroid cancer. Regimen: Tunlametinib 12 mg BID + PD-1 mAb(commercially available; per approved labeling). Dose Adjustments: Tunlametinib: Stepwise reduction (12 mg → 9 mg → 6 mg BID) for intolerance. Re-escalation permitted if toxicity resolves (e.g., 6 mg → 9 mg after ≥6 weeks). PD-1: Adjusted per investigator judgment and drug labeling. Efficacy Assessments: Imaging (CT/MRI) every 9 weeks (3 cycles) per RECIST v1.1. Real-time ORR analysis by investigators and sponsor (Shanghai Kezhou Pharmaceutical). Follow-up Procedures: Safety visit: Day 30 (±7) post-treatment (vitals, labs, AE assessment). Survival follow-up: Quarterly until death/loss to follow-up/study termination.

Conditions

• Radioactive Iodine-refractory, Differentiated Thyroid Cancer With NRAS Mutation
• Advanced PDTC or ATC With NRAS Mutation

Interventions

Type	Name	Description
DRUG	Tunlametinib	Locally advanced or metastatic radioactive iodine refractory NRAS mutant differentiated thyroid cancer
DRUG	Tunlametinib+PD-1 mAb	Locally advanced or metastatic NRAS mutant poor-differentiated, undifferentiated thyroid cancer

Timeline

• Start date: 2025-05-27
• Primary completion: 2026-12-30
• Completion: 2031-12-30
• First posted: 2025-05-14
• Last updated: 2025-08-07

Locations

1 site across 1 country: China