Tunlametinib for NRAS‑mutant non‑melanoma refractory solid tumors

An Exploratory, Prospective, Single Arm, Open Label, Single Center, Basket, Phase II Clinical Study of Tunlametinib (HL-085) in Patients With NRAS Mutant Non-melanoma Refractory Solid Tumors

This trial tests tunlametinib to see if it can shrink or control advanced non‑melanoma solid tumors that have NRAS mutations in patients who have failed standard treatments.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tianjin Medical University Second Hospital (other)
• Drugs / interventions: immunotherapy, Tunlametinib
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07170293 on ClinicalTrials.gov

What this trial studies

This is an open‑label, single‑cohort Phase II trial conducted at a single center to observe the efficacy and safety of tunlametinib in patients with advanced, refractory non‑melanoma solid tumors harboring NRAS mutations. The study plans to enroll 15 patients (12 evaluable plus allowance for dropout) based on a target overall response rate of 20% with predefined statistical thresholds. Participants will receive tunlametinib and be followed for tumor response and adverse events using standard oncology assessments. The trial focuses on signal detection in a genetically defined population rather than on comparing against a control arm.

Who should consider this trial

Good fit: Adults with advanced metastatic non‑melanoma solid tumors confirmed to have NRAS mutations who have progressed on or are intolerant to standard therapies and otherwise meet the study's safety criteria are the intended participants.

Not a fit: Patients without NRAS mutations, those with melanoma (excluded from this protocol), people with recent other malignancies within two years, uncontrolled pleural/pericardial/peritoneal effusions, or those who received recent anti‑cancer therapies are unlikely to be eligible or to benefit from this trial.

Why it matters

Potential benefit: If successful, tunlametinib could provide a targeted treatment option that produces tumor shrinkage or disease control for some patients with NRAS‑mutant refractory non‑melanoma solid tumors.

How similar studies have performed: MEK inhibitors have shown clinical activity in NRAS‑mutant melanoma, but evidence in non‑melanoma NRAS‑mutant solid tumors is limited, making this application exploratory.

Eligibility criteria

Exclusion Criteria:

1. Have had other malignant tumors in the past 2 years (excluding tumors with low malignancy such as basal cell carcinoma, squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, etc. that have undergone radical treatment) or have been diagnosed with melanoma;
2. Moderate or greater amounts of pleural effusion, pericardial effusion, and peritoneal effusion that cannot be controlled by researchers (including but not limited to those that require repeated drainage and have clinical symptoms);
3. Prior to initial administration of anti-tumor therapy: Within 4 weeks or 5 drug half lives (whichever is shorter) prior to administration, anti-tumor drugs (including cytotoxic therapy, targeted therapy, antibody therapy, immunotherapy, etc.) were administered; Received nitrosourea or mitomycin C treatment within 6 weeks prior to administration; Received palliative radiotherapy within 2 weeks prior to administration; Received other anti-tumor treatments such as radical radiotherapy and electric field therapy within 4 weeks before administration; Received traditional Chinese medicine treatment for anti-tumor indications within 2 weeks before administration;
4. Toxic reactions of previous anti-tumor treatments that have not yet improved to CTCAE ≤ 1 (excluding hair loss, skin toxicity, or other toxicity that researchers consider to be of no safety risk);
5. Any situation that affects the ingestion of drugs and seriously affects the absorption or pharmacokinetic parameters of the investigational drug, including but not limited to active gastrointestinal ulcers, long-term gastroesophageal reflux disease (GERD), etc;
6. Severe or uncontrollable heart diseases that require treatment, including any of the following conditions (including but not limited to): ECG QT interval prolongation corrected according to the Fridericia formula, male QTcF\>450milliseconds or female QTcF\>470milliseconds; Various clinically significant arrhythmias, including but not limited to second degree type II conduction block, third degree conduction block, etc; Cardiac ultrasound indicates a left ventricular ejection fraction (LVEF) of less than 50%; Within 6 months before the first medication, there is myocardial infarction, unstable angina, NYHA class III or IV heart failure; An arterial/venous thrombosis event occurred within 6 months prior to the first medication, and the risk was deemed uncontrollable, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism; Or known familial and/or acquired thrombophilia tendencies, such as genetic or acquired defects in anticoagulant proteins, coagulation factors, fibrinolytic proteins, etc; 8 Severe or uncontrolled diabetes (fasting blood glucose ≥ 10mmol/L under the standardized blood pressure reduction program), hypertension (poorly controlled under the standardized blood pressure reduction program, systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 100mmHg), epilepsy, chronic obstructive pulmonary disease, interstitial pneumonia, pulmonary fibrosis, Parkinson's disease, active bleeding, systemic active infection;

9\. Any unstable systemic disease (such as severe liver, kidney, or metabolic diseases such as cirrhosis, renal failure, and uremia); Within 14 days or 5 half lives prior to the first administration, have used CYP3A4 potent and moderate inhibitors and inducers, CYP3A4, CYP2C9, and CYP2C8 sensitive substrates, OATP1B1, OATP1B3, OAT1, OAT3, P-gp, and BCRP substrates (see Appendix 8 for details); 11. Cognitive impairment, history of mental illness, other uncontrolled comorbidities, alcohol dependence, hormone dependence, or drug abuse; Received autologous or allogeneic organ or stem cell transplantation surgery within 3 months prior to the first use of medication; Having undergone major surgery or severe trauma within 4 weeks prior to the first use of medication (excluding biopsy due to sample collection); 13. History of immunodeficiency, including HIV antibody positivity or other acquired or congenital immunodeficiency diseases; 14. There are serious eye diseases (excluding cataracts, etc.), and they have not yet recovered and improved to ≤ level 1; The following serological status reflecting active hepatitis B or hepatitis C infection exists: hepatitis B surface antigen positive or hepatitis B core antibody positive, and HBV DNA\>1000 copies/mL; hepatitis C virus antibody positive, and HCV RNA\>the upper limit of normal value; 16 cases of active syphilis infection; 17 is known to be severely allergic to the active ingredients or any excipients of the investigational drug; Participated in other clinical trials within 4 weeks prior to the first administration of medication; 19. Patients with positive pregnancy test results or breastfeeding during the screening period; 20 researchers believe that it is not suitable to participate in this study. According to the researchers' assessment, the patient may have other factors that could affect the research results or lead to the forced termination of this study, such as alcohol abuse, drug abuse, other serious illnesses (including mental illnesses) that require concurrent treatment, serious laboratory test abnormalities, and family or social factors that could affect the patient's safety.

Where this trial is running

Tianjin, Tianjin Municipality

• Tianjin Medical Unversity Second Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Haitao Wang, Ph.D — Tianjin Medical University Second Hospital
• Study coordinator: Haitao Wang, Ph.D

Conditions: Solid Cancers, NRAS, Tunlametinib, MEK