Phase II Trial of Tunlametinib in Patients With NRAS Mutant Non-melanoma Refractory Solid Tumors

NCT07170293 | Recruiting Phase 2

• 1 other identifier: PAN-CANCER-NRAS-HL-085
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single cohort, open label exploratory clinical trial aimed at observing and evaluating the efficacy and safety of Tunlametinib (HL-085) in the treatment of refractory solid tumors with advanced metastatic non melanoma. It is expected that the ORR of Tunlametinib (HL-085) treatment can reach 20%. According to the literature results, the experimental group rate is 0.2 and the target value rate is 0.02. If the bilateral alpha is 0.05 and the beta is 0.2, the sample size is calculated as 12 cases in the experimental group. Considering a 20% dropout rate, a total of 15 cases are required.

Conditions

Solid Cancers

Keywords

NRAS; Tunlametinib; MEK

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective Response Rate (ORR) assessed according to the evaluation criteria for the efficacy of solid tumors (RECIST v1.1).

  Up to approximately 24 months.

Secondary Outcomes (5)

• Progression Free Survival(PFS)

  From treatment administration up to a maximum duration of 24 months.

• Duration of Response(DOR)

  Time Frame: Through study completion, an expected average of 24 months

• Disease Control Rate (DCR)

  From treatment administration up to a maximum duration of 18 months

• Overall Survival(OS)

  From treatment administration up to a maximum duration of 24 months.

• Percentage of Participants With Adverse Events (AEs)

  Up to approximately 24 months.

Study Arms (1)

Tunlametinib (HL-085)

EXPERIMENTAL

Patients with NRAS Mutant Non-melanoma Refractory Solid Tumors.

Drug: Tunlametinib

Interventions

Tunlametinib DRUG

Do not chew, dissolve or open the capsule. If you miss a dose of medication, you can take the missed dose 8 hours before the next dose. If the time until the next medication is less than 8 hours, it is not recommended to take it again. Every 21 days for one cycle, subjects will use the investigational drug until the treatment termination criteria specified in the protocol are met. The recommended dosage for the first dose reduction is 9mg, twice daily. The recommended second dose reduction is 6mg, twice daily.

Tunlametinib (HL-085)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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;
• 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);
• 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;
• 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);
• 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;
• 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;
• \. 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.

Sponsors & Collaborators

• Tianjin Medical University Second Hospital: lead

Study Sites (1)

Tianjin Medical Unversity Second Hospital

Tianjin, Tianjin Municipality, 300211, China

RECRUITING

Study Officials

• Haitao Wang, Ph.D

  Tianjin Medical University Second Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Haitao Wang, Ph.D

CONTACT

+86-022-88326610; peterrock2000@126.com

Jinhuan Wang, Ph.D

CONTACT

+86-022-88326385; wjhhappy2008@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2025
• First Posted: September 12, 2025
• Study Start (Estimated): August 31, 2027
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: September 12, 2025

Record last verified: 2025-09

Locations

CN (1)