Comparing Tunlametinib Capsules and Combination Chemotherapy in Advanced NRAS-mutant Melanoma

NCT06008106 | Recruiting Phase 3

• 1 other identifier: HL-085-301
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multicenter, two-arm, open-label, randomized controlled phase III clinical trial to evaluate the efficacy and safety of tunlametinib capsule in comparison with the combination chemotherapy of investigator's choice in advanced melanoma patients with NRAS mutation who have received immunotherapy before. Subjects were stratified according to the baseline lactate dehydrogenase level and chemotherapy.

Conditions

Melanoma

Keywords

Mitogen-Activated Protein Kinase Kinases; NRAS; Melanoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival(PFS)

  defined as the time from first dose to the earliest documented disease progression or death due to any cause

  up to 12 months

Secondary Outcomes (3)

• Overall survival(OS)

  up to 12 months

• Duration of response(DOR)

  up to 12 months

• Disease control rate(DCR)

  up to 12 months

Study Arms (2)

tunlametinib

EXPERIMENTAL

Drug tunlametinib will be administered as 12mg BID

Drug: tunlametinib

Assigned Interventions

ACTIVE COMPARATOR

combination chemotherapy

Drug: paclitaxel +carboplatin, or temozolomide +cisplatin, or dacarbazine +cisplatin

Interventions

tunlametinib DRUG

12mg BID

tunlametinib

paclitaxel +carboplatin, or temozolomide +cisplatin, or dacarbazine +cisplatin DRUG

according to investigators' suggestion

Assigned Interventions

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age.
• Patients with unresectable stage III or metastatic IV melanoma confirmed by histology or cytology.
• History of immunotherapy failure or could not tolerate immunotherapy
• NRAS mutation at baseline;.
• There is at least one lesion that can be evaluated as target lesions according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
• Eastern cooperative oncology group (ECOG) performance status of grade 0-1.
• Life expectancy \> 3 months.
• No major surgery (excluding baseline tumor biopsy) or major trauma occurred at least 4weeks prior to investigational drug administration.
• Left ventricular ejection fraction (LVEF) ≥ 50% within 7 days before dosing according to echocardiographic findings.
• Able to understand and voluntarily sign the Informed Consent Form.
• Patients must be willing and able to complete the study procedure and follow-up examination.

You may not qualify if:

• Having the following treatment before receiving the study drug: ① received chemotherapy, targeted therapy or other study drug treatment within 4 weeks before the first administration or within 5 half lives of the drug (whichever is longer); ② received immunotherapy and biological therapy within 4 weeks before the first administration; ③ received traditional Chinese medicines with anti-tumor activities approved by National Medical Products Administration (NMPA) within 2 weeks before the first administration.;
• The toxic reactions of previous anti-tumor treatment have not been recovered;
• Current use of other anti-cancer drugs.
• Subjects with symptomatic or untreated brain metastasis, meningeal metastasis or spinal cord compression except for subjects with asymptomatic brain metastasis;
• History of any of the following within 6 months of screening: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass grafting, symptomatic congestive heart failure, severe heart arrhythmia requiring medication, uncontrolled hypertension, cerebrovascular accident, or transient ischemic attack, diabetic ketoacidosis, deep vein thrombosis, or symptomatic pulmonary embolism.
• ECG Corrected Q-T interval formula (QTcB) ≥ 480 msec (adjusted by Bazett's formula) during screening, or a history of congenital long QT syndrome.
• History or current evidence of retinal diseases;
• Previous or current neuromuscular diseases related to CK elevation;
• Previous or current interstitial lung disease or interstitial pneumonitis;
• Uncontrolled concomitant diseases or infectious diseases.
• Bleeding symptoms of grade 3 as defined by the National Cancer Institute General Terminology Standard for Adverse Events (NCI CTCAE V5.0) within the 4 weeks prior to study initiation.
• Inability to swallow the capsule, refractory nausea and vomiting, malabsorption, external biliary diversion, or any small intestinal resection that would preclude adequate absorption of the study drug.
• Patients who are receiving and cannot discontinue regimen-prohibited intravenous or oral drugs that affect CYP isoenzymes (strong inducers and strong inhibitors of CYP2C9) at least 1 week prior to initiation of study treatment and during the study period.
• Patients with a history of malignancy within the past 5 years;
• Human immunodeficiency virus (HIV) antibody positive; syphilis antibody (anti-TP) positive; Hepatitis C virus (HCV) antibody positive and HCV RNA positive; HBsAg positive and HBV DNA positive.

Sponsors & Collaborators

• Shanghai Kechow Pharma, Inc.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

CP protocol

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Hongqi Tian, phD

  Shanghai Kechow Pharma, Inc.

  STUDY DIRECTOR

Central Study Contacts

Lixia Gong, Master

CONTACT

15800569407; gonglx@kechowpharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2023
• First Posted: August 23, 2023
• Study Start: November 2, 2023
• Primary Completion (Estimated): September 22, 2027
• Study Completion (Estimated): September 22, 2027
• Last Updated: June 28, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)