Tunlametinib in Combination With Pucotenlimab and Hydroxychloroquine in NRAS Mutant Melanoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorSun Yat-sen University
About this trial
This study evaluates the combination of the autophagy inhibitor hydroxychloroquine (HCQ), the MEK inhibitor tunlametinib, and the anti-PD-1 antibody pucotenlimab in patients with locally advanced or metastatic melanoma. The primary objectives are to assess the objective response rate (ORR) and progression-free survival (PFS). Secondary objectives include evaluating adverse events (type, severity, and incidence), duration of response (DOR), disease control rate (DCR), and overall survival (OS), as well as exploring the molecular mechanisms by which autophagy modulation enhances immunogenicity in mutant melanoma. Further exploratory analyses will examine the mechanisms by which autophagy inhibition enhances tumor sensitivity to PD-1 blockade, thereby establishing experimental and theoretical grounds for refining future clinical approaches.
Eligibility criteria
Qualifiers
Age ≥ 18 years of age, both genders.
Subjects with unresectable or metastatic melanoma (Stage III/IV) confirmed by histology or cytology
The mutated NRAS genes were confirmed by sequencing.
Prior systemic antineoplastic therapy is allowed. All acute toxic effects of prior antitumor therapy must have resolved to grade 1 or lower before the start of the study drug, with the exception of alopecia (grade 1 or 2 permitted), neurotoxicity (grade 1 or 2 permitted), or bone marrow parameters (grade 1, 2, or 3 permitted).
Disqualifiers
Subjects who have previously received anti-PD-1 antibody, anti-PD-L1/PD-L2 antibody therapy, and/or VEGFR TKI therapy.
Subjects currently receiving systemic anti-tumor therapy.
Subjects who have participated in or are currently participating in other drug/therapy clinical trials within 4 weeks prior to enrollment (calculated from the date of the last dose of the previous trial).
Subjects who have undergone major surgery within 4 weeks prior to enrollment, or have not recovered from surgical side effects, or have received live vaccination within 4 weeks prior to enrollment.
Trial design
Treatments tested in this trial
- Tunlametinib
- Pucotenlimab
- Hydroxychloroquine (HC)
Treatment groups
37 Participants
are divided into 1 treatment groupSponsors and collaborators
Source ClinicalTrials.gov