Can a malaria drug boost immunotherapy for a tough skin cancer?
NCT ID NCT07750067
First seen Aug 06, 2026 · Last updated Aug 11, 2026 · Updated 3 times
Summary
This phase 2 trial is testing whether adding hydroxychloroquine—a drug commonly used for malaria—to a MEK inhibitor (tunlametinib) and an immunotherapy (pucotenlimab) can improve outcomes for people with advanced NRAS-mutant melanoma. The study aims to see if this combination can shrink tumors and delay progression, while also exploring how autophagy inhibition might make cancer cells more visible to the immune system. Participants must have unresectable or metastatic melanoma with an NRAS mutation.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- A combination of hydroxychloroquine (an autophagy inhibitor), tunlametinib (a MEK inhibitor), and pucotenlimab (an anti-PD-1 antibody)
- What this could lead to
- If successful, this combination could offer a new treatment option for people with advanced NRAS-mutant melanoma, potentially improving tumor shrinkage and delaying progression.
- What could go wrong
- This is a phase 2 trial with a small number of participants, so results may not be conclusive. The combination may cause significant side effects, and the benefit over existing therapies is not yet proven.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
-
Phase 2
Tests whether the treatment actually works, and watches for side effects, in a larger group.
- Participants
-
About 37 people
The number the study aims to enrol. It can still change while the study runs.
- Started
-
Apr 2026
- Expected to finish
-
Jul 2030
An estimate. End dates often move.
- Lead sponsor
-
Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
-
18 years and older
- Sex
-
Anyone
- Healthy volunteers
-
Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * 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). * ECOG, 0-2. * The life expectance should be at least 12 months. * Eligible subjects had not received chemotherapy for locally advanced or metastatic disease and had at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1 criteria). * To ensure eligibility, the following criteria must be met regarding major organ and bone marrow functions: Adequate bone marrow function: absolute neutrophil count (ANC)≥ 1.5\^109/L, platelet count (PLT)≥ 100\^109/L, and hemoglobin level (HB)≥ 9 g/dL (no transfusion received within 14 days). Serum total bilirubin (TBIL) must be ≤ 1.5 times the upper limit of normal (ULN). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the upper limits of normal, serum creatinine ≤1.5, and Creatinine clearance had to be greater than 50 mL/min. Creatinine clearance, as an estimate of glomerular filtration rate (eGFR), was calculated according to the Cockcroft and Gault (C\&G) equation (26): (140 - age \[years\] × weight \[kg\] × 0.85 for male)/ 72\*serum creatinine (μmol/L). The International Normalized Ratio (INR) and activated partial thromboplastin time (aPTT) were a maximum of 1.5 fold the upper limit of normal (This provision applies only to Subjects not receiving anticoagulant therapy; for Subjects receiving anticoagulant therapy, anticoagulation should be within the therapeutic range.). Urine protein ≤ 1+; if urine protein \> 1+, a 24-hour urine collection for protein quantification is required, and the total protein must be ≤ 1 g; FT3, FT4, and TSH levels should be normal, or any abnormalities should be clinically insignificant; lactate dehydrogenase (LDH) ≤ 2 × upper limit of normal (ULN). * A urine pregnancy test must be negative within 7 days before enrollment for women of childbearing potential.Male and female Subjects of reproductive/childbearing potential must use highly effective contraception (e.g., oral contraceptives, IUDs, abstinence, or barrier plus spermicide) during the entire trial and for 12 months after treatment ends. * The subject voluntarily joins the study, has good compliance, and is cooperative with follow-up evaluations. Exclusion Criteria: * 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. * Subjects with a history of other invasive malignancy within the previous 5 years other than nonmelanoma skin cancer were excluded, except for curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, early-stage prostate cancer, and cervical carcinoma in situ. * Subjects who have received hematopoietic growth factors, such as granulocyte colony-stimulating factor (G-CSF), erythropoietin, etc., within 1 week prior to enrollment. * Subjects with positive test results for HIV antibody or Treponema pallidum antibody (based on test results from a Grade A tertiary hospital, including the study center). * Subjects with active hepatitis B or hepatitis C who have not received antiviral therapy: if HBsAg or HBcAb is positive, HBVDNA should be tested (with results above the upper limit of normal range at the research center); if HCV antibody is positive, HCVRNA should be tested (with results above the upper limit of normal range at the research center). * Subjects with known allergy to humanized anti-PD-1 monoclonal antibody drugs and their components; known allergy to MEK inhibitors (e.g., Tunlametinib) and any of their excipients; known allergy to autophagy inhibitors (e.g., hydroxychloroquine) and any of their excipients.
Get updates
Get notified about this study
Sign up to get updates when this study changes or when new studies for Melanoma metastatic are added.
Genom att skicka in godkänner du våra Användarvillkor
Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
-
The places running it
1 site. The list below names each one and where it is.
-
The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
-
A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
-
Sun Yat-sen University
RECRUITINGGuangzhou, Guangdong, 510000, China
More trials for these conditions
Other studies related to the condition(s) this trial covers.
- Could a chicory root fiber supercharge immunotherapy against skin cancer?
- Scientists harness Patients' own immune cells to attack Treatment-Resistant melanoma
- New targeted drug hopes to shrink NRAS-Driven cancers
- Engineered immune cells take on advanced skin and soft tissue cancers
- Could a simple scan replace biopsies for cancer immunotherapy?
- Could one year of immunotherapy be enough for advanced melanoma?