Melanoma MetastaticPhase 2NCT07750067
Tunlametinib in Combination With Pucotenlimab and Hydroxychloroquine in NRAS Mutant Melanoma
A Phase 2 study testing Tunlametinib, Pucotenlimab and Hydroxychloroquine (HC) in people with Melanoma Metastatic and NRAS Mutation, run by Sun Yat-sen University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Metastatic, NRAS Mutation
- What is being tested?
- Tunlametinib, Pucotenlimab and Hydroxychloroquine (HC)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2026to 28 Jul 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University
Guangzhou, Guangdong, 510000
Rong cheng Zhang MD, PhD, +86 19898802339 ext. +86 020-873439, zhangrc@sysucc.org.cn
Dandan Li MD, PhD, +86 13570573356, lidd@sysucc.org.cn
About this study
Official title: Enhancing Immunogenicity in NRAS-Mutant Melanoma Via Autophagy Modulation: A Clinical and Mechanistic Study.
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.
- Conditions
- Melanoma Metastatic, NRAS Mutation
- Being tested
- Tunlametinib, Pucotenlimab, Hydroxychloroquine (HC)
- Keywords
- Tunlametinib, Pucotenlimab, Hydroxychloroquine, NRAS mutation, melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TunlametinibDrug
Tunlametinib (3 mg/tablet):
The recommended dose is 12 mg (4 tablets) orally twice daily (approximately every 12 hours), with or without food. Capsules must not be chewed, dissolved, or opened. If a dose is missed, it may be taken up to 8 hours before the next scheduled dose; if the missed dose is discovered within 8 hours of the next dose, it should be skipped.
PucotenlimabDrug
PD-1 antibody (pucotenlimab):
Administered via intravenous infusion over at least 60 minutes, using an in-line filter (0.2-5 μm). The drug is diluted with normal saline prior to infusion. One treatment cycle is defined as 3 weeks (21 days).
Hydroxychloroquine (HC)Drug
Hydroxychloroquine (0.1 g/tablet):
Administered orally at 2 tablets (0.2 g) twice daily, to be taken with meals or milk. Each treatment course consists of 4 consecutive weeks of administration, i.e., 30 days per course.
| Study group | Role | What they receive |
|---|---|---|
| Tunlametinib + Pucotenlimab + Hydroxychloroquine | Experimental | PD-1 antibody (pucotenlimab):
Administered via intravenous infusion over at least 60 minutes, using an in-line filter (0.2-5 μm). The drug is diluted with normal saline prior to infusion. One treatment cycle is defined as 3 weeks (21 days).
Tunlametinib (3 mg/tablet):
The recommended dose is 12 mg (4 tablets) orally twice daily (approximately every 12 hours), with or without food. Capsules must not be chewed, dissolved, or opened. If a dose is missed, it may be taken up to 8 hours before the next scheduled dose; if the missed dose is discovered within 8 hours of the next dose, it should be skipped.
Hydroxychloroquine (0.1 g/tablet):
Administered orally at 2 tablets (0.2 g) twice daily, to be taken with meals or milk. Each treatment course consists of 4 consecutive weeks of administration, i.e., 30 days per course.
Treatment discontinuation criteria:
Patients were permitted to continue treatment until disease progression or development of unacceptable toxicity. Receives: Drug: Tunlametinib; Drug: Pucotenlimab; Drug: Hydroxychloroquine (HC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Defined as the percentage of subjects achieving complete response (CR) or partial response (PR) as assessed by RECIST 1.1.
Measured: up to 180 days
Progression Free Survival (PFS)
Defined as the time from randomization to the date of first documentation of from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.
Measured: up to 180 days
Secondary outcomes (3)
Disease Control Rate (DCR)
DCR was defined as the proportion of CR+PR+SD subjects to total subjects
Measured: up to 180 days
Duration of Response (DoR)
DoR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death.
Measured: up to 180 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
The safety profile will be characterized by reporting the number and percentage of participants (with 95% Clopper-Pearson confidence intervals) for the following endpoints: overall TEAEs, Grade ≥3 TEAEs, serious adverse events (SAEs), treatment-related AEs, AEs leading to permanent drug discontinuation, and AEs leading to dose modification. All AEs will be graded per CTCAE v4.0, and causality will be determined by the investigator.
Measured: 30 days (average of 3 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2026
- Study start1 Apr 2026
- Primary completion28 Jul 2030 (estimated)
- Study completion28 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma MetastaticStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rongcheng Zhang, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07750067
- Sponsor's protocol ID
- B2025-297-01
- Status last verified
- Jul 2026
- First submitted
- 2 Aug 2026
- Last updated
- 10 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Enhancing Immunogenicity in NRAS-Mutant Melanoma Via Autophagy Modulation: A Clinical and Mechanistic Study.
- ClinicalTrials.gov ID
- NCT07750067
- Acronym / sponsor ID
- B2025-297-01
- Conditions
- Melanoma Metastatic, NRAS Mutation
- Keywords
- Tunlametinib, Pucotenlimab, Hydroxychloroquine, NRAS mutation, melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 1 Apr 2026 (actual)
- Primary completion
- 28 Jul 2030 (estimated)
- Study completion
- 28 Jul 2030 (estimated)
- First posted
- 6 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tunlametinib + Pucotenlimab + Hydroxychloroquine | Experimental | Drug: Tunlametinib, Drug: Pucotenlimab, Drug: Hydroxychloroquine (HC)PD-1 antibody (pucotenlimab): Administered via intravenous infusion over at least 60 minutes, using an in-line filter (0.2-5 μm). The drug is diluted with normal saline prior to infusion. One treatment cycle is defined as 3 weeks (21 days). Tunlametinib (3 mg/tablet): The recommended dose is 12 mg (4 tablets) orally twice daily (approximately every 12 hours), with or without food. Capsules must not be chewed, dissolved, or opened. If a dose is missed, it may be taken up to 8 hours before the next scheduled dose; if the missed dose is discovered within 8 hours of the next dose, it should be skipped. Hydroxychloroquine (0.1 g/tablet): Administered orally at 2 tablets (0.2 g) twice daily, to be taken with meals or milk. Each treatment course consists of 4 consecutive weeks of administration, i.e., 30 days per course. Treatment discontinuation criteria: Patients were permitted to continue treatment until disease progression or development of unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TunlametinibTunlametinib (3 mg/tablet): The recommended dose is 12 mg (4 tablets) orally twice daily (approximately every 12 hours), with or without food. Capsules must not be chewed, dissolved, or opened. If a dose is missed, it may be taken up to 8 hours before the next scheduled dose; if the missed dose is discovered within 8 hours of the next dose, it should be skipped. | Drug | Tunlametinib + Pucotenlimab + Hydroxychloroquine |
| PucotenlimabPD-1 antibody (pucotenlimab): Administered via intravenous infusion over at least 60 minutes, using an in-line filter (0.2-5 μm). The drug is diluted with normal saline prior to infusion. One treatment cycle is defined as 3 weeks (21 days). | Drug | Tunlametinib + Pucotenlimab + Hydroxychloroquine |
| Hydroxychloroquine (HC)Hydroxychloroquine (0.1 g/tablet): Administered orally at 2 tablets (0.2 g) twice daily, to be taken with meals or milk. Each treatment course consists of 4 consecutive weeks of administration, i.e., 30 days per course. | Drug | Tunlametinib + Pucotenlimab + Hydroxychloroquine |
Primary outcome
Objective Response Rate (ORR)
Time frame: up to 180 days
Defined as the percentage of subjects achieving complete response (CR) or partial response (PR) as assessed by RECIST 1.1.
Progression Free Survival (PFS)
Time frame: up to 180 days
Defined as the time from randomization to the date of first documentation of from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.
3 secondary outcomes
Disease Control Rate (DCR)
Time frame: up to 180 days
Duration of Response (DoR)
Time frame: up to 180 days
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 30 days (average of 3 months).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tunlametinib, Pucotenlimab and Hydroxychloroquine (HC) in people with Melanoma Metastatic and NRAS Mutation, run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rong cheng Zhang MD, PhD (+86 19898802339 ext. +86 020-873439, zhangrc@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: up to 180 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2026.