Acral MelanomaPhase 2NCT05436990

Antitumor Activity of Vactosertib in Combination With Pembrolizumab in Acral and Mucosal Melanoma Patients Progressed From Prior Immune Check Point Inhibitor

A Phase 2 study testing Pembrolizumab, Vactosertib in people with Acral Melanoma and Mucosal Melanoma, run by Yonsei University at 1 site in South Korea.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This trial is a multicenter, single arm study of efficacy of vactosertib in combination with pembrolizumab in advanced acral or mucosal melanoma patients progressed prior treatment including immunotherapy or targeted therapy and chemotherapy. This trial will be conducted though Korean Cancer Study Group (KCSG). Read more about this study

Who is it for?: Ages 19 years and older
Conditions the study is for: Acral Melanoma, Mucosal Melanoma
What is being tested?: Pembrolizumab, Vactosertib
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteSouth Korea
Study dates: 9 Feb 2023to 10 Mar 2025
Phase: Phase 2
Are there results?: None posted in the registry

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 19 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of acral or mucosal melanoma with stage IV or unresectable stage III diseasewill be enrolled in this study.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention
Have progressed after at least one line of therapy which must include anti-PD-1 (and/or anti-CTLA4) treatment for metastatic melanoma.
patients with actionable BRAF mutation must also have been treated with appropriate targeted therapy (BRAF inhibitor and/or RAF inhibitor),
patient treated with chemotherapy can be enrolled
Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:

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Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1.
c. Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb. Patients must be able to swallow tablets and absorb vactosertib.
Life expectancy > 3 months
Patients with CNS metastasis must have stable neurologic function without evidence of CNS progression within 8 weeks (i.e., patients with controlled, asymptomatic or with resected CNS metastases with no radiological evidence of disease)
Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
Male participants:
A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least [120 days, corresponding to time needed to eliminate any study treatment(s) (e.g. 5 terminal half-lives for pembrolizumab and/or any active comparator/combination) plus an additional 90 days (a spermatogenesis cycle) for study treatments with evidence of genotoxicity at any dose] after the last dose of study treatment and refrain from donating sperm during this period.
Female participants:
A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days 10. A female participant is eligible to participate if she is not pregnant (see Appendix 3), not breastfeeding, and at least one of the following conditions applies: 4. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 120 days (corresponding to time needed to eliminate any study treatments (pembrolizumab and vactosertib) plus 30 days (a menstruation cycle) for study treatments with risk of genotoxicity after the last dose of study treatment.
11. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
12. Have adequate organ function as defined as following. Specimens must be collected within 10 days prior to the start of study intervention.
Absolute neutrophil count (ANC)≥1500/µL
Platelets≥100 000/µL
Hemoglobin≥9.0 g/dL or ≥5.6 mmol/La
Creatinine OR Measured or calculatedb creatinine clearance(GFR can also be used in place of creatinine or CrCl)≤1.5 × ULN OR
≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN
Total bilirubin≤1.5 ×ULN (≤3 × ULN for participants with liver metastases) OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
AST (SGOT) and ALT (SGPT)≤2.5 × ULN (≤5 × ULN for participants with liver metastases)
International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants

Who cannot join

A WOCBP who has a positive urine pregnancy test within 72 hours prior to [randomization/allocation] (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.

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Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Has an active infection requiring systemic therapy.
Concurrent active Hepatitis B (defined as HBsAG positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
Has had an allogenic tissue/solid organ transplant.
Patients treated with co-administration of a strong CYP3A4 inducers (e.g. rifampin, phenytoin, carbamazepine, phenobarbital, and St. John's Wort) or inhibitors (e.g. clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole)
Demonstrates a QTc interval >450 ms for men or >470 ms for women, or has known history of congenital QT-prolongation or Torsade de pointes (TdP).

Trial locations and contacts

1 site in 1 country.

South Korea1 site

Yonsei University Health System, Severance Hospital
Seoul

Other trials in South Korea

About this study

Official title: A Phase II Multicenter Study to Assess the Antitumor Activity of Vactosertib in Combination With Pembrolizumab in Acral and Mucosal Melanoma Patients Progressed From Prior Immune Check Point Inhibitor

Participants will be treated for up to 35 cycles (approximately 2 years) after initiation of treatment with intravenous 200mg of pembrolizumab every 3 weeks in combination with vactosertib. Vactosertib will be given orally for 200mg, bid for 5 days (from Mon. to Fri.) per week. This study will use ORR based on RECIST 1.1 and modified RECIST 1.1 (immune related RECIST) criteria as the primary endpoint and the tumor assessment will be done every 6 weeks. Secondary endpoints are DCR, PFS, OS, and safeties. Exploratory biomarkers predictive biomarker candidates (e.g., level of PD-L1 tumor expression, EMT marker, PD-L1, TGF-β RII, and pSMAD2) in tumor tissue and ctDNA in blood will be investigated in both pre-treatment and post-treatment periods.

Conditions: Acral Melanoma, Mucosal Melanoma
Being tested: Pembrolizumab, Vactosertib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Pembrolizumab, VactosertibDrug
Participants will be treated for up to 35 cycles (approximately 2 years) after initiation of treatment with intravenous 200mg of pembrolizumab every 3 weeks in combination with vactosertib. Vactosertib will be given orally for 200mg, bid for 5 days (from Mon. to Fri.) per week.

Study groups in NCT05436990
Study group	Role	What they receive
vactosertib in combination with pembrolizumab	Experimental	Participants will be treated for up to 35 cycles (approximately 2 years) after initiation of treatment with intravenous 200mg of pembrolizumab every 3 weeks in combination with vactosertib. Vactosertib will be given orally for 200mg, bid for 5 days (from Mon. to Fri.) per week. Receives: Drug: Pembrolizumab, Vactosertib

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Response Rate
Efficacy Analysis Set includes all patients who have received at least 1 dose of the study drug, had measurable disease at baseline according to RECIST 1.1, and had at least 1 post-baseline tumor response assessment. Patients with evidence of disease progression or death before the first scheduled assessment of tumor response will be included in this Analysis Set. It will be the primary analysis set for tumor response.
Primary efficacy endpoints will be based upon investigators' tumor assessments per RECIST 1.1 and will be summarized as follows to evaluate the preliminary anticancer activities of vactosertib and pembrolizumab combination. Overall response rate (ORR) is defined as the proportion of patients who have a partial or complete response to therapy by RECIST 1.1.
Measured: Primary analysis is planned at approximately 6 months after the first dose of last enrolled patient, after study termination, or at study completion decided by Principal Investigator, whichever occurs first, assessed up to 6months.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Feb 202310 Mar 2025

First posted29 Jun 2022
Study start9 Feb 2023
Primary completion10 Mar 2025
Study completion10 Mar 2025

Why it stopped: According to the protocol criteria, during the Phase 1 analysis, the registered participants' imaging evaluation responses did not meet the criteria, leading to an early termination

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Acral MelanomaStudies of the same condition, open and under way.
More trials run by Yonsei 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: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05436990
Sponsor's protocol ID: 4-2022-0713
Status last verified: Mar 2025
First submitted: 16 Jun 2022
Last updated: 2 Apr 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 2
A Study to Evaluate the Efficacy and Safety of IBI363 Monotherapy Compared to Pembrolizumab in Patients With Unresectable Locally Advanced or Metastatic Mucosal or Acral Melanoma Who Had Not Previously Received Systemic Therapy
Melanoma
Active, not recruitingPhase 2
A Study to Compare the Administration of Pembrolizumab After Surgery Versus Administration Both Before and After Surgery for High-Risk Melanoma
Acral Lentiginous Melanoma, Clinical Stage III Cutaneous Melanoma AJCC v8
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
Not yet recruiting
Trial Comparing CPDMA Versus Standard Breadloafing in WLE Specimens of Stage 1-II Cutaneous Melanoma
Cutaneous Melanoma, Stage II, Cutaneous Melanoma
Not yet recruitingPhase 4
A Study of QL1706 Combined With OH2 Injection in Perioperative Treatment of Stage III Resectable Acral Melanoma
Melanoma, Acral Melanoma

All Acral Melanoma trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase II Multicenter Study to Assess the Antitumor Activity of Vactosertib in Combination With Pembrolizumab in Acral and Mucosal Melanoma Patients Progressed From Prior Immune Check Point Inhibitor
ClinicalTrials.gov ID: NCT05436990
Acronym / sponsor ID: 4-2022-0713
Conditions: Acral Melanoma, Mucosal Melanoma
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: According to the protocol criteria, during the Phase 1 analysis, the registered participants' imaging evaluation responses did not meet the criteria, leading to an early termination
Enrolment: 14 participants (actual)
Lead sponsor: Yonsei UniversityUniversity, hospital or other
Study start: 9 Feb 2023 (actual)
Primary completion: 10 Mar 2025 (actual)
Study completion: 10 Mar 2025 (actual)
First posted: 29 Jun 2022 (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.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
vactosertib in combination with pembrolizumab	Experimental	Drug: Pembrolizumab, VactosertibParticipants will be treated for up to 35 cycles (approximately 2 years) after initiation of treatment with intravenous 200mg of pembrolizumab every 3 weeks in combination with vactosertib. Vactosertib will be given orally for 200mg, bid for 5 days (from Mon. to Fri.) per week.

Who may qualify

Ages: 19 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (26 listed)

Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of acral or mucosal melanoma with stage IV or unresectable stage III diseasewill be enrolled in this study.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention
Have progressed after at least one line of therapy which must include anti-PD-1 (and/or anti-CTLA4) treatment for metastatic melanoma.
Participants must have progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
c. Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb. Patients must be able to swallow tablets and absorb vactosertib.

Key exclusion criteria (18 listed)

A WOCBP who has a positive urine pregnancy test within 72 hours prior to [randomization/allocation] (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

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
Pembrolizumab, VactosertibParticipants will be treated for up to 35 cycles (approximately 2 years) after initiation of treatment with intravenous 200mg of pembrolizumab every 3 weeks in combination with vactosertib. Vactosertib will be given orally for 200mg, bid for 5 days (from Mon. to Fri.) per week.	Drug	vactosertib in combination with pembrolizumab

Primary outcome

Overall Response Rate
Time frame: Primary analysis is planned at approximately 6 months after the first dose of last enrolled patient, after study termination, or at study completion decided by Principal Investigator, whichever occurs first, assessed up to 6months.
Efficacy Analysis Set includes all patients who have received at least 1 dose of the study drug, had measurable disease at baseline according to RECIST 1.1, and had at least 1 post-baseline tumor response assessment. Patients with evidence of disease progression or death before the first scheduled assessment of tumor response will be included in this Analysis Set. It will be the primary analysis set for tumor response. Primary efficacy endpoints will be based upon investigators' tumor assessments per RECIST 1.1 and will be summarized as follows to evaluate the preliminary anticancer activities of vactosertib and pembrolizumab combination. Overall response rate (ORR) is defined as the proportion of patients who have a partial or complete response to therapy by RECIST 1.1.

Results and safety

The study was stopped early (reason given: According to the protocol criteria, during the Phase 1 analysis, the registered participants' imaging evaluation responses did not meet the criteria, leading to an early termination). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
Individual participant dataSharing planned: No

Related trials for Acral Melanoma

Active, not recruitingPhase 2
A Study to Evaluate the Efficacy and Safety of IBI363 Monotherapy Compared to Pembrolizumab in Patients With Unresectable Locally Advanced or Metastatic Mucosal or Acral Melanoma Who Had Not Previously Received Systemic Therapy
Melanoma
Active, not recruitingPhase 2
A Study to Compare the Administration of Pembrolizumab After Surgery Versus Administration Both Before and After Surgery for High-Risk Melanoma
Acral Lentiginous Melanoma, Clinical Stage III Cutaneous Melanoma AJCC v8
Active, not recruitingPhase 1/2
A Beta-only IL-2 ImmunoTherapY Study
Advanced Solid Tumor, Unresectable Solid Tumor
Not yet recruiting
Trial Comparing CPDMA Versus Standard Breadloafing in WLE Specimens of Stage 1-II Cutaneous Melanoma
Cutaneous Melanoma, Stage II, Cutaneous Melanoma
Not yet recruitingPhase 4
A Study of QL1706 Combined With OH2 Injection in Perioperative Treatment of Stage III Resectable Acral Melanoma
Melanoma, Acral Melanoma

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. This study is not recruiting at the moment.

Minkyu Jung principal investigator

Division of Medical Oncology, Department of Internal Medicine, Yonsei cancer center, Severance Hospital, Yonsei University Healthy System

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 Pembrolizumab, Vactosertib in people with Acral Melanoma and Mucosal Melanoma, run by Yonsei University at 1 site in South Korea.

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 26 inclusion and 18 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: stopped early, as of the sponsor's last update on 2 Apr 2025. 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 South Korea. 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?

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (time frame: Primary analysis is planned at approximately 6 months after the first dose of last enrolled patient, after study termination, or at study completion decided by Principal Investigator, whichever occurs first, assessed up to 6months.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05436990.

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 2 Apr 2025.