Unresectable or Metastatic MelanomaPhase 1/2NCT07817901
Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Combination Therapy With Pembrolizumab and Irinotecan in Patients With Metastatic or Recurrent Malignant Melanoma
A Phase 1/2 study testing Pembrolizumab and Irinotecan in people with Unresectable or Metastatic Melanoma, run by Yonsei University.
Trial summary
This is a single-center, open-label, single-arm Phase 1b/2 clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of pembrolizumab in combination with irinotecan in patients with metastatic melanoma who have relapsed at least 6 months after completion of adjuvant pembrolizumab therapy… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Unresectable or Metastatic Melanoma
- What is being tested?
- Pembrolizumab and Irinotecan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- No sites listed yet
- Study dates
- 1 Nov 2026to 8 Jun 2028
- Phase
- Phase 1/2
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with histologically confirmed non-uveal melanoma, diagnosed as Stage IV or unresectable Stage III melanoma.
- Age ≥19 years at the time of signing the informed consent form.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Patients must be treatment-naïve in the metastatic or unresectable setting (first-line setting) and meet at least one of the following criteria:
- No prior systemic therapy in the metastatic or unresectable setting. B. Patients who previously received pembrolizumab or other immune checkpoint inhibitors (ICIs) as adjuvant therapy, and subsequently experienced relapse or metastasis ≥6 months (180 days) after the last dose, provided that no additional systemic therapy was administered after recurrence in the metastatic setting.
- Patients with CNS metastases must have stable neurological function without evidence of CNS progression within 4 weeks prior to enrollment (i.e., treated/controlled or asymptomatic CNS metastases, or resected CNS metastases without radiographic evidence of disease).
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- Female subjects of childbearing potential must have a negative serum or urine pregnancy test during the screening period. If the urine test result is positive or inconclusive, a serum pregnancy test must be performed.
- Patients must have measurable disease per RECIST v1.1 (lesions previously irradiated may be considered measurable if disease progression at the site is documented).
- Adequate organ function as defined below:
- Table 2. Organ Function Requirements Hematological Absolute neutrophil count (ANC) ≥1,500/μL Platelets ≥100,000/μL Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L Renal Serum creatinine ≤1.5 × ULN or If creatinine >1.5 × ULN: creatinine clearance (CrCl) ≥40 mL/min (GFR may be used in place of creatinine or CrCl) Hepatic Total bilirubin ≤1.5 × ULN or If total bilirubin >1.5 × ULN: direct bilirubin ≤ ULN (Exception: Gilbert's syndrome - total bilirubin <3 × ULN and ALT <3 × ULN) AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN in patients with hepatic metastasis) Coagulation International normalized ratio (INR) or prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤1.5 × ULN, unless the subject is receiving anticoagulant therapy, in which case PT or aPTT must be within the therapeutic range of intended anticoagulation.
Who cannot join
- Female subjects of childbearing potential (WOCBP) with a positive urine pregnancy test within 72 hours prior to study enrollment (see Appendix 3). If the urine test is positive or inconclusive, a serum pregnancy test must be performed.
- Receipt of radiotherapy within 2 weeks prior to initiation of study intervention. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and have no evidence of radiation pneumonitis. For palliative radiotherapy to non-CNS disease (<2 weeks duration), a 1-week washout period is permitted.
- Receipt of a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Inactivated vaccines are allowed.
- Participation in another clinical study or receipt of systemic therapy (e.g., cytotoxic chemotherapy, immunotherapy, or investigational agents) within 4 weeks prior to the first dose of study intervention.
- Diagnosis of immunodeficiency, or receipt of chronic systemic steroid therapy (>10 mg/day prednisone equivalent) or other immunosuppressive therapy within 7 days prior to the first dose.
- In addition, subjects with a history of autoimmune disease requiring systemic treatment (e.g., disease-modifying agents, corticosteroids, immunosuppressants) within the past 2 years are excluded.
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- Exceptions include physiologic replacement therapy (e.g., thyroxine, insulin, or corticosteroid replacement for adrenal or pituitary insufficiency), which are permitted.
- Presence of another active malignancy or malignancy requiring treatment within the past 3 years.
- Exceptions include adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ (except carcinoma in situ of the bladder).
- Symptomatic CNS metastases or carcinomatous meningitis. Subjects with previously treated CNS metastases may participate if they are radiographically stable (no progression for ≥4 weeks on repeat imaging during screening), clinically stable, and do not require steroid treatment for at least 14 days prior to the first dose.
- Known severe hypersensitivity (≥ Grade 3) to pembrolizumab.
- History of (non-infectious) pneumonitis/interstitial lung disease requiring steroids, or current pneumonitis/interstitial lung disease.
- Active infection requiring systemic therapy.
- Active hepatitis B (HBsAg positive and/or detectable HBV DNA) or hepatitis C infection (anti-HCV positive with detectable HCV RNA).
- Any medical condition or evidence of disease that may confound study results or interfere with study participation, as judged by the investigator.
- Psychiatric or substance abuse disorders that would interfere with compliance with study requirements.
- Subjects who are pregnant, breastfeeding, or planning to become pregnant or father a child during the study period, from screening through 120 days after the last dose of study treatment.
- History of allogeneic tissue or solid organ transplantation.
- Concomitant use of strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) or strong CYP3A4 inhibitors (e.g., clarithromycin, grapefruit juice, itraconazole, ketoconazole, posaconazole, telithromycin, voriconazole).
- QTc interval >450 ms (male) or >470 ms (female), or history of congenital long QT syndrome or Torsades de pointes (TdP).
- Patients with UGT1A1 poor metabolizer genotype (e.g., *28/*28, *6/*6, *6/*28) or other clinically significant reduced-function UGT1A1 variants identified at screening (based on medical records or external test results) will be excluded in this study.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
This is a single-center, open-label, single-arm Phase 1b/2 clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of pembrolizumab in combination with irinotecan in patients with metastatic melanoma who have relapsed at least 6 months after completion of adjuvant pembrolizumab therapy or who are immune checkpoint inhibitor-naïve.
The study consists of two sequential parts: a Phase 1b safety lead-in and a Phase 2 efficacy evaluation using Simon's optimal two-stage design. During the Phase 1b portion, six patients will be enrolled to assess the initial safety and tolerability of the combination regimen. Dose-limiting toxicities (DLTs) will be evaluated during the first two treatment cycles (42 days). Following completion of the safety observation period, a safety review will be conducted. If fewer than two of six patients experience a DLT, the regimen will be considered adequately tolerable and the study will proceed to the Phase 2 portion. Patients enrolled in the Phase 1b portion will be included in the efficacy analysis of Phase 2.
Read more
In the Phase 2 portion, efficacy will be evaluated using Simon's optimal two-stage design with objective response rate (ORR) as the primary endpoint. The null hypothesis ORR is 30%, and the alternative hypothesis ORR is 50%, with a one-sided type I error rate of 5% and 80% power. In Stage 1, a total of 15 evaluable patients, including the six patients enrolled during the Phase 1b portion, will be assessed. If five or fewer objective responses are observed, the study will be terminated early for futility. If six or more responses are observed, additional patients will be enrolled in Stage 2. A total of 46 patients will be enrolled, and the regimen will be considered worthy of further investigation if at least 19 objective responses are observed.
Participants will receive pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle. Irinotecan 125 mg/m² will be administered intravenously on Days 1 and 8 beginning in Cycle 2. Cycle 1 consists of pembrolizumab monotherapy to allow evaluation of early immunologic changes induced by PD-1 blockade without potential interference from irinotecan. Blood and tumor samples will be collected at baseline and prior to irinotecan administration on Cycle 2 Day 1 for translational immune analyses.
Tumor assessments will be performed according to RECIST version 1.1 every 6 weeks during the first year and every 12 weeks thereafter. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), dose-limiting toxicity (DLT), and safety and tolerability as assessed by the incidence of adverse events graded according to CTCAE version 5.0. Exploratory analyses will evaluate tumor microenvironment characteristics and peripheral blood immune biomarkers, including immune cell phenotypes, cytokine profiles, and potential biomarkers associated with treatment response and resistance.
- Conditions
- Unresectable or Metastatic Melanoma
- Being tested
- Pembrolizumab and Irinotecan
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pembrolizumab and IrinotecanDrug
Participants will receive pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle. Cycle 1 consists of pembrolizumab monotherapy, and irinotecan 125 mg/m² will be added on Days 1 and 8 from Cycle 2 onward. The study includes a Phase 1b safety lead-in and a Phase 2 efficacy evaluation using Simon's optimal two-stage design. Treatment will continue for up to 35 cycles or until disease progression, unacceptable toxicity, or study discontinuation.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab Plus Irinotecan Combination Therapy | Experimental | Participants will receive pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle. Cycle 1 consists of pembrolizumab monotherapy to evaluate early immune changes induced by PD-1 blockade. Beginning in Cycle 2, irinotecan 125 mg/m² will be administered intravenously on Days 1 and 8 in combination with pembrolizumab. The study consists of a Phase 1b safety lead-in followed by a Phase 2 efficacy evaluation using Simon's optimal two-stage design. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, investigator decision, or completion of a maximum of 35 cycles. Receives: Drug: Pembrolizumab and Irinotecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Tumor response will be assessed according to RECIST version 1.1. ORR is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) as their best overall response.
Measured: up to 24 months.
Secondary outcomes (4)
Disease Control Rate (DCR)
Disease control rate is defined as the proportion of participants who achieve complete response (CR), partial response (PR), or stable disease (SD) as their best overall response according to RECIST version 1.1.
Measured: up to 5 years.
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from treatment initiation to the first documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
Measured: up to 5 years.
Overall Survival (OS)
Overall survival is defined as the time from treatment initiation until death from any cause.
Measured: Up to 5 years
Safety and Tolerability
Safety and tolerability will be assessed by the incidence, severity, and relationship to study treatment of adverse events (AEs), treatment-related adverse events (TRAAEs), and serious adverse events (SAEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Measured: up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2026
- Study start1 Nov 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion8 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable or Metastatic 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 46 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07817901
- Sponsor's protocol ID
- 4-2026-0382
- Status last verified
- Sep 2026
- First submitted
- 8 Sep 2026
- Last updated
- 14 Sep 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 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Combination Therapy With Pembrolizumab and Irinotecan in Patients With Metastatic or Recurrent Malignant Melanoma
- ClinicalTrials.gov ID
- NCT07817901
- Acronym / sponsor ID
- 4-2026-0382
- Conditions
- Unresectable or Metastatic Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 46 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 8 Jun 2028 (estimated)
- First posted
- 14 Sep 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 is a single-center, open-label, single-arm Phase 1b/2 clinical trial designed to evaluate the safety, tolerability, and preliminary efficacy of pembrolizumab in combination with irinotecan in patients with metastatic melanoma who have relapsed at least 6 months after completion of adjuvant pembrolizumab therapy or who are immune checkpoint inhibitor-naïve.
The study consists of two sequential parts: a Phase 1b safety lead-in and a Phase 2 efficacy evaluation using Simon's optimal two-stage design. During the Phase 1b portion, six patients will be enrolled to assess the initial safety and tolerability of the combination regimen. Dose-limiting toxicities (DLTs) will be evaluated during the first two treatment cycles (42 days). Following completion of the safety observation period, a safety review will be conducted. If fewer than two of six patients experience a DLT, the regimen will be considered adequately tolerable and the study will proceed to the Phase 2 portion. Patients enrolled in the Phase 1b portion will be included in the efficacy analysis of Phase 2.
In the Phase 2 portion, efficacy will be evaluated using Simon's optimal two-stage design with objective response rate (ORR) as the primary endpoint. The null hypothesis ORR is 30%, and the alternative hypothesis ORR is 50%, with a one-sided type I error rate of 5% and 80% power. In Stage 1, a total of 15 evaluable patients, including the six patients enrolled during the Phase 1b portion, will be assessed. If five or fewer objective responses are observed, the study will be terminated early for futility. If six or more responses are observed, additional patients will be enrolled in Stage 2. A total of 46 patients will be enrolled, and the regimen will be considered worthy of further investigation if at least 19 objective responses are observed.
Participants will receive pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle. Irinotecan 125 mg/m² will be administered intravenously on Days 1 and 8 beginning in Cycle 2. Cycle 1 consists of pembrolizumab monotherapy to allow evaluation of early immunologic changes induced by PD-1 blockade without potential interference from irinotecan. Blood and tumor samples will be collected at baseline and prior to irinotecan administration on Cycle 2 Day 1 for translational immune analyses.
Tumor assessments will be performed according to RECIST version 1.1 every 6 weeks during the first year and every 12 weeks thereafter. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease control rate (DCR), progression-free survival (PFS), overall survival (OS), dose-limiting toxicity (DLT), and safety and tolerability as assessed by the incidence of adverse events graded according to CTCAE version 5.0. Exploratory analyses will evaluate tumor microenvironment characteristics and peripheral blood immune biomarkers, including immune cell phenotypes, cytokine profiles, and potential biomarkers associated with treatment response and resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab Plus Irinotecan Combination Therapy | Experimental | Drug: Pembrolizumab and IrinotecanParticipants will receive pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle. Cycle 1 consists of pembrolizumab monotherapy to evaluate early immune changes induced by PD-1 blockade. Beginning in Cycle 2, irinotecan 125 mg/m² will be administered intravenously on Days 1 and 8 in combination with pembrolizumab. The study consists of a Phase 1b safety lead-in followed by a Phase 2 efficacy evaluation using Simon's optimal two-stage design. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, investigator decision, or completion of a maximum of 35 cycles. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients with histologically confirmed non-uveal melanoma, diagnosed as Stage IV or unresectable Stage III melanoma.
- Age ≥19 years at the time of signing the informed consent form.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
- Patients must be treatment-naïve in the metastatic or unresectable setting (first-line setting) and meet at least one of the following criteria:
- Patients with CNS metastases must have stable neurological function without evidence of CNS progression within 4 weeks prior to enrollment (i.e., treated/controlled or asymptomatic CNS metastases, or resected CNS metastases without radiographic evidence of disease).
Key exclusion criteria (21 listed)
- Female subjects of childbearing potential (WOCBP) with a positive urine pregnancy test within 72 hours prior to study enrollment (see Appendix 3). If the urine test is positive or inconclusive, a serum pregnancy test must be performed.
- Receipt of radiotherapy within 2 weeks prior to initiation of study intervention. Subjects must have recovered from all radiation-related toxicities, not require corticosteroids, and have no evidence of radiation pneumonitis. For palliative radiotherapy to non-CNS disease (<2 weeks duration), a 1-week washout period is permitted.
- Receipt of a live or live-attenuated vaccine within 30 days prior to the first dose of study drug. Inactivated vaccines are allowed.
- Participation in another clinical study or receipt of systemic therapy (e.g., cytotoxic chemotherapy, immunotherapy, or investigational agents) within 4 weeks prior to the first dose of study intervention.
- Diagnosis of immunodeficiency, or receipt of chronic systemic steroid therapy (>10 mg/day prednisone equivalent) or other immunosuppressive therapy within 7 days prior to the first dose.
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 and IrinotecanParticipants will receive pembrolizumab 200 mg intravenously on Day 1 of each 21-day cycle. Cycle 1 consists of pembrolizumab monotherapy, and irinotecan 125 mg/m² will be added on Days 1 and 8 from Cycle 2 onward. The study includes a Phase 1b safety lead-in and a Phase 2 efficacy evaluation using Simon's optimal two-stage design. Treatment will continue for up to 35 cycles or until disease progression, unacceptable toxicity, or study discontinuation. | Drug | Pembrolizumab Plus Irinotecan Combination Therapy |
Primary outcome
Overall Response Rate
Time frame: up to 24 months.
Tumor response will be assessed according to RECIST version 1.1. ORR is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) as their best overall response.
4 secondary outcomes
Disease Control Rate (DCR)
Time frame: up to 5 years.
Progression-Free Survival (PFS)
Time frame: up to 5 years.
Overall Survival (OS)
Time frame: Up to 5 years
Safety and Tolerability
Time frame: up to 24 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 14 Sep 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.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pembrolizumab and Irinotecan in people with Unresectable or Metastatic Melanoma, run by Yonsei University.
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 21 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: opening soon, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Sang Joon Shin, Professor (+82-2-2228-8138, ssj338@yuhs.ac), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (time frame: up to 24 months.). 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 14 Sep 2026.