MelanomaPhase 2NCT03757689
Neoadjuvant PD-1 Blockade in Patients With Stage IIB/C Melanoma
A Phase 2 study testing Pembrolizumab and Wide Excision and Sentinel Lymph Node (SLN) Biopsy in people with Melanoma, run by Abramson Cancer Center at Penn Medicine at 3 sites in United States.
Trial summary
The main purpose of this study is to determine the rate of positive sentinel lymph nodes (i.e. the closest draining lymph node(s) to the primary melanoma site) and to test whether treatment with pembrolizumab before surgery to remove melanoma reduces the rate of positive sentinel lymph nodes in patients with Stage… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Pembrolizumab and Wide Excision and Sentinel Lymph Node (SLN) Biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- 3 sitesUnited States
- Study dates
- 6 May 2019to 1 Feb 2027
- 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
- The subject must have clinical stage IIB or IIC resectable MEL. Subjects may not have a diagnosis of uveal or mucosal melanoma.
- Either the subject or the subject's legal representative must be willing and able to provide written informed consent for the trial.
- The subject must be ≥18 years of age on day of signing informed consent.
- The subject must have a performance status of 0 or 1 on the ECOG Performance Scale.
- The subject must demonstrate adequate organ function as defined in Table 1; all screening labs must be performed within 21 days of treatment initiation.
- System Laboratory Value
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- Hematologic
- ANC ≥1500/mcL
- Platelets ≥100,000/mcL
- Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
- Renal
- Serum creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR
- ≥50 mL/min for subject with creatinine levels >1.5 X institutional ULN
- Hepatic
- Serum total bilirubin ≤1.5 X ULN OR
- Direct bilirubin ≤ ULN for subjects with total bilirubin levels >1.5 ULN
- AST (SGOT) and ALT (SPGT) ≤2.5 X ULN OR ≤5 X ULN for subjects with liver metastases
- Coagulation
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Female participants:
- 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:
- Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
- A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and must be willing to use 2 methods of contraception or abstain from heterosexual intercourse for at least 2 weeks prior to the time of first dose of study medication through 120 days after the last dose of study medication.
- Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication.
- Female subjects of childbearing potential are defined as those women who have not been surgically sterilized or have not been free from menses for >1 year.
- Male participants:
- Male subjects must agree to follow the contraceptive guidance in Appendix 3 starting with the first dose of study medication, while on study, through 120 days after the last dose of study medication.
Who cannot join
- Subject has unresectable disease; i.e. in the opinion of the surgical oncologist, all of the subject's melanoma cannot be completely removed with a clear margin.
- A woman of child bearing potential who has a positive urine pregnancy test within 72 hours prior to first dose of study drug (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), interferon, high dose IL-2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy are an exception to this criterion.
- If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
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- Subject has received transfusion of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to study Day 1.
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not 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 treatment.
- 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 requires active treatment. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
- 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 3 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has evidence of active interstitial lung disease or a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of Human Immunodeficiency Virus (HIV). (HIV 1/2 antibodies) as determined by medical record review.
- Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection as determined by medical record review.
- Has a known history of active TB (Bacillus Tuberculosis).
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject 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 severe cardiovascular disease, i.e. arrhythmias, requiring chronic treatment, congestive heart failure (NYHA Class III or IV) or symptomatic ischemic heart disease.
- Has hepatic decompensation (Child-Pugh score >6 [class B and C]).
- Has uncontrolled thyroid dysfunction.
- Has uncontrolled diabetes mellitus.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
University of Louisville
Louisville, Kentucky, 40202
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
The main purpose of this study is to determine the rate of positive sentinel lymph nodes (i.e. the closest draining lymph node(s) to the primary melanoma site) and to test whether treatment with pembrolizumab before surgery to remove melanoma reduces the rate of positive sentinel lymph nodes in patients with Stage IIB/C melanoma.
Subjects with stage II melanoma will receive one dose of pembrolizumab 200 mg, then undergo standard definitive surgery with wide excision and sentinel lymph node (SLN) biopsy approximately 3 weeks after the initial dose of pembrolizumab. Post-operatively, subjects will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks.
- Conditions
- Melanoma
- Being tested
- Pembrolizumab, Wide Excision and Sentinel Lymph Node (SLN) Biopsy
- Keywords
- Stage IIB/C
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Pre-Surgery: Pembrolizumab, one 200mg dose; Post-Surgery: Pembrolizumab, 200 mg every 3 weeks.
Wide Excision and Sentinel Lymph Node (SLN) BiopsyProcedure or surgery
Wide excision and SLN biopsy and pathologic assessment of tissue will be performed per standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant Pembrolizumab | Experimental | Subjects will receive one dose of pembrolizumab 200 mg. Approximately 3 weeks after the initial dose of pembrolizumab, subjects will undergo wide excision and sentinel lymph node (SLN) biopsy. Post-operatively, subjects will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks. Receives: Drug: Pembrolizumab; Procedure: Wide Excision and Sentinel Lymph Node (SLN) Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
SLN Positivity Rate
To determine the SLN positivity rate and test whether the SLN positivity rate is reduced in high risk stage II patients undergoing neoadjuvant PD-1 blockade.
Measured: 3 Weeks
Safety and Tolerability as measured by observed adverse events.
All observed adverse events which occur anytime from the initiation of study therapy to 30 days after the final dose of pembrolizumab will be graded and tabled.
Measured: Approximately 5 Years
Secondary outcomes (2)
Disease-Free Survival (DFS)
Disease-free survival (DFS) is defined as the time from date of surgery to date of first documented disease progression, death due to any cause or last date that patient was documented to be disease-free (i.e., a scan date).
Measured: Approximately 5 Years
Overall Survival
Overall survival (OS) is defined as the time from date of surgery to date of death due to any cause or last patient contact alive. Both DFS and OS outcomes will be measured from date of surgery to allow us to compare DFS and OS estimates with those of other adjuvant trials.
Measured: Approximately 5 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2018
- Study start6 May 2019
- Primary completion13 Nov 2025
- Study completion1 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- 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
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Giorgos Karakousis, MD, Principal investigator, Abramson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03757689
- Sponsor's protocol ID
- UPCC 09618
- Other IDs
- 832023, CRU
- Status last verified
- Oct 2026
- First submitted
- 26 Nov 2018
- Last updated
- 9 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant PD-1 Blockade in Patients With Stage IIB/C Melanoma
- ClinicalTrials.gov ID
- NCT03757689
- Acronym / sponsor ID
- UPCC 09618
- Conditions
- Melanoma
- Keywords
- Stage IIB/C
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- 6 May 2019 (actual)
- Primary completion
- 13 Nov 2025 (actual)
- Study completion
- 1 Feb 2027 (estimated)
- First posted
- 29 Nov 2018 (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.
The main purpose of this study is to determine the rate of positive sentinel lymph nodes (i.e. the closest draining lymph node(s) to the primary melanoma site) and to test whether treatment with pembrolizumab before surgery to remove melanoma reduces the rate of positive sentinel lymph nodes in patients with Stage IIB/C melanoma.
Subjects with stage II melanoma will receive one dose of pembrolizumab 200 mg, then undergo standard definitive surgery with wide excision and sentinel lymph node (SLN) biopsy approximately 3 weeks after the initial dose of pembrolizumab. Post-operatively, subjects will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant Pembrolizumab | Experimental | Drug: Pembrolizumab, Procedure: Wide Excision and Sentinel Lymph Node (SLN) BiopsySubjects will receive one dose of pembrolizumab 200 mg. Approximately 3 weeks after the initial dose of pembrolizumab, subjects will undergo wide excision and sentinel lymph node (SLN) biopsy. Post-operatively, subjects will receive up to 1 year of adjuvant pembrolizumab 200 mg every 3 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (28 listed)
- The subject must have clinical stage IIB or IIC resectable MEL. Subjects may not have a diagnosis of uveal or mucosal melanoma.
- Either the subject or the subject's legal representative must be willing and able to provide written informed consent for the trial.
- The subject must be ≥18 years of age on day of signing informed consent.
- The subject must have a performance status of 0 or 1 on the ECOG Performance Scale.
- The subject must demonstrate adequate organ function as defined in Table 1; all screening labs must be performed within 21 days of treatment initiation.
Key exclusion criteria (25 listed)
- Subject has unresectable disease; i.e. in the opinion of the surgical oncologist, all of the subject's melanoma cannot be completely removed with a clear margin.
- A woman of child bearing potential who has a positive urine pregnancy test within 72 hours prior to first dose of study drug (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
- Note: In the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137), interferon, high dose IL-2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy are an exception to this criterion.
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 |
|---|---|---|
| PembrolizumabPre-Surgery: Pembrolizumab, one 200mg dose; Post-Surgery: Pembrolizumab, 200 mg every 3 weeks. | Drug | Neoadjuvant Pembrolizumab |
| Wide Excision and Sentinel Lymph Node (SLN) BiopsyWide excision and SLN biopsy and pathologic assessment of tissue will be performed per standard of care. | Procedure or surgery | Neoadjuvant Pembrolizumab |
Primary outcome
SLN Positivity Rate
Time frame: 3 Weeks
To determine the SLN positivity rate and test whether the SLN positivity rate is reduced in high risk stage II patients undergoing neoadjuvant PD-1 blockade.
Safety and Tolerability as measured by observed adverse events.
Time frame: Approximately 5 Years
All observed adverse events which occur anytime from the initiation of study therapy to 30 days after the final dose of pembrolizumab will be graded and tabled.
2 secondary outcomes
Disease-Free Survival (DFS)
Time frame: Approximately 5 Years
Overall Survival
Time frame: Approximately 5 Years
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 9 Oct 2026.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
Giorgos Karakousis, MD principal investigator
Abramson Cancer Center
3 sites 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 and Wide Excision and Sentinel Lymph Node (SLN) Biopsy in people with Melanoma, run by Abramson Cancer Center at Penn Medicine at 3 sites in United States.
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 28 inclusion and 25 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: under way, not looking for participants, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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?
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?
SLN Positivity Rate (time frame: 3 Weeks). 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 9 Oct 2026; AzTrials last refreshed its copy on 31 Oct 2026.