Melanoma (Skin)Early Phase 1NCT02652455

Combining PD-1 Blockade, CD137 Agonism and Adoptive Cell Therapy for Metastatic Melanoma

A Early Phase 1 study testing Nivolumab, Surgery to Remove Tumor for Growth of TIL and CD137 in people with Melanoma (Skin) and Skin Cancer, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this Pilot Study is to investigate the safety, side effects, and benefits of tumor- infiltrating lymphocytes (TILs) when they are given with the drug nivolumab. Nivolumab is a type of immunotherapy - a drug that is used to boost the ability of the immune system to fight cancer, infection, and other… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Melanoma (Skin), Skin Cancer
What is being tested?: Nivolumab, Surgery to Remove Tumor for Growth of TIL and CD137
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 11 participants
Where: 1 siteUnited States
Study dates: 8 Mar 2016to 30 Aug 2020
Phase: Early Phase 1
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 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Must have unresectable cutaneous or mucosal metastatic stage III/IV melanoma, and in the opinion of the institutional principal investigator (PI) is an acceptable candidate for adoptive cell therapy (ACT) with high dose IL-2.
Must have anticipated residual measurable disease after resection of target lesion(s) for TIL growth.
Patients who have been previously treated for metastatic melanoma may be included (e.g., prior treatment with Rapidly Accelerated Fibrosarcoma (BRAF) inhibitors and/or ipilimumab will be allowed), provided that they have had a three week 'washout' prior to signing consent and have not been treated with a Programmed Death-1 (PD-1) blocking antibody.
Age greater than or equal to 18 years.
Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 - 1.
Women of childbearing potential must have a negative serum pregnancy test within seven days of screening and within 24 hours prior to the start of each nivolumab dose.

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Adequate renal, hepatic and hematologic function.
Patients must have a positive screening Epstein Barr Virus (EBV) antibody titer on screening test as this is required to protect against EBV infection during the time of lymphodepletion.
Patients with antibiotic allergies per se are not excluded; although the production of TIL for adoptive transfer includes antibiotics, extensive washing after harvest will minimize systemic exposure to antibiotics.
At screening, patients with ≤ 3 untreated central nervous system (CNS) metastases may be included provided none of the untreated lesions are > 1 cm in greatest dimension, and there is no peri-tumoral edema present on brain imaging (MRI or CT if MRI is contraindicated), and if the patients with CNS metastases are not taking prednisone >10 mg or equivalent daily.
At screening, patients with ≤ 3 CNS metastases and each ≤ 1 cm size that were treated with either surgical resection and/or radiation therapy may be included. Patients may be included if the largest lesion is ≤ 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 30 days after definitive treatment, and if the patients with CNS metastases are not taking prednisone >10 mg or equivalent daily.
At screening, patients with> 1 cm or > 3 in number treated CNS metastases may be included if there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy, and if the patients with CNS metastases are not taking prednisone >10 mg or equivalent daily.

Who cannot join

Patients with active systemic infections requiring intravenous antibiotics, coagulation disorders, or other major medical illness of the cardiovascular, respiratory or immune system, which in the opinion of the PI or treating co-investigator is not acceptable risk for ACT, are excluded.
Patients who have received prior immunotherapy whose side effects have resulted in a requirement of immunosuppressive medications (>10 mg of prednisone daily or equivalent daily steroid daily, or infliximab, cyclosporine or equivalent immunosuppressive medication) or who have other autoimmune conditions that require immunosuppressive medications as above at the time of screening are excluded.
Patients who test positive for Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen, Hepatitis B core antibody, Hepatitis C antibody, Human T-lymphotropic Virus (HTLV) I or II antibody, or are both Rapid plasma reagin (RPR) and Fluorescent treponemal antibody (FTA) positive are excluded.
Patients who are pregnant or nursing are excluded.
Patients with a significant psychiatric disease, who in the opinion of the principal investigator or his designee, would prevent adequate informed consent or render immunotherapy unsafe will be excluded.
Patients with > 3 untreated CNS metastases or evidence of peri-tumoral edema will be excluded, or patients with CNS metastases of any status who are taking prednisone >10 mg or equivalent steroid daily will be excluded.

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Patients with ≤ 3 untreated CNS metastases but with at least one lesion >1 cm or peri-tumoral edema will be excluded, or patients with CNS metastases of any status who are taking prednisone >10 mg or equivalent steroid daily will be excluded.
Patients with invasive malignancy other than melanoma at the time of enrollment and within 2 years of screening are excluded, except for: adequately treated (i.e. with curative intent) basal or squamous cell carcinoma, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer or other any other cancers from which the patient has been disease-free for at least 2 years.
Patients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy, or patients with CNS metastases of any status who are taking prednisone >10 mg or equivalent will be excluded.
Male patients with female partners of childbearing potential who do not agree to use two FDA-accepted forms of contraception during sexual intercourse with women of child-bearing potential from the start of PD-1 antibody therapy and up to at least 31 weeks from the last dose of nivolumab are excluded.
Females of childbearing potential who do not agree to use 2 FDA forms of contraception according to study guidelines
Prior systemic therapy with a PD-1 blocking antibody
Patients who are greater than age 50, or who have a history of coronary artery disease, will be required to undergo cardiac stress testing within 6 months of screening and will be excluded if there is evidence of reversible ischemia.
Patients who have a significant history of pulmonary disease that necessitates the use of supplemental oxygen, is associated with dyspnea on walking one block or less, or requires inhaler therapy more than once per week will be required to undergo pulmonary function testing within 6 months of screening and will be excluded if forced expiratory volume 1 (FEV1), forced vital capacity (FVC), or diffusion lung capacity for carbon monoxide (DLCO) is less than 65% of predicted.

Trial locations and contacts

1 site in 1 country.

United States1 site

H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Pilot Clinical Trial Combining PD-1 Blockade, CD137 Agonism and Adoptive Cell Therapy for Metastatic Melanoma

The primary endpoints of this pilot trial will be the safety and feasibility of the treatment regimens.

Conditions: Melanoma (Skin), Skin Cancer
Being tested: Nivolumab, Surgery to Remove Tumor for Growth of TIL, CD137, Cyclophosphamide, Fludarabine
Keywords: cutaneous, unresectable, mucosal metastatic stage III/IV melanoma
Medical subject headings: Melanoma, Skin Neoplasms

What participants receive

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

NivolumabDrug
Also called Opdivo, PD-1 blocking antibody, BMS-936558
Participants entering the study after the first 6 participants only: Treatment with nivolumab prior to removal of tumor sample for TIL growth. About 2 weeks after their tumor sample has been taken, these participants may receive additional infusions of nivolumab.
Surgery to Remove Tumor for Growth of TILProcedure or surgery
Also called Tumor Infiltrating Lymphocytes (TILs), T-cell
All participants: Tumor sample taken for growth of TILs. Growing the TILs takes about 4-8 weeks.
CD137Drug
Also called anti-CD137 agonistic antibody, BMS-663513, 4-1BB
All participants: Anti-CD137 agonistic antibody as an agent to augment T cell proliferation in vitro. The growth of the TIL will be accelerated by the use of CD137 activating antibody in the laboratory.
CyclophosphamideDrug
Also called Cytoxan
All participants: Lymphodepleting chemotherapy intravenously, beginning 3 to 6 weeks after tumor collection for TIL growth.
FludarabineDrug
Also called Fludara
All participants: Lymphodepleting chemotherapy intravenously, beginning after first 2 days of cyclophosphamide.
TIL InfusionBiological
After completing one week of lymphodepleting chemotherapy, all participants will be admitted back into the hospital for IV infusion of the TIL cells.
Interleukin-2Drug
Also called IL-2, Proleukin, Aldesleukin
After TIL infusion, in-patient high dose IL-2 treatment.

Study groups in NCT02652455
Study group	Role	What they receive
PD-1, CD137 and Adoptive Cell Therapy	Experimental	Combination Therapy and Immunotherapy as described in intervention descriptions. 1. Nivolumab Treatment: The first 6 participants will not have pre-treatment with nivolumab and instead will be scheduled for the removal of their tumor sample for tumor Infiltrating lymphocytes (TIL) growth in the lab. The second 6 participants will receive treatment with nivolumab prior to removal of tumor sample for TIL growth; about 2 weeks after their tumor sample has been taken, these participants may receive additional infusions of nivolumab. 2. Surgery to remove tumor for growth of TIL followed by: TIL growth process; lymphodepleting chemotherapy with cyclophosphamide and fludarabine; TIL infusion; Interleukin-2 treatment. Receives: Drug: Nivolumab; Procedure: Surgery to Remove Tumor for Growth of TIL; Drug: CD137; Drug: Cyclophosphamide; Drug: Fludarabine; Biological: TIL Infusion; Drug: Interleukin-2

What is being measured

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

Occurrence of Study Related Adverse Events
Safety will be determined by assessing toxicity based upon Common Terminology Criteria for Adverse Events (CTCAE) v4.
Measured: Up to 27 months

Timeline

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

8 Mar 201630 Aug 2020

First posted11 Jan 2016 (estimated)
Study start8 Mar 2016
Primary completion30 Aug 2020
Study completion30 Aug 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Melanoma (Skin)Studies 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: Early Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 11 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02652455
Sponsor's protocol ID: MCC-18377
Status last verified: Aug 2025
First submitted: 8 Jan 2016
Last updated: 19 Aug 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: 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

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Study at a glance

From the registry record, last updated by the sponsor on 19 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Pilot Clinical Trial Combining PD-1 Blockade, CD137 Agonism and Adoptive Cell Therapy for Metastatic Melanoma
ClinicalTrials.gov ID: NCT02652455
Acronym / sponsor ID: MCC-18377
Conditions: Melanoma (Skin), Skin Cancer
Keywords: cutaneous, unresectable, mucosal metastatic stage III/IV melanoma
Phase: Early Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 11 participants (actual)
Lead sponsor: H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
Collaborators: Bristol-Myers Squibb, Prometheus Inc., Iovance Biotherapeutics, Inc.
Study start: 8 Mar 2016 (actual)
Primary completion: 30 Aug 2020 (actual)
Study completion: 30 Aug 2020 (actual)
First posted: 11 Jan 2016 (estimated)
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 primary endpoints of this pilot trial will be the safety and feasibility of the treatment regimens.

Study design

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

Arm	Type	Receives
PD-1, CD137 and Adoptive Cell Therapy	Experimental	Drug: Nivolumab, Procedure: Surgery to Remove Tumor for Growth of TIL, Drug: CD137, Drug: Cyclophosphamide, Drug: Fludarabine, Biological: TIL Infusion, Drug: Interleukin-2Combination Therapy and Immunotherapy as described in intervention descriptions. 1. Nivolumab Treatment: The first 6 participants will not have pre-treatment with nivolumab and instead will be scheduled for the removal of their tumor sample for tumor Infiltrating lymphocytes (TIL) growth in the lab. The second 6 participants will receive treatment with nivolumab prior to removal of tumor sample for TIL growth; about 2 weeks after their tumor sample has been taken, these participants may receive additional infusions of nivolumab. 2. Surgery to remove tumor for growth of TIL followed by: TIL growth process; lymphodepleting chemotherapy with cyclophosphamide and fludarabine; TIL infusion; Interleukin-2 treatment.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Must have unresectable cutaneous or mucosal metastatic stage III/IV melanoma, and in the opinion of the institutional principal investigator (PI) is an acceptable candidate for adoptive cell therapy (ACT) with high dose IL-2.
Must have anticipated residual measurable disease after resection of target lesion(s) for TIL growth.
Patients who have been previously treated for metastatic melanoma may be included (e.g., prior treatment with Rapidly Accelerated Fibrosarcoma (BRAF) inhibitors and/or ipilimumab will be allowed), provided that they have had a three week 'washout' prior to signing consent and have not been treated with a Programmed Death-1 (PD-1) blocking antibody.
Age greater than or equal to 18 years.
Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 - 1.

Key exclusion criteria (14 listed)

Patients with active systemic infections requiring intravenous antibiotics, coagulation disorders, or other major medical illness of the cardiovascular, respiratory or immune system, which in the opinion of the PI or treating co-investigator is not acceptable risk for ACT, are excluded.
Patients who have received prior immunotherapy whose side effects have resulted in a requirement of immunosuppressive medications (>10 mg of prednisone daily or equivalent daily steroid daily, or infliximab, cyclosporine or equivalent immunosuppressive medication) or who have other autoimmune conditions that require immunosuppressive medications as above at the time of screening are excluded.
Patients who test positive for Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen, Hepatitis B core antibody, Hepatitis C antibody, Human T-lymphotropic Virus (HTLV) I or II antibody, or are both Rapid plasma reagin (RPR) and Fluorescent treponemal antibody (FTA) positive are excluded.
Patients who are pregnant or nursing are excluded.
Patients with a significant psychiatric disease, who in the opinion of the principal investigator or his designee, would prevent adequate informed consent or render immunotherapy unsafe will be excluded.

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
NivolumabAlso: Opdivo, PD-1 blocking antibody, BMS-936558Participants entering the study after the first 6 participants only: Treatment with nivolumab prior to removal of tumor sample for TIL growth. About 2 weeks after their tumor sample has been taken, these participants may receive additional infusions of nivolumab.	Drug	PD-1, CD137 and Adoptive Cell Therapy
Surgery to Remove Tumor for Growth of TILAlso: Tumor Infiltrating Lymphocytes (TILs), T-cellAll participants: Tumor sample taken for growth of TILs. Growing the TILs takes about 4-8 weeks.	Procedure or surgery	PD-1, CD137 and Adoptive Cell Therapy
CD137Also: anti-CD137 agonistic antibody, BMS-663513, 4-1BBAll participants: Anti-CD137 agonistic antibody as an agent to augment T cell proliferation in vitro. The growth of the TIL will be accelerated by the use of CD137 activating antibody in the laboratory.	Drug	PD-1, CD137 and Adoptive Cell Therapy
CyclophosphamideAlso: CytoxanAll participants: Lymphodepleting chemotherapy intravenously, beginning 3 to 6 weeks after tumor collection for TIL growth.	Drug	PD-1, CD137 and Adoptive Cell Therapy
FludarabineAlso: FludaraAll participants: Lymphodepleting chemotherapy intravenously, beginning after first 2 days of cyclophosphamide.	Drug	PD-1, CD137 and Adoptive Cell Therapy
TIL InfusionAfter completing one week of lymphodepleting chemotherapy, all participants will be admitted back into the hospital for IV infusion of the TIL cells.	Biological	PD-1, CD137 and Adoptive Cell Therapy
Interleukin-2Also: IL-2, Proleukin, AldesleukinAfter TIL infusion, in-patient high dose IL-2 treatment.	Drug	PD-1, CD137 and Adoptive Cell Therapy

Primary outcome

Occurrence of Study Related Adverse Events
Time frame: Up to 27 months
Safety will be determined by assessing toxicity based upon Common Terminology Criteria for Adverse Events (CTCAE) v4.

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2025.

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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.

Amod Sarnaik, M.D. principal investigator

H. Lee Moffitt Cancer Center and Research Institute

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 12 inclusion and 14 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: finished, as of the sponsor's last update on 19 Aug 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 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Occurrence of Study Related Adverse Events (time frame: Up to 27 months). 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 NCT02652455.

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 19 Aug 2025; AzTrials last refreshed its copy on 1 Nov 2026.