MelanomaPhase 2NCT03991130
High Dose IL-2 in Combination With Anti-PD-1
A Phase 2 study testing IL-2 and Nivolumab in people with Melanoma and Renal Cell Carcinoma, Metastatic, run by Gregory Daniels at 1 site in United States.
Trial summary
The primary objective of this single arm phase 2 trial is to assess the response rate [complete response (CR) + partial response (PR)] of combined nivolumab and HD IL-2 in subjects with metastatic melanoma and renal cell carcinoma. Response will be performed after each course of nivolumab and IL-2 using RECIST 1.1. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma, Renal Cell Carcinoma, Metastatic
- What is being tested?
- IL-2 and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jul 2019to 16 Aug 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patient has the ability to understand and the willingness to sign a written informed consent.
- Age ≥ 18 years at the time of consent.
- At least 6 weeks of prior anti-PD-1 therapy with documented clinical or radiographic progression. Last anti-PD-1 therapy must be within 6 months of enrollment.
- Histologically-confirmed diagnosis of unresectable stage III or metastatic (stage IV) melanoma or renal cell carcinoma
- Measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1, and obtained by imaging within 28 days prior registration for protocol therapy.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 days prior to registration for protocol therapy.
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- Adequate hepatic function within 28 days prior to registration for protocol therapy defined as meeting all of the following criteria:
- total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 x ULN (except in patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl.)
- and aspartate aminotransferase (AST) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
- and alanine aminotransferase (ALT) ≤ 2.5 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
- Adequate renal function within 28 days prior to registration for protocol therapy defined by either of the following criteria:
- Serum creatinine ≤ 1.5 mg/dL
- OR if serum creatinine > 1.5 mg/dL, estimated glomerular filtration rate (GFR) ≥ 50 mL/min
- Adequate hematologic function within 28 days prior to registration for protocol therapy defined as meeting all of the following criteria:
- hemoglobin ≥ 9.0 g/dL
- and absolute neutrophil count (ANC) ≥ 1000/L without the support of filgrastim
- white blood cells (WBC) ≥ 3000/L
- and platelet count ≥ 100 × 109/L
- Adequate coagulation functioning within 28 days prior to registration for protocol therapy defined by either of the following criteria:
- INR < 1.5 × ULN
- OR for subjects receiving warfarin or LMWH, the subjects must, in the investigator's opinion, be clinically stable with no evidence of active bleeding while receiving anticoagulant therapy. The INR for these subjects may exceed 1.5 × ULN if that is the goal of anticoagulant therapy.
- Adequate pulmonary and cardiac function for HD IL-2 (will be assessed clinically)
- Female subjects of childbearing potential must have confirmed negative urine or serum pregnancy test prior to drug administration and be willing to use two methods of birth control.
- Male subjects who are not surgically sterile (vasectomy) must agree to use an adequate method of contraception.
- Subject's toxicities from prior treatments must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo)
Who cannot join
- Active infection requiring systemic therapy
- Women who are pregnant or breastfeeding.
- Second active malignancy within the past 5 years with the exception of localized basal or squamous cell skin cancer, in situ cervical or bladder cancer, or localized prostate cancer under active surveillance.
- Active symptomatic central nervous system (CNS) metastases. Prior treated metastases or asymptomatic metastases are allowed. Patient can receive radiation between treatments if deemed medically necessary.
- Surgery within 4 weeks prior to study treatment except for minor procedures.
- Uncontrolled or poorly-controlled hypertension (> 160 mmHg systolic or > 100 mmHg diastolic for > 4 weeks) despite standard medical management.
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- Serious or non-healing wounds, ulcers, or bone fractures within 28 days prior to initiation of study treatment.
- Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to initiation of study treatment.
- Has any condition that, in the opinion of the investigator, might jeopardize the safety of the patient or interfere with protocol compliance.
- Has any mental or medical condition that prevents the patient from giving informed consent or participating in the trial.
- Known hypersensitivity to nivolumab or IL-2 or any of their components.
- Known history of active tuberculosis.
- Concurrent systemic steroid therapy with doses above physiologic level (more than 10 mg of prednisone daily).
- Active autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis requiring treatment. Patients cannot be on immunosuppressive medications other than physiologic replacement doses of prednisone (less than 10 mg per day at enrollment) or equivalent steroid. Asymptomatic patients or those stable on non-immunosuppressive medications are eligible.
- Treatment with any investigational agent within 21 days prior to initiation of study treatment and the subject must have recovered from the acute toxic effects of the regimen with the exception of prior anti-PD-1.
Trial locations and contacts
1 site in 1 country.
United States1 site
UC San Diego Moores Cancer Center
La Jolla, California, 92093
About this study
Official title: High Dose IL-2 in Combination With Anti-PD-1 to Overcome Anti-PD-1 Resistance in Metastatic Melanoma and Renal Cell Carcinoma
The primary objective of this single arm phase 2 trial is to assess the response rate [complete response (CR) + partial response (PR)] of combined nivolumab and HD IL-2 in subjects with metastatic melanoma and renal cell carcinoma. Response will be performed after each course of nivolumab and IL-2 using RECIST 1.1. Patients will be treated for one course past best response for a maximum of 3 courses.
Read the detailed description
PrimaryObjective Determine the overall response rate (complete response and partial response) for patients receiving anti-PD-1 (nivolumab) and high dose IL-2 (HD IL-2) in subjects with metastatic melanoma or renal cell carcinoma who have previously progressed on anti-PD-1 therapy. Response assessment will be performed using revised RECIST guideline (v 1.1).
Secondary Objectives
- Characterize safety, tolerability and adverse effects (AE) profile of nivolumab with HD IL-2 in subjects with metastatic malignant melanoma or renal cell carcinoma
- Measure Progression-Free Survival (PFS) using RECIST 1.1 after completion of at least one course of therapy (2 doses of nivolumab, 2 cycles of HD IL-2) for subjects enrolled in the study.
ExploratoryObjectives
- Correlate PD-L1 expression and tumor mutational burden (TMB) in archived diagnostic tumor tissue with best clinical response for subjects with metastatic melanoma and renal cell carcinoma
- Correlate myeloid-derived suppressor cells and T-cell subsets in peripheral blood during therapy with best clinical response (RECIST criteria) and treatment outcome in subjects with metastatic melanoma or renal cell carcinoma. Data will be collected prior to each treatment and after each course of treatment.
Study Duration: 48 months Amount of Subjects: up to 25 subjects
- Conditions
- Melanoma, Renal Cell Carcinoma, Metastatic
- Being tested
- IL-2 and Nivolumab
- Keywords
- melanoma, renal cell carcinoma
- Medical subject headings
- Melanoma, Carcinoma, Renal Cell, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IL-2 and NivolumabDrug
Also called High Dose IL-2, Anti-PD-1
Course length will be 35 days. Subjects will receive 480 mg IV of nivolumab on day 1 of the cycle. The patient will be admitted to UCSD Jacobs Medical center for standard HD IL-2 which will be administered every 8 hrs for up to 14 doses days 8-12 per institutional practice. The patient will be readmitted days 22-28 for HD IL-2 every 8 hrs for up to 14 doses. Nivolumab 480 mg IV will be administered day 35. Scans for response will occur 4 weeks after day 35 nivolumab dose and response will be determined by RECIST 1.1 to determine if the patient will receive the next course.
| Study group | Role | What they receive |
|---|---|---|
| High Dose IL-2 and Nivolumab | Experimental | Not described Receives: Drug: IL-2 and Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate
Overall response rate of combined therapy with nivolumab and HD IL-2 in metastatic melanoma and renal cell carcinoma evaluated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.1) for target lesions: complete response (CR), disappearance of all target lesions; partial response (PR), ≥ 30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR + PR
Measured: Up to 45 months
Secondary outcomes (2)
Drug Toxicity
Percentage of subjects with grade 3 or higher adverse events as defined by CTCAE v 5.0
Measured: Up to 6 months or start of a new anti-cancer therapy or death
Progression Free Survival
Progression Free Survival of combined therapy with nivolumab and HD IL-2 in metastatic melanoma and renal cell carcinoma evaluated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.1): 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Up to 45 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2019
- Study start17 Jul 2019
- Primary completion7 Feb 2023
- Study completion16 Aug 2024
Why it stopped: Lack of funding
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gregory Daniels
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Gregory Daniels, University of California, San Diego
- Investigators
- Gregory Daniels, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03991130
- Sponsor's protocol ID
- UCSD IIT HD IL-2
- Status last verified
- Jul 2026
- First submitted
- 16 Jun 2019
- Last updated
- 6 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Azenkot T, Nikanjam M, Mhatre S, Mullen JT, Barkauskas DA, McKay RR, Baumgartner JM, Daniels GA. High dose interleukin-2 in combination with anti-programmed cell death protein 1 to overcome immune checkpoint inhibitor resistance in metastatic melanoma and renal cell carcinoma. Melanoma Res. 2026 Apr 30. doi: 10.1097/CMR.0000000000001102. Online ahead of print.
PubMed 42070986
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High Dose IL-2 in Combination With Anti-PD-1 to Overcome Anti-PD-1 Resistance in Metastatic Melanoma and Renal Cell Carcinoma
- ClinicalTrials.gov ID
- NCT03991130
- Acronym / sponsor ID
- UCSD IIT HD IL-2
- Conditions
- Melanoma, Renal Cell Carcinoma, Metastatic
- Keywords
- melanoma, renal cell carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of funding
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Gregory DanielsUniversity, hospital or other
- Study start
- 17 Jul 2019 (actual)
- Primary completion
- 7 Feb 2023 (actual)
- Study completion
- 16 Aug 2024 (actual)
- First posted
- 19 Jun 2019 (actual)
- Results
- Posted 6 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this single arm phase 2 trial is to assess the response rate [complete response (CR) + partial response (PR)] of combined nivolumab and HD IL-2 in subjects with metastatic melanoma and renal cell carcinoma. Response will be performed after each course of nivolumab and IL-2 using RECIST 1.1. Patients will be treated for one course past best response for a maximum of 3 courses.
Detailed description
PrimaryObjective Determine the overall response rate (complete response and partial response) for patients receiving anti-PD-1 (nivolumab) and high dose IL-2 (HD IL-2) in subjects with metastatic melanoma or renal cell carcinoma who have previously progressed on anti-PD-1 therapy. Response assessment will be performed using revised RECIST guideline (v 1.1).
Secondary Objectives
- Characterize safety, tolerability and adverse effects (AE) profile of nivolumab with HD IL-2 in subjects with metastatic malignant melanoma or renal cell carcinoma
- Measure Progression-Free Survival (PFS) using RECIST 1.1 after completion of at least one course of therapy (2 doses of nivolumab, 2 cycles of HD IL-2) for subjects enrolled in the study.
ExploratoryObjectives
- Correlate PD-L1 expression and tumor mutational burden (TMB) in archived diagnostic tumor tissue with best clinical response for subjects with metastatic melanoma and renal cell carcinoma
- Correlate myeloid-derived suppressor cells and T-cell subsets in peripheral blood during therapy with best clinical response (RECIST criteria) and treatment outcome in subjects with metastatic melanoma or renal cell carcinoma. Data will be collected prior to each treatment and after each course of treatment.
Study Duration: 48 months Amount of Subjects: up to 25 subjects
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| High Dose IL-2 and Nivolumab | Experimental | Drug: IL-2 and Nivolumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Patient has the ability to understand and the willingness to sign a written informed consent.
- Age ≥ 18 years at the time of consent.
- At least 6 weeks of prior anti-PD-1 therapy with documented clinical or radiographic progression. Last anti-PD-1 therapy must be within 6 months of enrollment.
- Histologically-confirmed diagnosis of unresectable stage III or metastatic (stage IV) melanoma or renal cell carcinoma
- Measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1, and obtained by imaging within 28 days prior registration for protocol therapy.
Key exclusion criteria (15 listed)
- Active infection requiring systemic therapy
- Women who are pregnant or breastfeeding.
- Second active malignancy within the past 5 years with the exception of localized basal or squamous cell skin cancer, in situ cervical or bladder cancer, or localized prostate cancer under active surveillance.
- Active symptomatic central nervous system (CNS) metastases. Prior treated metastases or asymptomatic metastases are allowed. Patient can receive radiation between treatments if deemed medically necessary.
- Surgery within 4 weeks prior to study treatment except for minor procedures.
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 |
|---|---|---|
| IL-2 and NivolumabAlso: High Dose IL-2, Anti-PD-1Course length will be 35 days. Subjects will receive 480 mg IV of nivolumab on day 1 of the cycle. The patient will be admitted to UCSD Jacobs Medical center for standard HD IL-2 which will be administered every 8 hrs for up to 14 doses days 8-12 per institutional practice. The patient will be readmitted days 22-28 for HD IL-2 every 8 hrs for up to 14 doses. Nivolumab 480 mg IV will be administered day 35. Scans for response will occur 4 weeks after day 35 nivolumab dose and response will be determined by RECIST 1.1 to determine if the patient will receive the next course. | Drug | High Dose IL-2 and Nivolumab |
Primary outcome
Overall Response Rate
Time frame: Up to 45 months
Overall response rate of combined therapy with nivolumab and HD IL-2 in metastatic melanoma and renal cell carcinoma evaluated per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.1) for target lesions: complete response (CR), disappearance of all target lesions; partial response (PR), ≥ 30% decrease in the sum of the longest diameter of target lesions; overall response (OR) = CR + PR
2 secondary outcomes
Drug Toxicity
Time frame: Up to 6 months or start of a new anti-cancer therapy or death
Progression Free Survival
Time frame: Up to 45 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42070986Azenkot T, Nikanjam M, Mhatre S, Mullen JT, Barkauskas DA, McKay RR, Baumgartner JM, Daniels GA. High dose interleukin-2 in combination with anti-programmed cell death protein 1 to overcome immune checkpoint inhibitor resistance in metastatic melanoma and renal cell carcinoma. Melanoma Res. 2026 Apr 30. doi: 10.1097/CMR.0000000000001102. Online ahead of print.
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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.
Gregory Daniels principal investigator
University of California, San Diego
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 IL-2 and Nivolumab in people with Melanoma and Renal Cell Carcinoma, Metastatic, run by Gregory Daniels at 1 site 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 25 inclusion and 15 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 6 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
Yes. Results are posted in the registry (first posted 6 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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: Up to 45 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 NCT03991130, which also lists 1 linked publication.
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 6 Aug 2026.