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MelanomaPhase 2NeoRelapseNCT06365619

Neoadjuvant Ipilimumab/Nivolumab for Patients With Recurrent, High Risk, Resectable Melanoma

A Phase 2 study testing Ipilimumab and Nivolumab in people with Melanoma, run by University of Utah.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The goal of this clinical trial is to study the impact of Neoadjuvant ipilimumab and nivolumab for melanoma patients that had recurrence during or after adjuvant anti-PD-1 therapy. Participants will receive 2 cycles of treatment prior to their standard of care surgery. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Ipilimumab and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Oct 2026to Oct 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects aged ≥ 18 years.
  • Histologically confirmed Stage IIIB-D or Stage IV recurrent metastatic melanoma that is resectable or borderline resectable as determined by a Surgical Oncologist.
  • Recurrent disease at eligibility must have been confirmed with biopsy after receiving prior anti-PD1 based systemic therapy (either adjuvant, neoadjuvant, or definitive therapy).
  • ECOG Performance Status ≤ 1.
  • Adequate organ function as defined as:
  • Hematologic:
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  • Absolute neutrophil count (ANC) ≥ 1500/mm3
  • Platelet count ≥ 100,000/mm3
  • Hemoglobin ≥ 10 g/dL
  • Hepatic:
  • Total Bilirubin ≤ 1.5x institutional upper limit of normal (ULN)
  • AST(SGOT)/ALT(SGPT) ≤ 3 × institutional ULN
  • Subjects with liver metastases will be allowed to enroll with AST and ALT levels ≤ 5 x ULN.
  • Renal:
  • Estimated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula:
  • For subjects of childbearing potential: Negative pregnancy test or evidence of post-menopausal status or evidence of permanent surgical sterilization. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
  • Subjects < 50 years of age:
  • Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
  • Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution
  • Subjects ≥ 50 years of age:
  • Amenorrheic for ≥ 12 months following cessation of all exogenous hormonal treatments; or
  • Had radiation-induced menopause with last menses >1 year ago; or
  • Had chemotherapy-induced menopause with last menses >1 year ago
  • Subjects of childbearing potential and subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception.
  • Recovery to baseline or ≤ Grade 1 CTCAE v5 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy per the treating investigator.
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Who cannot join

  • Prior exposure to anti-CTLA4 therapy.
  • Receiving other investigational agents currently or within 28 days of study treatment.
  • Prior systemic anti-cancer therapy ≤ 14 days or within five half-lives prior to starting study treatment, whichever is shorter.
  • Prior radiotherapy 45 days prior to the first dose of study treatment.
  • Major surgery 4 weeks prior to starting study drug or who have not fully recovered from major surgery.
  • Active infection requiring the use of systemic antibiotics.
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  • Systemic steroid therapy greater than physiologic equivalent (10mg prednisone/day) or any other form of systemic immunosuppressive therapy within 7 days prior to registration.
  • Active secondary malignancy, unless the malignancy is not expected to interfere with the evaluation of safety
  • Known brain metastases or cranial epidural disease.
  • Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Congestive heart failure New York Heart Association Class III or IV, unstable angina pectoris, serious cardiac arrhythmias.
  • Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic events, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 3 months before the first dose.
  • QTc prolongation defined as a QTcF > 500 ms.
  • Known congenital long QT.
  • Left ventricular ejection fraction < 55%.
  • Uncontrolled hypertension defined as ≥ 140/90 as assessed from the mean of three consecutive blood pressure measurements taken over 10 minutes.
  • Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, [subjects may not receive the drug through a feeding tube], social/psychological issues, etc.)
  • HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.
  • --Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
  • Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and TB testing in line with local practice), hepatitis B (positive HBV surface antigen (HBsAg) result), or hepatitis C.
  • --Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
  • Known prior severe hypersensitivity to investigational product (IP) or any component in its formulations (NCI CTCAE v5.0 Grade ≥ 3).
  • Subjects taking prohibited medications as described in Section 6.7.2. A washout period of prohibited medications for a period of at least five half-lives or as clinically indicated should occur before the start of treatment.

About this study

Official title: Phase II Study of Neoadjuvant Ipilimumab/Nivolumab for Patients With Recurrent, High Risk, Resectable Melanoma

The goal of this clinical trial is to study the impact of Neoadjuvant ipilimumab and nivolumab for melanoma patients that had recurrence during or after adjuvant anti-PD-1 therapy.

Participants will receive 2 cycles of treatment prior to their standard of care surgery. After surgery participants will receive standard of care adjuvant therapy and be followed for response.

Conditions
Melanoma
Being tested
Ipilimumab, Nivolumab
Medical subject headings
Melanoma

What participants receive

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

  • IpilimumabDrug

    Two cycles of neoadjuvant ipilimumab prior to surgical resection.

  • NivolumabDrug

    two cycles of neoadjuvant nivolumab prior to surgical resection.

Study groups in NCT06365619
Study groupRoleWhat they receive
Treatment: All PatientsExperimentalNeoadjuvant Ipilimumab and Nivolumab
Receives: Drug: Ipilimumab; Drug: Nivolumab

What is being measured

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

  1. Rate of pathologic response rate (pCR, mCR/nCR, or pPR) at the time of surgery.

    Assess the pathologic response rate (pRR) at the time of surgery after two doses of neoadjuvant Ipilimumab and Nivolumab for patients with resectable disease that have recurred after receiving systemic anti-PD1 therapy.

    Measured: 2 months

Secondary outcomes (5)

  1. Frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0), seriousness, duration, and relationship to study treatment.

    Assess the safety and tolerability of Ipilimumab and Nivolumab in the study population.

    Measured: 2 months

  2. Rate of adverse events that occur within 30 days post-surgery.

    Assess the impact of neoadjuvant ipi/nivo on morbidity of definitive surgery.

    Measured: 30 days

  3. Rate of Event Free Survival (EFS).

    Assess EFS in the study population.

    Measured: 11 years

  4. Rate of Overall Survival (OS).

    Assess OS in this study population.

    Measured: 11 years

  5. Objective response rate (ORR) defined as the proportion of subjects achieving a confirmed PR and CR as defined by RECIST 1.1 prior to surgical resection.

    Determine RECIST 1.1 response rate (confirmed CR and PR) before surgical resection and to evaluate associations between radiographic and pathologic response rate and event free survival/overall survival.

    Measured: 11 years

Timeline

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

  1. First posted15 Apr 2024
  2. Study startOct 2026 (estimated)
  3. Primary completionOct 2026 (estimated)
  4. Study completionOct 2026 (estimated)

Why it stopped: Low Accrual

Resources

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06365619
Sponsor's protocol ID
168525
Acronym
NeoRelapse
Status last verified
Jun 2026
First submitted
9 Apr 2024
Last updated
19 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Eggermont AMM, Blank CU, Mandala M, Long GV, Atkinson VG, Dalle S, Haydon AM, Meshcheryakov A, Khattak A, Carlino MS, Sandhu S, Larkin J, Puig S, Ascierto PA, Rutkowski P, Schadendorf D, Koornstra R, Hernandez-Aya L, Di Giacomo AM, van den Eertwegh AJM, Grob JJ, Gutzmer R, Jamal R, Lorigan PC, van Akkooi ACJ, Krepler C, Ibrahim N, Marreaud S, Kicinski M, Suciu S, Robert C; EORTC Melanoma Group. Adjuvant pembrolizumab versus placebo in resected stage III melanoma (EORTC 1325-MG/KEYNOTE-054): distant metastasis-free survival results from a double-blind, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):643-654. doi: 10.1016/S1470-2045(21)00065-6. Epub 2021 Apr 12.

    PubMed 33857412

  • Grossmann KF, Othus M, Patel SP, Tarhini AA, Sondak VK, Knopp MV, Petrella TM, Truong TG, Khushalani NI, Cohen JV, Buchbinder EI, Kendra K, Funchain P, Lewis KD, Conry RM, Chmielowski B, Kudchadkar RR, Johnson DB, Li H, Moon J, Eroglu Z, Gastman B, Kovacsovics-Bankowski M, Gunturu KS, Ebbinghaus SW, Ahsan S, Ibrahim N, Sharon E, Korde LA, Kirkwood JM, Ribas A. Adjuvant Pembrolizumab versus IFNalpha2b or Ipilimumab in Resected High-Risk Melanoma. Cancer Discov. 2022 Mar 1;12(3):644-653. doi: 10.1158/2159-8290.CD-21-1141.

    PubMed 34764195

  • Kirkwood JM, Del Vecchio M, Weber J, Hoeller C, Grob JJ, Mohr P, Loquai C, Dutriaux C, Chiarion-Sileni V, Mackiewicz J, Rutkowski P, Arenberger P, Quereux G, Meniawy TM, Ascierto PA, Menzies AM, Durani P, Lobo M, Campigotto F, Gastman B, Long GV. Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial. Nat Med. 2023 Nov;29(11):2835-2843. doi: 10.1038/s41591-023-02583-2. Epub 2023 Oct 16.

    PubMed 37845511

  • Long GV, Hauschild A, Santinami M, Atkinson V, Mandala M, Chiarion-Sileni V, Larkin J, Nyakas M, Dutriaux C, Haydon A, Robert C, Mortier L, Schachter J, Schadendorf D, Lesimple T, Plummer R, Ji R, Zhang P, Mookerjee B, Legos J, Kefford R, Dummer R, Kirkwood JM. Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med. 2017 Nov 9;377(19):1813-1823. doi: 10.1056/NEJMoa1708539. Epub 2017 Sep 10.

    PubMed 28891408

  • Luke JJ, Rutkowski P, Queirolo P, Del Vecchio M, Mackiewicz J, Chiarion-Sileni V, de la Cruz Merino L, Khattak MA, Schadendorf D, Long GV, Ascierto PA, Mandala M, De Galitiis F, Haydon A, Dummer R, Grob JJ, Robert C, Carlino MS, Mohr P, Poklepovic A, Sondak VK, Scolyer RA, Kirkwood JM, Chen K, Diede SJ, Ahsan S, Ibrahim N, Eggermont AMM; KEYNOTE-716 Investigators. Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma (KEYNOTE-716): a randomised, double-blind, phase 3 trial. Lancet. 2022 Apr 30;399(10336):1718-1729. doi: 10.1016/S0140-6736(22)00562-1. Epub 2022 Apr 1.

    PubMed 35367007

  • Weber J, Mandala M, Del Vecchio M, Gogas HJ, Arance AM, Cowey CL, Dalle S, Schenker M, Chiarion-Sileni V, Marquez-Rodas I, Grob JJ, Butler MO, Middleton MR, Maio M, Atkinson V, Queirolo P, Gonzalez R, Kudchadkar RR, Smylie M, Meyer N, Mortier L, Atkins MB, Long GV, Bhatia S, Lebbe C, Rutkowski P, Yokota K, Yamazaki N, Kim TM, de Pril V, Sabater J, Qureshi A, Larkin J, Ascierto PA; CheckMate 238 Collaborators. Adjuvant Nivolumab versus Ipilimumab in Resected Stage III or IV Melanoma. N Engl J Med. 2017 Nov 9;377(19):1824-1835. doi: 10.1056/NEJMoa1709030. Epub 2017 Sep 10.

    PubMed 28891423

  • Eroglu Z, Broman KK, Thompson JF, Nijhuis A, Hieken TJ, Kottschade L, Farma JM, Hotz M, Deneve J, Fleming M, Bartlett EK, Sharma A, Dossett L, Hughes T, Gyorki DE, Downs J, Karakousis G, Song Y, Lee A, Berman RS, van Akkooi A, Stahlie E, Han D, Vetto J, Beasley G, Farrow NE, Hui JYC, Moncrieff M, Nobes J, Baecher K, Perez M, Lowe M, Ollila DW, Collichio FA, Bagge RO, Mattsson J, Kroon HM, Chai H, Teras J, Sun J, Carr MJ, Tandon A, Babacan NA, Kim Y, Naqvi M, Zager J, Khushalani NI. Outcomes with adjuvant anti-PD-1 therapy in patients with sentinel lymph node-positive melanoma without completion lymph node dissection. J Immunother Cancer. 2022 Aug;10(8):e004417. doi: 10.1136/jitc-2021-004417.

    PubMed 36002183

  • Owen CN, Shoushtari AN, Chauhan D, Palmieri DJ, Lee B, Rohaan MW, Mangana J, Atkinson V, Zaman F, Young A, Hoeller C, Hersey P, Dummer R, Khattak MA, Millward M, Patel SP, Haydon A, Johnson DB, Lo S, Blank CU, Sandhu S, Carlino MS, Larkin JMG, Menzies AM, Long GV. Management of early melanoma recurrence despite adjuvant anti-PD-1 antibody therapy☆. Ann Oncol. 2020 Aug;31(8):1075-1082. doi: 10.1016/j.annonc.2020.04.471. Epub 2020 May 6.

    PubMed 32387454

  • Amaria RN, Prieto PA, Tetzlaff MT, Reuben A, Andrews MC, Ross MI, Glitza IC, Cormier J, Hwu WJ, Tawbi HA, Patel SP, Lee JE, Gershenwald JE, Spencer CN, Gopalakrishnan V, Bassett R, Simpson L, Mouton R, Hudgens CW, Zhao L, Zhu H, Cooper ZA, Wani K, Lazar A, Hwu P, Diab A, Wong MK, McQuade JL, Royal R, Lucci A, Burton EM, Reddy S, Sharma P, Allison J, Futreal PA, Woodman SE, Davies MA, Wargo JA. Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial. Lancet Oncol. 2018 Feb;19(2):181-193. doi: 10.1016/S1470-2045(18)30015-9. Epub 2018 Jan 18.

    PubMed 29361468

  • Eggermont AMM, Hamid O, Long GV, Luke JJ. Optimal systemic therapy for high-risk resectable melanoma. Nat Rev Clin Oncol. 2022 Jul;19(7):431-439. doi: 10.1038/s41571-022-00630-4. Epub 2022 Apr 25.

    PubMed 35468949

  • Huang AC, Orlowski RJ, Xu X, Mick R, George SM, Yan PK, Manne S, Kraya AA, Wubbenhorst B, Dorfman L, D'Andrea K, Wenz BM, Liu S, Chilukuri L, Kozlov A, Carberry M, Giles L, Kier MW, Quagliarello F, McGettigan S, Kreider K, Annamalai L, Zhao Q, Mogg R, Xu W, Blumenschein WM, Yearley JH, Linette GP, Amaravadi RK, Schuchter LM, Herati RS, Bengsch B, Nathanson KL, Farwell MD, Karakousis GC, Wherry EJ, Mitchell TC. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma. Nat Med. 2019 Mar;25(3):454-461. doi: 10.1038/s41591-019-0357-y. Epub 2019 Feb 25.

    PubMed 30804515

  • Long GV, Saw RPM, Lo S, Nieweg OE, Shannon KF, Gonzalez M, Guminski A, Lee JH, Lee H, Ferguson PM, Rawson RV, Wilmott JS, Thompson JF, Kefford RF, Ch'ng S, Stretch JR, Emmett L, Kapoor R, Rizos H, Spillane AJ, Scolyer RA, Menzies AM. Neoadjuvant dabrafenib combined with trametinib for resectable, stage IIIB-C, BRAFV600 mutation-positive melanoma (NeoCombi): a single-arm, open-label, single-centre, phase 2 trial. Lancet Oncol. 2019 Jul;20(7):961-971. doi: 10.1016/S1470-2045(19)30331-6. Epub 2019 Jun 3.

    PubMed 31171444

  • Patel SP, Othus M, Chen Y, Wright GP Jr, Yost KJ, Hyngstrom JR, Hu-Lieskovan S, Lao CD, Fecher LA, Truong TG, Eisenstein JL, Chandra S, Sosman JA, Kendra KL, Wu RC, Devoe CE, Deutsch GB, Hegde A, Khalil M, Mangla A, Reese AM, Ross MI, Poklepovic AS, Phan GQ, Onitilo AA, Yasar DG, Powers BC, Doolittle GC, In GK, Kokot N, Gibney GT, Atkins MB, Shaheen M, Warneke JA, Ikeguchi A, Najera JE, Chmielowski B, Crompton JG, Floyd JD, Hsueh E, Margolin KA, Chow WA, Grossmann KF, Dietrich E, Prieto VG, Lowe MC, Buchbinder EI, Kirkwood JM, Korde L, Moon J, Sharon E, Sondak VK, Ribas A. Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma. N Engl J Med. 2023 Mar 2;388(9):813-823. doi: 10.1056/NEJMoa2211437.

    PubMed 36856617

  • Blank CU, Lucas MW, Scolyer RA, van de Wiel BA, Menzies AM, Lopez-Yurda M, Hoeijmakers LL, Saw RPM, Lijnsvelt JM, Maher NG, Pulleman SM, Gonzalez M, Torres Acosta A, van Houdt WJ, Lo SN, Kuijpers AMJ, Spillane A, Klop WMC, Pennington TE, Zuur CL, Shannon KF, Seinstra BA, Rawson RV, Haanen JBAG, Ch'ng S, Naipal KAT, Stretch J, van Thienen JV, Rtshiladze MA, Wilgenhof S, Kapoor R, Meerveld-Eggink A, Grijpink-Ongering LG, van Akkooi ACJ, Reijers ILM, Gyorki DE, Grunhagen DJ, Speetjens FM, Vliek SB, Placzke J, Spain L, Stassen RC, Amini-Adle M, Lebbe C, Faries MB, Robert C, Ascierto PA, van Rijn R, van den Berkmortel FWPJ, Piersma D, van der Westhuizen A, Vreugdenhil G, Aarts MJB, Stevense-den Boer MAM, Atkinson V, Khattak M, Andrews MC, van den Eertwegh AJM, Boers-Sonderen MJ, Hospers GAP, Carlino MS, de Groot JB, Kapiteijn E, Suijkerbuijk KPM, Rutkowski P, Sandhu S, van der Veldt AAM, Long GV. Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma. N Engl J Med. 2024 Nov 7;391(18):1696-1708. doi: 10.1056/NEJMoa2402604. Epub 2024 Jun 2.

    PubMed 38828984

  • Kluger HM, Tawbi HA, Ascierto ML, Bowden M, Callahan MK, Cha E, Chen HX, Drake CG, Feltquate DM, Ferris RL, Gulley JL, Gupta S, Humphrey RW, LaVallee TM, Le DT, Hubbard-Lucey VM, Papadimitrakopoulou VA, Postow MA, Rubin EH, Sharon E, Taube JM, Topalian SL, Zappasodi R, Sznol M, Sullivan RJ. Defining tumor resistance to PD-1 pathway blockade: recommendations from the first meeting of the SITC Immunotherapy Resistance Taskforce. J Immunother Cancer. 2020 Mar;8(1):e000398. doi: 10.1136/jitc-2019-000398.

    PubMed 32238470

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ipilimumab and Nivolumab in people with Melanoma, run by University of Utah.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 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: withdrawn, as of the sponsor's last update on 19 Oct 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 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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Rate of pathologic response rate (pCR, mCR/nCR, or pPR) at the time of surgery. (time frame: 2 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 NCT06365619, which also lists 31 linked publications.

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 Oct 2026.

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