A Study to Evaluate Adaptive Dosing of Ipilimumab and Nivolumab Combination Immunotherapy

A Phase II Study to Evaluate Adaptive Dosing of Ipilimumab and Nivolumab Combination Immunotherapy

This study will help determine whether 2 doses of the combination (ipilimumab + nivolumab) is sufficient for patients with early benefit compared to the usual way of trying to give 4 doses. If patients do not show early benefit after 2 doses, patients will be able to continue with additional ipilimumab + nivolumab, even beyond the standard 4 doses if felt in the best interest of the patient.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Melanoma
• Intervention / Treatment: Drug: ipilimumab; Drug: nivolumab

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Healthcare Alliance (Data collection only)
    • Hartford, Connecticut, United States, 06102
      • Jaykumar Thumar
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • JOHNS HOPKINS HOSPITAL (Data Analysis Only)
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital (Data and Specimen Analysis Only)
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Memorial Sloan Kettering Basking Ridge
    • Middletown, New Jersey, United States, 07748
      • Memorial Sloan Kettering Monmouth
    • Montvale, New Jersey, United States, 07645
      • Memorial Sloan Kettering Bergen
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Westchester
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10021
      • Hospital for Special Surgery (Data Analysis)
    • New York, New York, United States, 10032
      • Columbia University (Data Analysis Only)
    • Uniondale, New York, United States, 11553
      • Memorial Sloan Kettering Nassau
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network (Data Collection Only)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologic diagnosis of unresectable III or stage IV metastatic melanoma.
• Subjects must have at least 1 extracranial, unresectable, non-bony lesion that is measurable radiographically (based on RECIST 1.1).
• No prior CTLA-4 or PD-1/PD-L1 therapy for the treatment of metastatic disease.
• ECOG performance status of 0-1.
• Life expectancy ≥ 4 months.

• Screening laboratory parameters:

  • White blood cell (WBC) count ≥ 2000/μL;
  • Absolute neutrophil count (ANC) ≥ 1500/μL;
  • Platelets ≥ 100,000/μL;
  • Hemoglobin (Hgb) ≥ 9 g/dL;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN);
  • Total bilirubin ≤ 1.5 × ULN (< 3 mg/dL for subjects with Gilbert's disease);
  • Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): Female CrCl = [(140 - age in years) x weight in kg x 0.85] / [72 x serum creatinine in mg/dL] Male CrCl = [(140 - age in years) x weight in kg x 1.00] / [72 x serum creatinine in mg/dL]
• Age ≥ 18 years.
• Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of effective contraception from screening, and must agree to continue using such precautions for 23 weeks after the final dose of investigational product; cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control.

[Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined as 12 months with no menses without an alternative medical cause).] Nonsterilized males who are sexually active with a female partner of childbearing potential must use 2 acceptable methods of effective contraception from Day 1 and for 31 weeks after receipt of the final dose of investigational product.

Acceptable methods of effective contraception are described in the following table:

• Barrier Methods - Male condom plus spermicide, cap plus spermicide, or diaphragm plus spermicide.
• Intrauterine Device Methods-Copper T, or Levonorgestrel-releasing intrauterine system (e.g., Mirena®), also considered a hormonal method.
• Hormonal Methods-Implants, hormone shot or injection, combined pill, minipilimumabll, or Patch.

Exclusion Criteria:

• Active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (>10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• History of motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre Syndrome, Myasthenia Gravis).
• Other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the investigator.
• Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C infection. Antibody to Hepatitis B or C without evidence of active infection may be allowed.
• History of severe allergic reactions to any unknown allergens or any components of the study drugs.
• Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
• Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
• Lack of availability for immunological and clinical assessments or post-study follow-up contact to determine relapse and survival.
• Women who are breastfeeding or who are pregnant as evidenced by a positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) performed within 14 days of the first dose of study drug and by a urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours of the first dose of study drug(s).
• Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ipilimumab and nivolumab; Pts will receive 2 doses of ipilimumab 3mg/kg + nivolumab 1mg/kg every 3 weeks. Week 6, if pts have achieved a favorable antitumor effect by RECIST will begin maintenance nivolumab alone at 480mg every 4 weeks for 2 doses (week 6 & week 10) & repeat response assessments at week 12. If pts don't achieve a favorable antitumor effect at week 6, pt will get 2 additional doses of ipilimumab + nivolumab every 3 weeks & then will be assessed for response at week 12. If pts haven't achieved a favorable antitumor effect by week 12, if felt in the best interest for the pt as determined by the PI, pts may continue getting additional doses of ipilimumab + nivolumab with response reassessments after every 2 doses. Maintenance nivolumab will continued until unacceptable toxicity or confirmed disease progression. If pts have had an initial clinical benefit from therapy & subsequently experience progressive disease at any time, reinduction with combination ipilimuma+ nivolumab will be allowed.

Drug: ipilimumab; ipilimumab 3mg/kg; Drug: nivolumab; nivolumab 1mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	RECIST 1.1.	at 6 weeks

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Michael Postow, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

General Publications

• Postow MA, Goldman DA, Shoushtari AN, Betof Warner A, Callahan MK, Momtaz P, Smithy JW, Naito E, Cugliari MK, Raber V, Eton O, Nair SG, Panageas KS, Wolchok JD, Chapman PB. Adaptive Dosing of Nivolumab + Ipilimumab Immunotherapy Based Upon Early, Interim Radiographic Assessment in Advanced Melanoma (The ADAPT-IT Study). J Clin Oncol. 2022 Apr 1;40(10):1059-1067. doi: 10.1200/JCO.21.01570. Epub 2021 Dec 20.
• Pandit-Taskar N, Mauguen A, Frosina D, Jungbluth A, Busam KJ, Lyashchenko S, Schwartz J, Momtaz P, Warner AB, Smithy JW, Shoushtari AN, Callahan MK, Chapman PB, Postow MA. Programmed death ligand-1 PET imaging in patients with melanoma: a pilot study. Melanoma Res. 2025 Oct 1;35(5):328-338. doi: 10.1097/CMR.0000000000001050. Epub 2025 Jun 25.

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2017
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: April 18, 2017
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 20, 2017

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Nivolumab; Ipilimumab; unresectable; III or stage IV; 17-162
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; Ipilimumab
• Other Study ID Numbers: 17-162

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes