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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Melanoma
• Intervention / Treatment: Drug: Ipilimumab; Drug: Nivolumab

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Kaitlin Stephens; Phone Number: 801-213-8494; Email: kaitlin.stephens@hci.utah.edu

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 while receiving or within 3 months of completion of adjuvant anti-PD1 therapy.
• ECOG Performance Status ≤ 1.

• Adequate organ function as defined as:

  • Hematologic:

    • 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 as described in Section 5.3.1.
• Subject has adequate archival tissue or agrees to undergo a fresh tissue biopsy if sufficient archival tissue is unavailable.
• 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.

Exclusion Criteria:

• 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.
• 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.

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: Treatment: All Patients; Neoadjuvant Ipilimumab and Nivolumab	Drug: Ipilimumab; Two cycles of neoadjuvant ipilimumab prior to surgical resection.; Drug: Nivolumab; two cycles of neoadjuvant nivolumab prior to surgical resection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 that have recurred while receiving/recently completed adjuvant anti-PD1 therapy.	2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2 months
Rate of adverse events that occur within 30 days post-surgery.	Assess the impact of neoadjuvant ipi/nivo on morbidity of definitive surgery.	30 days
Rate of Event Free Survival (EFS).	Assess EFS in the study population.	11 years
Rate of Overall Survival (OS).	Assess OS in this study population.	11 years
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.	11 years

Collaborators and Investigators

• Sponsor: University of Utah
• Investigators: Principal Investigator: John Hyngstrom, MD, Huntsman Cancer Institute

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: April 9, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Estimated): April 15, 2024

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Ipilimumab
• Other Study ID Numbers: HCI168525

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No