NeoAdjuvant, Spare-Adjuvant (NASA) in Stage IIIB-IV (M1a) Melanoma

Phase 2Not Yet RecruitingNCT07740941

UNC Lineberger Comprehensive Cancer Center55 enrolled

Overview

This study evaluates the impact of neoadjuvant Programmed cell death Protein 1 (PD-1)-based treatment regimens in patients with resectable stage IIIB-M1a cutaneous or unknown primary melanoma at high risk of relapse without adjuvant therapy after definitive lymphadenectomy and irrespective of pathologic response outcome on the 2-year overall survival (OS). It was hypothesized that neoadjuvant PD1 inhibitor-based treatment without adjuvant treatment does not significantly (non-inferior) impact OS in this study patient population. Patients will be randomized to either two infusions of pembrolizumab or one infusion of ipilimumab plus nivolumab followed by a single infusion of nivolumab. Patients will undergo follow-up and restaging scans to assess event-free survival at 12 months and OS at 24 months after the first neoadjuvant treatment infusion.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Melanoma (Skin Cancer)Melanoma Stage Stage IIIB Melanoma Stage M1

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Written informed consent will be obtained to participate in the study, and HIPAA authorization for the release of personal health information. * Subject is willing and able to comply with study procedures based on the judgment of the investigator or protocol designee, including randomization. * Age ≥ 18 years at the time of consent. * ECOG Performance Status of 0-2. * Histological confirmation of cutaneous melanoma or melanoma of unknown primary. * AJCC stage IIIB/IVa resectable disease that is measurable by iRECIST criteria. * Adequate hematologic, renal, hepatic, and heart function Exclusion Criteria: * Prior treatment with PD-1 Programmed cell death Protein 1 (PD-1) and Cytotoxic T-lymphocyte Antigen 4 (CTLA-4). * Has an active autoimmune disease that requires systemic treatment with the use of disease-modifying agents or immunosuppressive drugs. For corticosteroids, up to 10 mg of prednisone daily, or an equivalent dose, is permitted. Hormone replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. * Any condition, including laboratory abnormalities, that, in the opinion of the investigator, places the subject at unacceptable risk if he/she were to participate in the study. This includes, but is not limited to, serious medical conditions or psychiatric illnesses that are likely to interfere with participation in this clinical study.

Outcomes

Primary Outcomes

Overall survival

The overall survival (OS) rate will be defined from the initiation of study treatments for the combined patient cohorts (cohort A and cohort B).

Time frame: 2-year

Secondary Outcomes

Event - Free Survival (EFS)

The Event - Free Survival (EFS) rate will be defined from the initiation of study treatments for the combined patient cohorts (cohort A and cohort B).

Time frame: 1-year

Major pathologic response (MPR) rate

The MPR rate for each of the two study treatment cohorts (cohort A and cohort B) will be defined using established pathologic response criteria. Pathologic response will be assessed by determining the percentage of residual viable tumor in the resected specimen. Major pathologic response is defined as ≤10% residual viable tumor, and pathologic complete response is defined as the absence of viable tumor cells.

Time frame: Up to 12 weeks

Treatment Related Adverse Events (TRAEs)

TRAEs are defined as adverse events assessed by the investigator as related to study treatment, Grade 3 or higher grades. The incidence of TRAEs will be determined separately for each of the two cohorts and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 6.0. CTCAE classifies severity as follows: Grade 1 - asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 - minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL). Grade 3 - severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 - life-threatening consequences; urgent intervention indicated. Grade 5 - death related to the adverse event.