Clinical trial NCT05545969: Neoadjuvant Pembrolizumab and Lenvatinib for Mucosal Melanoma
Official title: A Multicentre, Open Label, Phase II Study to Determine the Response to Neoadjuvant Pembrolizumab and Lenvatinib Followed by Adjuvant Treatment With Pembrolizumab and Lenvatinib in Mucosal Melanoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Mucosal Melanoma
Keywords: Immunotherapy
VEGF inhibitor
Neoadjuvant
Adjuvant
Pembrolizumab
Lenvatinib
Pathlogical respone
Lead sponsor: Melanoma Institute Australia
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2022-09-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Multicentre, open label, clinical trial
Primary purpose: TREATMENT

Brief summary: In many cancers, early stage diagnosis and early treatment offers the best chance of a prolonged recurrence free- and overall survival. Neoadjuvant immunotherapy involves administering immune checkpoint inhibitors before surgical resection in high-risk resectable disease, such as mucosal melanoma. In resectable cancers, immune checkpoint inhibitors can enhance anti-tumour immunity by exploiting a competent immune system prior to surgery. Activating antigen-specific T cells found in the primary or baseline tumour continue to exert anti-tumour effects on remaining neoplastic cells after the resection of the original tumour, potentially preventing recurrences from occurring.

In resectable mucosal melanoma, an opportunity exists to improve clinical outcomes with the addition of neoadjuvant and adjuvant systemic therapy with nivolumab and lenvatinib as an adjunct to surgery.


Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Histologically confirmed diagnosis of fully-resectable mucosal melanoma
* Pathological ± clinical confirmation that the presenting lesion(s) does not represent metastasis from an unknown primary cutaneous or ocular melanoma
* Measurable disease per RECIST
* Availability of a newly obtained core or excisional biopsy of an affected lesion which has not been previously irradiated
* Ability to swallow and retain oral medication
* ECOG 0 - 1
* Adequate organ function per laboratory values
* Adequately controlled blood pressure with or without anti-hypertensive medications, defined as ≤ 150/90 mmHg at screening
* Anticpated life expectabcy of \> 12 months.

Exclusion Criteria:

* A diagnosis of uveal or cutaneous melanoma
* A WOCBP who has a positive serum pregnancy test within 72 hours prior to starting study treatment
* Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor for any disease
* Prior systemic treatment for mucosal melanoma including investigational agents. Prior surgery is acceptable
* Major surgery within 3 weeks prior to first dose of lenvatinib
* Patients who have not recovered adequately from any toxicity from other permitted anti- cancer treatment regimens
* Prior radiotherapy within 2 weeks of start of study treatment
* Received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study treatment
* Patient is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
* A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study treatment
* Active autoimmune disease that has required systemic treatment in the past 12 months
* Known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has known central nervous system metastases and/or carcinomatous meningitis
* A history of (non-infectious) pneumonitis//interstitial lung disease that required steroids or has current pneumonitis or current interstitial lung disease
* Active infection requiring systemic therapy
* Known history of Human Immunodeficiency Virus, active Hepatitis B or C
* Has a known history of active TB
* A current diagnosis of any gastrointestinal condition that might affect the absorption of lenvatinib
* Has a pre-existing ≥ Grade 3 gastrointestinal adverse event or a non-gastrointestinal fistula
* Prolonged QT interval \>480 ms
* History of, or current cardiovascular disease
* Has a history of, or a current bleeding or thrombotic disorders or patients at risk for severe haemorrhage
* Active haemoptysis
* Patients with a ≥2+ (≥100 mg/dL) proteinuria on urine dipstick testing
* Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study
* Has had an allogenic tissue/solid organ transplant.

Primary outcomes:
measure: Change in immune cell expression of HIF1 and immune cell densities
timeFrame: Baseline, week 1 week 6
measure: Pathological response rate
timeFrame: 6 weeks
Secondary outcomes:
measure: RECIST response rate
timeFrame: 6 weeks
Other outcomes:
measure: PERCIST metabolic response rate
timeFrame: 6 weeks
measure: Immune-related response criteria
timeFrame: 6 weeks
measure: Event-free survival
timeFrame: 10 years
measure: Recurrence-free survival
timeFrame: 10 years
measure: Overall survival
timeFrame: 10 years
measure: Incidence of any treatment-emergent adverse events
timeFrame: 52 weeks
measure: Surgical outcomes
timeFrame: 6 weeks
measure: Patient reported quality of life measures
timeFrame: 52 weeks
measure: Gut microbiome influence on response outcomes
timeFrame: 52 weeks
measure: Concordance of INMC-rated pathological response with with RECIST response, PERCIST response and immune-related response crtieria.
timeFrame: 6 weeks
Locations:
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia
state: New South Wales
Study officials:
affiliation: Melanoma Institute Australia
name: Georgina Long, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References: