WithdrawnNCT05545969Neo PeLeMMUpdated Jun 26, 2024

Neoadjuvant Pembrolizumab and Lenvatinib for Mucosal Melanoma

A Phase 2 interventional study of Pembrolizumab and Lenvatinib in Mucosal Melanoma, sponsored by Melanoma Institute Australia. Withdrawn at 1 site in Australia. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2024-06-26.

Sponsored by Melanoma Institute Australia · Phase 2, Interventional, and Treatment

Why this study was withdrawn

Insufficient funding

Phase: Phase 2
Study type: Interventional
Enrollment: 0
Allocation: Not applicable
Ages: 18 Years to 100 Years
Sex: All

Study 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.

Conditions studied

Mucosal Melanoma

Browse trials for

Melanoma 3,005

Keywords

Immunotherapy
VEGF inhibitor
Neoadjuvant
Adjuvant
Pembrolizumab
Lenvatinib
Pathlogical respone

In context

Melanoma

3,005 studies on the registry are indexed under Melanoma; 519 are open to participants now.

Browse Melanoma studies →

Lead sponsor

Melanoma Institute Australia is the lead sponsor of 16 studies on the registry; 7 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 100 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 0 participants (actual)

Study arms

Experimental
Neoadjuvant and Adjuvant Therapy
Neoadjuvant pembrolizumab \& lenvatinib for 6 weeks followed by definitive surgery then adjuvant pembrolizumab alone for 46 weeks
Drug: Pembrolizumab · Drug: Lenvatinib

Interventions

DrugPembrolizumab
Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Also known as: Keytruda
DrugLenvatinib
Lenvatinib is an oral potent multiple RTK inhibitor that selectively inhibits VEGF receptors, VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4), fibroblast growth factor receptor (FGFR1-4), platelet derived growth factor (PDGFRα), stem cell factor receptor (KIT), and rearranged during transfection (RET)
Also known as: Lenvima

What researchers measure

Primary outcomes

Change in immune cell expression of HIF1 and immune cell densities
Tumour and immune cell expression of HIF1a and immune cell densities will be compared between baseline and day 8 melanoma tissue biopsies.
Time frame: Baseline, week 1 week 6
Pathological response rate
Proportion of patients with complete absence of residual melanoma cells in the the planned resected tumour site(s) at week 6 surgery
Time frame: 6 weeks

Secondary outcomes

RECIST response rate
Proportion of patients with a complete or partial RECIST response; patients with no RECIST response and patients who have RECIST confirmed disease progression in the neoadjuvant period.
Time frame: 6 weeks

Other outcomes

PERCIST metabolic response rate
Proportion of patients with a complete metabolic resolution (complete resolution of 18F-FDG uptake within the tumour volume); partial metabolic response (reduction of a minimum of 30% in tumour SUV normalised by lean body mass \[SUL\]; stable metabolic response (neither CR, PR or PD) and progressive metabolic disease (an increase of 30% in tumour SUL peak or the appearance of new lesions) in the neoadjuvant period
Time frame: 6 weeks
Immune-related response criteria
Proportion of patients with a complete or partial immune related response; patients with no response and patients who have confirmed disease progression in the neoadjuvant period
Time frame: 6 weeks
Event-free survival
Proportion of patients with either of: progression of disease prior to surgery or which precludes surgery, local or distant disease recurrence, mucosal melanoma related death and treatment related death, whichever occurs first from the first dose of neoadjuvant treatment or from surgery (disease recurrence).
Time frame: 10 years
Recurrence-free survival
Proportion of patients who are recurrence-free at yearly time points from the date of definitive surgery and from the end of adjuvant treatment until the end of 5 years from C1D1. To include time to any recurrence, new primary disease, locoregional recurrence and distant recurrence.
Time frame: 10 years
Overall survival
Proportion of patients alive at yearly time points from the date of first neoadjuvant study treatment (C1D1) until the end of 5 years follow up.
Time frame: 10 years
Incidence of any treatment-emergent adverse events
* Number, grade and duration of drug related adverse events across different grades, with attribution to pembrolizumab, lenvatinib or both. * Number, grade and duration of drug related adverse events requiring an interruption or permanent discontinuation of pembrolizumab, lenvatinib or both. * The completion rate of scheduled pembrolizumab, lenvatinib or both (administered doses / scheduled doses).
Time frame: 52 weeks
Surgical outcomes
The rate of surgical complications during and following definitive surgery
Time frame: 6 weeks
Patient reported quality of life measures
The change in longitudinal quality of life individual and overall scores from baseline.
Time frame: 52 weeks
Gut microbiome influence on response outcomes
To correlate gastrointestinal mucosal integrity with bacterial composition in stool samples, clinical outcomes.
Time frame: 52 weeks
Concordance of INMC-rated pathological response with with RECIST response, PERCIST response and immune-related response crtieria.
Concordance of pathological response with RECIST response, PERCIST response and immune-related response crtieria.
Time frame: 6 weeks

Study locations

1 site

Melanoma Institute Australia
Wollstonecraft, New South Wales 2065, Australia

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 26, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT05545969
Lead sponsor: Melanoma Institute Australia
Collaborators: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Sep 19, 2022
Start date: Mar 2024 (estimated)
Primary completion: May 2026 (estimated)
Completion: May 2036 (estimated)
Last update: Jun 26, 2024

Study contacts

Georgina Long, MBBS, PhD

principal investigator · Melanoma Institute Australia

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is withdrawn, as verified in Jun 2024. You cannot join it, but the record below documents what was studied.

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