Neoadjuvant Pembrolizumab and Lenvatinib for Mucosal Melanoma

NCT05545969 | Withdrawn Phase 2 DMC

• 1 other identifier: MIA2022/442
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Mucosal Melanoma

Keywords

Immunotherapy; VEGF inhibitor; Neoadjuvant; Adjuvant; Pembrolizumab; Lenvatinib; Pathlogical respone

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  6 weeks

Secondary Outcomes (1)

• RECIST response rate

  6 weeks

Other Outcomes (10)

• PERCIST metabolic response rate

  6 weeks

• Immune-related response criteria

  6 weeks

• Event-free survival

  10 years

Study Arms (1)

Neoadjuvant and Adjuvant Therapy

EXPERIMENTAL

Neoadjuvant pembrolizumab \& lenvatinib for 6 weeks followed by definitive surgery then adjuvant pembrolizumab alone for 46 weeks

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

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

Neoadjuvant and Adjuvant Therapy

Lenvatinib DRUG

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

Neoadjuvant and Adjuvant Therapy

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Melanoma Institute Australia: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Melanoma Institute Australia

Wollstonecraft, New South Wales, 2065, Australia

Location

MeSH Terms

Interventions

pembrolizumab; lenvatinib

Study Officials

• Georgina Long, MBBS, PhD

  Melanoma Institute Australia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentre, open label, clinical trial

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: September 19, 2022
• Study Start: March 1, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2036
• Last Updated: June 26, 2024

Record last verified: 2024-06

Locations

AU (1)