Neoadjuvant Pembrolizumab and Lenvatinib for Mucosal Melanoma

NCT ID: NCT05545969

Last Updated: 2024-06-26

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-31
• Study Completion Date: 2036-05-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant and Adjuvant Therapy

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

Group Type: EXPERIMENTAL

Pembrolizumab

Intervention Type: 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.

Lenvatinib

Intervention Type: 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)

Interventions

Pembrolizumab

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.

Intervention Type: DRUG

Lenvatinib

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)

Intervention Type: DRUG

Other Intervention Names

Keytruda; Lenvima

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Melanoma Institute Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Georgina Long, MBBS, PhD

Role: PRINCIPAL_INVESTIGATOR

Melanoma Institute Australia

Locations

Melanoma Institute Australia

Wollstonecraft, New South Wales, Australia

Countries

Australia

Other Identifiers

MIA2022/442

Identifier Type: -

Identifier Source: org_study_id