A Phase II Study of Neoadjuvant Pembrolizumab & Lenvatinib for Resectable Stage III Melanoma

NCT04207086 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: MIA/CT2019/281OTSP 57111
• Study Type: interventional
• Target: 21
• 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. In stage III/IV resectable melanoma, an opportunity exists to improve outcomes with the addition of neoadjuvant and adjuvant systemic therapy as an adjunct to surgery. Neoadjuvant clinical trials for resectable but bulky stage III/IV melanoma allows for the efficient and rapid evaluation of drug activity in humans utilising multiple clinical endpoints of metabolic, radiological and pathological response; relapse-free survival; overall survival.

Conditions

Melanoma Stage III

Keywords

Neoadjuvant therapy; Adjuvant therapy; Pembrolizumab; Lenvatinib; Pathological response; RECIST response; Metabolic response; Translational research

Outcome Measures

Primary Outcomes (2)

• 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.

  From baseline to 6 weeks planned resected tumour site(s) at week 6 surgery

• The anti-tumoural immune response

  Changes in T cell tumour infiltration, tumour PD-L1 expression, melanoma antigen expression, presence of regulatory T cells, immunosuppressive cytokines, VEGF signalling and modulation of the tumour vasculature.

  Baseline, week 1 week 6

Secondary Outcomes (20)

• Objective clinical (RECIST) response rate

  From baseline to 6 weeks

• Metabolic response rate

  From baseline to 6 weeks

• Relapse free survival

  10 years

• Treatment free survival

  1, 2, 3, 4, 5 and 10 years from the end of adjuvant treatment

• Overall survival

  10 years

Other Outcomes (4)

• Concordance of immune related response criteria (irRC) with RECIST response

  Weeks 6 and 52

• Correlation of the gut microbiome with RECIST response to immunotherapy

  Baseline, Week 6, week 24, at relapse if this occurs within 10 years from study entry

• Correlation of intestinal permeability with treatment response and toxicity

  Baseline and during 52 weeks of treatment

Study Arms (1)

6 wk pembrolizumab & lenvatinib, surgery, 46 wk pembrolizumab

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

6 wk pembrolizumab & lenvatinib, surgery, 46 wk pembrolizumab

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

6 wk pembrolizumab & lenvatinib, surgery, 46 wk pembrolizumab

Eligibility Criteria

• Age: 18 Years - 115 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• \. Male/female participants who are at least 18 years of age on the day of signing informed consent.
• \. Histologically confirmed diagnosis of resectable AJCC (8th edition) Stage IIIB, IIIC or IIID cutaneous or unknown primary melanoma (except for any in-transit or satellite metastases) will be enrolled in this study. Note:
• At baseline, patients may have a primary melanoma in addition to nodal disease.
• At baseline, there must be sufficient nodal +/- primary disease which is amenable to multiple excision or core biopsies biopsies.
• "Resectable" disease is defined as having no significant vascular, central nervous system or bony involvement. Only cases where a complete surgical resection leading to tumour free margins and which is safely achieved is considered "resectable".
• \. Have measurable disease based on RECIST version 1.1 criteria: ≥ 10mm in the longest diameter for primary (if applicable) lesions and ≥ 15mm in the shortest diameter for lymph nodes.
• \. Have provided a newly obtained core or excisional biopsy of an affected lymph node lesion which has been not previously irradiated. Archival tissue from the primary melanoma (if applicable) will also be collected, if available, but is not a requirement for study entry.
• \. Able to swallow and retain oral medication.
• \. A male participant must agree to use a contraception during the treatment period and for at least and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period and for at least 120 days after the last dose.
• \. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP), OR
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least and for at least 120 days after the last dose of study treatment.
• \. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the date of first dose of study treatment.
• \. Have adequate organ function as defined by routine laboratory testing.

You may not qualify if:

• \. A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• \. Has received 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.
• \. Has received prior treatment for melanoma including investigational agents within 4 weeks prior to first dose of study treatment. The following are permitted:
• Surgery for primary or past stage III melanoma.
• Prior adjuvant interferon or ipilimumab for resected stage II/III melanoma and have recovered to ≤ Grade 1 or baseline from any treatment related adverse effects.
• \. Has had major surgery within 3 weeks prior to first dose of study treatments. Note: adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
• \. Participants who have not recovered adequately from any toxicity from other anti- cancer treatment regimens.
• \. Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. Prior radiotherapy to the presenting tumour is prohibited.
• \. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• \. 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. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• \. Has a diagnosis of immunodeficiency and 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 drug. The following are permitted:
• Vitiligo,
• Type I diabetes mellitus,
• Residual autoimmune hypothyroidism on stable hormone replacement,
• Resolved childhood asthma or atopy,

Sponsors & Collaborators

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

Study Sites (1)

Melanoma Institute Australia

North Sydney, New South Wales, 2060, Australia

Location

MeSH Terms

Conditions

Melanoma

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Georgina V Long

  Melanoma Institute Australia

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: December 17, 2019
• First Posted: December 20, 2019
• Study Start: November 11, 2020
• Primary Completion: January 31, 2023
• Study Completion (Estimated): January 1, 2033
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)