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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05545969




Registration number
NCT05545969
Ethics application status
Date submitted
6/09/2022
Date registered
19/09/2022
Date last updated
30/01/2024

Titles & IDs
Public title
Neoadjuvant Pembrolizumab and Lenvatinib for Mucosal Melanoma
Scientific 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
Secondary ID [1] 0 0
MIA2022/442
Universal Trial Number (UTN)
Trial acronym
Neo PeLeMM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mucosal Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Lenvatinib

Experimental: Neoadjuvant and Adjuvant Therapy - Neoadjuvant pembrolizumab & lenvatinib for 6 weeks followed by definitive surgery then adjuvant pembrolizumab alone for 46 weeks


Treatment: Drugs: 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.

Treatment: Drugs: 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 (PDGFRa), stem cell factor receptor (KIT), and rearranged during transfection (RET)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in immune cell expression of HIF1 and immune cell densities
Timepoint [1] 0 0
Baseline, week 1 week 6
Primary outcome [2] 0 0
Pathological response rate
Timepoint [2] 0 0
6 weeks
Secondary outcome [1] 0 0
RECIST response rate
Timepoint [1] 0 0
6 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/03/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2036
Actual
Sample size
Target
44
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Melanoma Institute Australia - Wollstonecraft
Recruitment postcode(s) [1] 0 0
2065 - Wollstonecraft

Funding & Sponsors
Primary sponsor type
Other
Name
Melanoma Institute Australia
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Merck Sharp & Dohme LLC
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05545969
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Georgina Long, MBBS, PhD
Address 0 0
Melanoma Institute Australia
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Georgina Long, MBBS, PhD
Address 0 0
Country 0 0
Phone 0 0
+612 9911 7200
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05545969