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

Inclusion Criteria: * 1\. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial. * 2\. Male/female participants who are at least 18 years of age on the day of signing informed consent. * 3\. 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". * 4\. 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. * 5\. 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. * 6\. Able to swallow and retain oral medication. * 7\. 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. * 8\. 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. * 9\. 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. * 10\. Have adequate organ function as defined by routine laboratory testing. * 11\. Adequately controlled blood pressure, with or without anti-hypertensive medications, defined as ≤ 150/90 mmHg at screening and no change in anti-hypertensive medications within one week of the first dose of study treatment. Note: Patients who are taking ≥ 3 anti-hypertensive medications at baseline will require approval from the Lead Investigator prior to enrolment. * 12\. Anticipated life expectancy of \> 12 months. Exclusion Criteria: * 1\. 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. * 2\. 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. * 3\. 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. * 4\. 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. * 5\. Participants who have not recovered adequately from any toxicity from other anti- cancer treatment regimens. * 6\. 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. * 7\. 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. * 8\. 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. * 9\. 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, * Psoriasis not requiring systemic treatment, * Autoimmune conditions which are not expected to recur in the absence of an external trigger. * 10\. Has active autoimmune disease that has required systemic treatment in the past 12 months (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). The following are permitted: * Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc, Inhaled or intranasal corticosteroids (with minimal systemic absorption) may be continued if patient on a stable dose, * Non-absorbed intra-articular steroid injections are permitted. * 11\. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. The following malignancies, if undergone successful definitive resection or curative treatment, are permitted: * Basal cell carcinoma of the skin * Squamous cell carcinoma of the skin * Carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy) * Prostatic intraepithelial neoplasia * In situ melanoma * Atypical melanocytic hyperplasia * Multiple primary melanomas * Other malignancies for which the patient has been disease free for 1 year. * 12\. Has known CNS metastases and/or carcinomatous meningitis. * 13\. Has severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients. * 14\. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis or current interstitial lung disease. * 15\. Has an active infection requiring systemic therapy. * 16\. Has a known history of Human Immunodeficiency Virus (HIV). * 17\. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as HCV RNA \[qualitative\] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority. * 18\. Has a known history of active TB (Bacillus Tuberculosis). * 19\. Current diagnosis of any gastrointestinal condition that might affect the absorption of lenvatinib (e.g. malabsorption syndrome, gastrointestinal anastomosis, bariatric surgery). * 20\. Has a pre-existing ≥ Grade 3 gastrointestinal or non-gastrointestinal fistula. * 21\. History of, or current cardiovascular disease including: Uncontrolled arrhythmias associated with haemodynamic instability, Uncontrolled arrhythmias requiring medical treatment at screening, Unstable angina within 6 months of the first dose of study drug, myocardial infarction within 6 months of the first dose of study drug * \>NYHA grade 2 congestive cardiac failure * Uncontrolled and treatment refractory hypertension systolic \> 150 mmHg and/or diastolic \> 90 mmHg in spite of an optimized regimen of antihypertensive medication(s). * Cerebrovascular accident within 6 months of the first dose of study drug * 22\. Has a history of, or a current bleeding or thrombotic disorders or participants at risk for severe haemorrhage. The degree of tumour invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe haemorrhage associated with tumour shrinkage/necrosis following lenvatinib therapy. * 23\. Participants with a \>1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is \<1 g/24 hours. * 24\. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. * 25\. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * 26\. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.