Inclusion Criteria:
- - Male/female participants who are at least 18 years of age on the day of signing
informed consent with histologically confirmed diagnosis of metastatic uveal
melanoma will be enrolled in this study.
- - Male participants must agree to use a contraception as detailed in Appendix 3 of
this protocol during the treatment period and for at least 120 days after the last
dose of Lenvatinib and refrain from donating sperm during this period.
- - Female participants are eligible to participate if she is not pregnant (see Appendix
3), not breastfeeding, and at least one of the following conditions applies:
1.
Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR. 2. A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during
the treatment period and for at least 120 days post pembrolizumab or post
Lenvatinib whichever occurs last.
- - The participant (or legally acceptable representative if applicable) provides
written informed consent for the trial.
- - Have measurable disease based on iRECIST.
Lesions situated in a previously
irradiated area are considered measurable if progression has been demonstrated in
such lesions.
- - Have provided archival tumor tissue sample or newly obtained core or excisional
biopsy of a tumor lesion not previously irradiated.
Formalin-fixed, paraffin
embedded (FFPE) tissue blocks are preferred to slides. If slides are only available,
ten slides would be required. Newly obtained biopsies are preferred to archived
tissue.
- - 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 first dose of study
intervention.
- - Have adequate organ function as defined in the following table (Table 2).
Specimens
must be collected within 7 days prior to the start of study intervention.
- - Subjects must agree to undergo paired fresh tumor biopsy specimens (to be collected
pre-treatment and day #15).
Subjects with tumor metastases that are not amenable to
image guided biopsies or who have a contraindication to biopsy (including but not
limited to anticoagulation therapy that cannot be interrupted for a biopsy) are
still eligible for participation in the clinical trial without undergoing biopsies.
Exclusion Criteria:
- - A WOCBP who has a positive serum pregnancy test within 24 hours prior to the first
dose of study intervention (see Appendix 3).
- - 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
(e.g., CTLA-4, OX 40, CD137).
Prior therapy with Tebentafusp is permitted. Prior
liver directed therapy is permitted (including but not limited to radioembolization,
chemoembolization, immunoembolization, radio-frequency ablation, external beam
radiation and resection).
- - Participants previously treated with radiation therapy must have recovered from all
radiation-related toxicities and not require corticosteroids.
- - Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug.
Administration of killed-virus vaccines and mRNA vaccines
are allowed.
- - Has 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 7 days prior to the first dose of study drug.
- - Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years.
Participants with basal cell carcinoma of the
skin, squamous cell carcinoma of the skin, early stage bladder cancer, or carcinoma
in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone
potentially curative therapy are not excluded.
- - Has known active CNS metastases and/or carcinomatous meningitis.
Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening),
clinically stable and without requirement of steroid treatment for at least 14 days
prior to first dose of study intervention.
- - Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients.
- - Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs).
Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- - Has a history of (non-infectious) pneumonitis/interstitial lung disease that
required steroids or has current pneumonitis/interstitial lung disease.
- - Has an active infection requiring systemic therapy.
- - 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.
- - Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
- - 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.
- - Has had an allogenic tissue/solid organ transplant.
- - Uncontrolled blood pressure (Systolic BP>140 mmHg or diastolic BP >90 mmHg) in spite
of an optimized regimen of antihypertensive medication.
- - Electrolyte abnormalities that have not been corrected.
- - Significant cardiovascular impairment: history of congestive heart failure greater
than New York Heart Association (NYHA) Class II, unstable angina, myocardial
infarction or stroke within 6 months of the first dose of study drug, or cardiac
arrhythmia requiring medical treatment at Screening.
- - Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage.
The
degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery)
should be considered because of the potential risk of severe hemorrhage associated
with tumor shrinkage/necrosis following lenvatinib therapy.
- - Subjects having ≥2+ proteinuria on urine dipstick testing.
However, subjects with
≥2+ proteinuria on urine dipstick testing may undergo a 24-hour urine collection for
quantitative assessment of proteinuria. Subjects with <1 g/24-hour proteinuria are
eligible for participation.
- - Subjects who have not recovered adequately from any toxicity from other anti- cancer
treatment regimens and/or complications from major surgery prior to starting
therapy.
Withhold lenvatinib for at least 1 week prior to elective surgery. Do not
administer for at least 2 weeks following major surgery and until adequate wound
healing.
- - Females who are breastfeeding or pregnant at Screening or Baseline (as documented by
a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic
gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units
of ß-hCG [or hCG]).
- - Females of child-bearing potential must be willing to use effective contraception
during study and for 120 days after the last dose.
- The participant has severe hypersensitivity (≥Grade 3) to lenvatinib and/or any of
its excipients
