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
