• Ability to comply with the study protocol, in the investigator's judgment

• Histologically or cytologically confirmed solid tumors (cutaneous melanoma, non-small cell lung cancer, renal cell carcinoma, endometrial cancer, ovarian cancer, MSI-H solid tumors (deficient mismatch repair system or other solid tumors) that have progressed on or refractory to standard of care therapies for their disease

• Phase I dose escalation phase

‣ Advanced metastatic or recurrent solid tumors (where pembrolizumab is approved and/or have shown efficacy) that have progressed on or refractory to standard of care therapies for their disease

⁃ Prior anti-PD1 or PDL1 therapy is allowed

⁃ Prior anti-CTLA4 therapy is allowed if had anti-CTLA4 free interval of 6 months or more

⁃ At least one prior line of therapy in the dose escalation phase

• Phase Ib dose expansion cohorts

‣ Platinum-resistant recurrent ovarian cancer (recurred within 6 months or less of prior platinum therapy) or post-PD1/PDL1 MSI-H cancers (mismatch repair deficient tumors). Patients in the ovarian cancer cohort must have received chemotherapy plus bevacizumab unless bevacizumab is contra-indicated or considered risky per treating physician.

⁃ Prior 1-5 lines of therapy for dose expansion

⁃ Prior anti-PD1/PDL1 therapy is allowed in the MSI-H cohort but not in the ovarian cohort

⁃ Prior anti-CTLA4 therapy is not allowed.

⁃ Primary platinum- refractory cancers are excluded in the dose expansion (progressed during or within 3 months of primary platinum therapy)

• Measurable disease per RECIST v1.1

• o Previously irradiated lesions can be considered as measurable disease only if progressive disease has been unequivocally documented at that site since radiation.

• Availability of a representative tumor specimen for exploratory biomarker research

• ECOG Performance Status of 0-1

• Life expectancy ≥ 6 months

• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of study treatment:

‣ ANC ≥ 1.5 × 109/L (1500/L) without granulocyte colony-stimulating factor support

⁃ Platelet count ≥ 100 × 109/L (100,000/L) without transfusion

⁃ Hemoglobin ≥ 90 g/L (9 g/dL) o Patients may be transfused to meet this criterion.

⁃ AST, ALT, and alkaline phosphatase (ALP) ≤2.5 × upper limit of normal (ULN), with the following exceptions:

• Patients with documented liver metastases: AST and ALT ≤ 5 × ULN

∙ Patients with documented liver or bone metastases: ALP ≤ 5 × ULN

⁃ Serum bilirubin ≤1.5 × ULN with the following exception:

‣ o Patients with known Gilbert disease: serum bilirubin ≤3 × ULN

⁃ Serum creatinine ≤1.5 × ULN}

⁃ Serum albumin ≥ 25 g/L (2.5 g/dL)

⁃ For patients not receiving therapeutic anticoagulation: INR or aPTT × 1.5 × ULN o For patients receiving therapeutic anticoagulation: stable anticoagulant regimen

• Patients with a positive HIV disease are eligible provided they are stable on anti-retroviral therapy, have a CD4 count ≥ 200/μL, and have an undetectable viral load

• No known Hepatitis infection

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:

‣ Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the final dose of pembrolizumab and E7777. Women must refrain from donating eggs during this same period.

⁃ A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.

⁃ The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.

• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:

‣ With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 5 months after the final dose of pembrolizumab + E7777 to avoid exposing the embryo. Men must refrain from donating sperm during this same period.

⁃ The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure