Pilot Trial of SP-2577 Plus Pembrolizumab in Select Gynecologic Cancers

Inclusion Criteria:

* Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of small cell carcinoma of the ovary of hypercalcemic type (SCCOHT), ovarian clear cell carcinoma (OCCC), endometrioid ovarian carcinoma (EOC) or endometrioid endometrial carcinoma (EEC) with confirmed mutations in one of the SWI/SNF genes (SMARCA4, ARID1A) will be enrolled in this study.
* Patients must have received at least one prior regimen in the recurrent or advanced setting and must not be a candidate for other potentially curative treatment options.
* Not pregnant, breastfeeding and agrees to use contraceptive methods if child-bearing
* Provides written informed consent
* Have measurable disease based on RECIST 1.1. 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 a newly obtained core or excisional biopsy of a tumor lesion not irradiated.
* ECOG of 0 to 1
* Adequate organ function

Exclusion Criteria:

* A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.
* Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent is allowed as long as patient did not have a serious (≥ Grade 3) immune related AE requiring treatment discontinuation or treatment with systemic steroids.
* Has received prior therapy with LSD1 targeted agents including monoamine oxidases for cancer therapy.
* Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 half-lives whichever is shorter prior to the first dose of study treatment.
* Has received prior radiotherapy within 2 weeks of start of study treatment.
* Has received a live vaccine within 30 days prior to the first dose of study drug.
* 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.
* 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.
* Has known active CNS metastases and/or carcinomatous meningitis.
* 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).
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
* Has an active infection requiring systemic therapy.
* Has a known history of HIV, Hepatitis B, or known active Hepatitis C
* Has a known history of active TB
* Has clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
* Is currently receiving any of the following substances and cannot be discontinued 14 days, or 5 half-lives for CYP inhibitors (whichever is shorter) prior to Cycle 1 Day 1
* Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject 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 within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.