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

• ClinicalTrials.gov Identifier: NCT04611139
• Recruitment Status: Withdrawn
• First Posted: November 2, 2020
• Last Update Posted: March 2, 2022
• Sponsor: HonorHealth Research Institute
• Collaborators: Merck Sharp & Dohme LLC; Salarius Pharmaceuticals, LLC
• Information provided by (Responsible Party): HonorHealth Research Institute

Study Description

Brief Summary:

Open-label study of SF-2577 plus pembrolizumab in advanced, recurrent small cell ovarian cancer as well as select additional ovarian and endometrial cancers within the SWI/SNF pathway.

Condition or disease	Intervention/treatment	Phase
SCCOHT; Ovarian Clear Cell Tumor; Ovarian Endometrioid Adenocarcinoma; Endometrial Cancer	Drug: SP-2577; Drug: Pembrolizumab	Phase 1

Detailed Description:

This study is an open-label, non-randomized dose escalation and expansion study of the LSD inhibitor SP-2577 in combination with the anti PD- 1 antibody pembrolizumab in patients with advanced, recurrent small cell ovarian cancer of the hypercalcemic type (SCCOHT) as well as select additional ovarian and endometrial cancers with mutations in the genes within the SWI/SNF pathway (Ovarian Clear Cell Cancers (OCCC), Endometrioid Ovarian Cancers (EOC) and Endometrioid Endometrial Cancers (EEC).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Pilot Feasibility and Efficacy Trial of a Novel Reversible LSD1 Inhibitor SP-2577 (Seclidemstat) Plus Pembrolizumab in Select SWI/SNF-mutant Gynecologic Cancers
• Estimated Study Start Date: December 31, 2021
• Estimated Primary Completion Date: December 31, 2023
• Estimated Study Completion Date: June 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: SP-2577 Plus Pembrolizumab	Drug: SP-2577; Daily oral doses; Drug: Pembrolizumab; 200mg Q3W by IV infusion

Outcome Measures

Primary Outcome Measures :

1. Incident of AEs [ Time Frame: First dose to 90 days after last dose ]
   Incidence of Adverse Events (AEs) as measured by NCI CTCAE version 5.0
2. Incident of DLTs [ Time Frame: First dose to 90 days after last dose ]
   Incidence of dose-limiting toxicities (DLTs) during the dose escalation phase
3. Overall Response Rate [ Time Frame: Study enrollment until participant discontinuation, occurrence of PD or death (approximately 6 months to 3 years) ]
   Percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR), as determined by Investigator according to Response Evaluation in Solid Tumors (RECIST) v 1.1
4. Disease Control Rate [ Time Frame: Study enrollment until PD or loss of clinical benefit (approximately 6 months to 3 years) ]
   Percentage of participants with Disease Control (complete response, partial response, or stable disease) as determined by RECIST v1.1
5. Duration of Response [ Time Frame: Date of first occurrence of objective response to first documentation of PD (approximately 6 months to 3 years) ]
   Duration of Response as determined by the Investigator according to RECIST v1.1
6. Duration of Stable Disease [ Time Frame: Date of first occurrence of stable disease to first documentation of PD (approximately 6 months to 3 years) ]
   Duration of Stable Disease as determined by the investigator according to RECIST v 1.1
7. Progression Free Survival [ Time Frame: Start of treatment to first occurrence of PD or death (approximately 6 months to 3 years) ]
   Progression Free Survival (PFS) as determined by the Investigator according to RECIST v1.1
8. Overall Survival [ Time Frame: Start of treatment to death (approximately 2 to 3 years) ]
   Overall Survival (OS) as determined by the Investigator according to RECIST v1.1

Secondary Outcome Measures :

1. Plasma Concentration of SP-2577 [ Time Frame: 2 months ]
   Plasma concentration of seclidemstat (SP-2577)
2. ctDNA in blood and other body fluids [ Time Frame: 6 months to 2 years ]
   Proportion of circulating tumor DNA ( ctDNA) in peripheral blood and other body fluids e.g. ascitic fluid
3. Target Inhibition in Tumor Biopsies [ Time Frame: 6 months to 2 years ]
   Percentage of target inhibition by seclidemstat and pembrolizumab in tumor tissue biopsy specimens

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Type of cancer being evaluated (ovarian and endometrial)
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

HonorHealth Research Institute

Scottsdale, Arizona, United States, 85258

Sponsors and Collaborators

HonorHealth Research Institute

Merck Sharp & Dohme LLC

Salarius Pharmaceuticals, LLC

More Information

• Responsible Party: HonorHealth Research Institute
• ClinicalTrials.gov Identifier: NCT04611139
• Other Study ID Numbers: HRI-SP-2577-001
• First Posted: November 2, 2020
• Last Update Posted: March 2, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Endometrial Neoplasms; Carcinoma, Endometrioid; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Ovarian Neoplasms; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine System Diseases; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents