Clinical Trials /

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

NCT04611139

Description:

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.

Related Conditions:
  • Endometrial Endometrioid Adenocarcinoma
  • Ovarian Clear Cell Adenocarcinoma
  • Ovarian Endometrioid Adenocarcinoma
  • Ovarian Small Cell Carcinoma, Hypercalcemic Type
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Pilot Trial of SP-2577 Plus Pembrolizumab in Select Gynecologic Cancers
  • 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

Clinical Trial IDs

  • ORG STUDY ID: HRI-SP-2577-001
  • NCT ID: NCT04611139

Conditions

  • SCCOHT
  • Ovarian Clear Cell Tumor
  • Ovarian Endometrioid Adenocarcinoma
  • Endometrial Cancer

Interventions

DrugSynonymsArms
SP-2577SP-2577 Plus Pembrolizumab
PembrolizumabSP-2577 Plus Pembrolizumab

Purpose

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.

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).
    

Trial Arms

NameTypeDescriptionInterventions
SP-2577 Plus PembrolizumabExperimental
  • SP-2577
  • Pembrolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incident of AEs
Time Frame:First dose to 90 days after last dose
Safety Issue:
Description:Incidence of Adverse Events (AEs) as measured by NCI CTCAE version 5.0

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:HonorHealth Research Institute

Last Updated

October 30, 2020