Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04611139
Recruitment Status : Not yet recruiting
First Posted : November 2, 2020
Last Update Posted : December 2, 2020
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Salarius Pharmaceuticals, LLC
Information provided by (Responsible Party):
HonorHealth Research Institute

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 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 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : June 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SP-2577 Plus Pembrolizumab Drug: SP-2577
Daily oral doses

Drug: Pembrolizumab
200mg Q3W by IV infusion




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04611139


Contacts
Layout table for location contacts
Contact: Jasgit Sachdev, MD 480-323-1350 jsachdev@honorhealth.com

Locations
Layout table for location information
United States, Arizona
HonorHealth Research Institute
Scottsdale, Arizona, United States, 85258
Contact: Jasgit Sachdev, MD    480-323-1350    jsachdev@honorhealth.com   
Contact: Joyce Schaffer    480-323-1791    joschaffer@honorhealth.com   
Sponsors and Collaborators
HonorHealth Research Institute
Merck Sharp & Dohme Corp.
Salarius Pharmaceuticals, LLC
Layout table for additonal information
Responsible Party: HonorHealth Research Institute
ClinicalTrials.gov Identifier: NCT04611139    
Other Study ID Numbers: HRI-SP-2577-001
First Posted: November 2, 2020    Key Record Dates
Last Update Posted: December 2, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for 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