Phase 1 Trial of the LSD1 Inhibitor SP-2577 (Seclidemstat) in Patients With Advanced Solid Tumors

NCT03895684 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: SALA-003-AC19
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 2

Brief Summary

Phase 1, open-label, non-randomized dose finding study of SP-2577 in patients with advanced solid tumors.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of SP-2577

  Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0

  From screening through at least 30 days after end of treatment, up to approximately 24 months

Secondary Outcomes (12)

• Determine the maximum tolerated dose of SP-2577

  DLTs within the first cycle of therapy (up to 28 days)

• Characterization of pharmacokinetics of SP-2577 (area under the concentration time profile)

  At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.

• Characterization of pharmacokinetics of SP-2577 (time to maximum plasma concentration)

  At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.

• Characterization of pharmacokinetics of SP-2577 (maximum plasma concentration)

  At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.

• Characterization of pharmacokinetics of SP-2577 (half-life)

  At protocol defined time points on cycle 1 (each cycle is 28 days), day 1 and 2 and cycle 2, day 1 and 2.

Study Arms (1)

Sp-2577

EXPERIMENTAL

Twice-daily administration of oral SP-2577

Drug: SP-2577 Seclidemstat

Interventions

SP-2577 Seclidemstat DRUG

Dose escalation and dose expansion of SP-2577.

Also known as: LSD1 Inhibitor

Sp-2577

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 12 years and weight ≥ 40 kg.
• Diagnosis of advanced or recurrent, histologically or cytologically confirmed, solid malignancy that is either metastatic or unresectable. At time of enrollment, subjects must have progressed on, be intolerant of, refuse, or ineligible for, all available standard of care therapies.
• Subjects must demonstrate measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, with the exception of castration-resistant prostate cancer (CRPC) who should have progression based on the PCWG 3.0 criteria
• Karnofsky ≥70% for over ≥16 years old and Lansky ≥70% for under 16 years old, equivalent to Eastern Cooperative Oncology Group (ECOG) performance status grade 0 or 1
• Willingness to provide tumor biopsies of assessible lesions on and off treatment (Dose expansion cohort only). Optional for patients \<18 years of age.
• Able to swallow and retain orally administered medication.
• Patients must have normal organ and marrow function
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Subjects with Ewing Sarcoma. See NCT03600649, Protocol Number: SALA-002-EW16.
• Subjects with primary central nervous system tumors
• Patients who have not recovered to grade 1 or baseline from adverse events related to prior therapy excluding lymphopenia, alopecia, peripheral neuropathy and ototoxicity, which are excluded if ≥ CTCAE grade 3 (Version 5.0).
• Patients who are receiving any other investigational agents.
• Prior therapy with LSD1 targeted agents including monoamine oxidases for cancer therapy.
• Prior systemic anti-cancer treatment (chemotherapy, biologic therapy \[ie. small molecular inhibitors, monoclonal antibodies\]) within 21 days prior to Cycle 1 Day 1.
• Prior therapy with immunotherapy such as a checkpoint inhibitor, cellular therapy or vaccine therapy within 28 days prior to Cycle 1 Day 1. Patients must have recovered from any immune-related adverse events to grade 1 or baseline and require ≤ 10 mg of prednisone equivalents daily. Patients with immune-related hypothyroidism and/or hypoadrenalism may enroll while on thyroid or hydrocortisone replacement therapy, respectively.
• Prior small port palliative radiotherapy within 14 days or 42 days from definitive local control radiation (any dose greater than 50Gy).
• Anti-androgen therapies for prostate cancer, such as bicalutamide, within 4 weeks prior to enrollment. Second-line hormone therapies such as enzalutamide, abiraterone, or orteronel within 2 weeks prior to enrolment. Subjects with prostate cancer should remain on luteinizing hormone releasing hormone (LHRH) agonists or antagonists. Subjects with prostate cancer may also remain on low-dose prednisone or prednisolone up to 10 mg/day
• Prior therapy with long acting myeloid growth factor within 14 days or 7 days from a short acting myeloid growth factor.
• Participation in a prior investigational study within 30 days prior to Cycle 1 Day 1.
• Patients with progressive or symptomatic brain metastases. Patients with brain metastases may be included in this trial as long as the brain metastases have received definitive treatment and are stable (i.e., no evidence of progression). The brain metastases must be stable for a minimum of 6 weeks.
• Patients must have discontinued anti-seizure medications and steroids, except for physiologic steroid dosing (≤10 mg/day of prednisone equivalents).
• Patients currently receiving any of the following substances and cannot be discontinued 14 days prior to Cycle 1 Day 1: Moderate or strong inhibitors or inducers of major CYP isoenzymes, including grapefruit, grapefruit hybrids, pomelos, star-fruit, and Seville oranges; Moderate or strong inhibitors or inducers of major drug transporters; Substrates of CYP3A4/5 with a narrow therapeutic index
• Uncontrolled concurrent illness including, but not limited to: ongoing or active infection; transfusion dependent thrombocytopenia or anemia; psychiatric illness/social situations that would limit compliance with study requirements

Sponsors & Collaborators

• Salarius Pharmaceuticals, LLC: lead

Study Sites (2)

HonorHealth

Scottsdale, Arizona, 85258, United States

Location

Sarcoma Oncology Research Center

Santa Monica, California, 90403, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This single arm study will utilize an accelerated dose escalation, followed by a conventional 3+3 dose escalation phase to achieve maximum tolerated dose (MTD).

Study Record Dates

• First Submitted: February 14, 2019
• First Posted: March 29, 2019
• Study Start: June 25, 2019
• Primary Completion: April 13, 2021
• Study Completion: April 13, 2021
• Last Updated: October 18, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)