Clinical Trials /

Phase 1 Study of SL-172154 (SIRPα-Fc-CD40L) in Subjects With Ovarian Cancer

NCT04406623

Description:

This is a Phase 1 first in human, open label, multi-center, dose escalation study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-172154 in subjects with ovarian cancer.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Phase 1 Study of SL-172154 (SIRPα-Fc-CD40L) in Subjects With Ovarian Cancer
  • Official Title: Phase 1 Dose Escalation Study of the Agonist Redirected Checkpoint, SL-172154 (SIRPα-Fc-CD40L) Administered Intravenously in Subjects With Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: SL03-OHD-101
  • NCT ID: NCT04406623

Conditions

  • Ovarian Cancer
  • Fallopian Tube Cancer
  • Primary Peritoneal Carcinoma

Interventions

DrugSynonymsArms
SL-172154SL-172154

Purpose

This is a Phase 1 first in human, open label, multi-center, dose escalation study to evaluate the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-172154 in subjects with ovarian cancer.

Detailed Description

      This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor and
      pharmacodynamic effects of SL-172154 and identify the dose and schedule i.e., recommended
      Phase 2 dose for future development (RP2D). Subjects eligible for enrollment are required to
      have platinum-ineligible ovarian, fallopian tube, and primary peritoneal cancers. The study
      design consists of dose escalation cohorts, an optional pharmacodynamic cohort, and an
      optional dose expansion cohort. In the dose escalation phase of the study, subjects will be
      enrolled into sequential dose levels. The study may also enroll a pharmacodynamic cohort to
      obtain additional pharmacodynamic data at one or more dose levels that have completed
      evaluation for safety without exceeding the maximum tolerated dose (MTD). Subjects enrolled
      in the pharmacodynamic cohort will not inform dose escalation decisions. A dose expansion
      cohort may be opened to further characterize safety, tolerability, PK, anti-tumor activity,
      and pharmacodynamic data to inform the selection of a RP2D.
    

Trial Arms

NameTypeDescriptionInterventions
SL-172154ExperimentalIntravenous administration
  • SL-172154

Eligibility Criteria

        Inclusion Criteria:

        Participants are eligible to be included in the study only if all the following criteria
        apply:

          1. Subject has voluntarily agreed to participate by giving written informed consent in
             accordance with ICH/GCP guidelines and applicable local regulations.

          2. Subject must have a histologically confirmed diagnosis of an unresectable, locally
             advanced or metastatic ovarian cancer, or primary peritoneal cancer or fallopian tube
             cancer.

          3. Subjects must be refractory or intolerant to existing therapy(ies) known to provide
             clinical benefit for their condition. Subject must have received platinum-based
             therapies, and should not be eligible for further platinum therapy, or should be
             intolerant to such therapy. Subjects with HRD positive disease may participate if they
             have received prior polyadenosine diphosphate ribose polymerase (PARP) inhibitor
             therapy given alone or with bevacizumab.

          4. Subjects should not be primary platinum refractory as defined by progressing during or
             within 1 month of upfront platinum therapy.

          5. Has measurable disease by RECIST v1.1 using radiologic assessment.

          6. Subject age is 18 years and older.

          7. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

          8. Has life expectancy of greater than 12 weeks.

          9. Has adequate organ function.

         10. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
             test within 72 hours of D1 of IP.

         11. Recovery from prior anti-cancer treatments including surgery, radiotherapy,
             chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1.

         12. Willing to consent to mandatory pre-treatment and on-treatment tumor biopsy(ies),
             unless there is excessive risk as determined by the investigator.

        Exclusion Criteria:

        Participants are excluded from the study if any of the following criteria apply:

          1. Prior treatment with an anti-CD47 or anti-SIRPα targeting agent or a CD40 agonist.

          2. Any anti-cancer therapy within the washout period prior to first dose (D1) of
             SL-172154.

          3. Concurrent chemotherapy, immunotherapy, biologic or hormonal/hormonal suppression
             therapy for cancer treatment is prohibited. Concurrent use of hormones for non-cancer
             related conditions is acceptable.

          4. Use of corticosteroids or other immunosuppressive medication, current or within 14
             days of D1 of SL-172154 treatment.

          5. Receipt of live attenuated vaccine within 28 days of D1 of IP.

          6. Active or documented history of autoimmune disease. Exceptions include controlled Type
             I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism.

          7. Hypersensitivity to the active drug substance or to any of the excipients for the
             agent to be administered or subjects with known hypersensitivity to Chinese hamster
             ovary cell products.

          8. Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis,
             radiation-induced, etc.).

          9. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of
             infection within 5 days of D1 of IP).

         10. Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious
             gastrointestinal disease associated with diarrhea within 6 months of D1 of IP.

         11. Clinically significant or uncontrolled cardiac/thromboembolic disease.

         12. Untreated central nervous system or leptomeningeal metastases.

         13. Women who are breast feeding.

         14. Psychiatric illness/social circumstances that would limit compliance with study
             requirements and substantially increase the risk of AEs or compromised ability to
             provide written informed consent.

         15. Another malignancy that requires active therapy and that in the opinion of the
             investigator and Sponsor would interfere with monitoring of radiologic assessments of
             response to IP.

         16. Has undergone allogeneic stem cell transplantation or organ transplantation.

         17. Known history or positive test for human immunodeficiency virus, or positive test for
             hepatitis B.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety profile of SL-172154
Time Frame:From Day 1 to 90 days after Last Dose of SL-172154
Safety Issue:
Description:Incidence of all treatment emergent adverse events

Secondary Outcome Measures

Measure:Establish the recommended Phase 2 dose (RP2D) for SL-172154
Time Frame:Approximately 24 months
Safety Issue:
Description:Establish the RP2D for SL-172154
Measure:Assess preliminary evidence of anti-tumor activity of SL-172154
Time Frame:Approximately 24 months
Safety Issue:
Description:Disease assessment per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
Measure:Immunogenicity to SL-172154
Time Frame:Approximately 24 months
Safety Issue:
Description:Number and proportion of participants with positive anti-drug antibody titer
Measure:Maximum serum concentration (Cmax) of SL-172154
Time Frame:Approximately 24 months
Safety Issue:
Description:The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses
Measure:Minimum serum concentration (Cmin) of SL-172154
Time Frame:Approximately 24 months
Safety Issue:
Description:The Cmin is the minimum observed serum concentration of SL-172154 following single and multiple doses
Measure:Time at which maximum concentration of SL-172154 is observed (Tmax)
Time Frame:Approximately 24 months
Safety Issue:
Description:The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses
Measure:Area under the serum concentration-time curve (AUC)
Time Frame:Approximately 24 months
Safety Issue:
Description:The AUC is the area under the serum concentration time curve following single and multiple doses of SL-172154
Measure:Terminal elimination half-life (t1/2)
Time Frame:Approximately 24 months
Safety Issue:
Description:Terminal elimination half-life (t1/2) of SL-172154
Measure:Clearance (CL)
Time Frame:Approximately 24 months
Safety Issue:
Description:Clearance of Sl-172154
Measure:Volume of distribution
Time Frame:Approximately 24 months
Safety Issue:
Description:Volume of distribution of SL-172154

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Shattuck Labs, Inc.

Last Updated

May 22, 2020