Clinical Trials /

Ph1 Study of SL-172154 Administered Intratumorally in Subjects With Squamous Cell Carcinoma of the Head and Neck or Skin

NCT04502888

Description:

This is a Phase 1 open-label, multi-center, dose-escalation study to evaluate the safety, PK, anti-tumor activity, and pharmacodynamic effects of SL-172154 administered by intratumoral injection in subjects with cutaneous squamous cell carcinoma (CSCC) or squamous cell carcinoma of the head and neck (SCCHN).

Related Conditions:
  • Cutaneous Squamous Cell Carcinoma of the Head and Neck
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Ph1 Study of SL-172154 Administered Intratumorally in Subjects With Squamous Cell Carcinoma of the Head and Neck or Skin
  • Official Title: Phase 1 Dose Escalation Study of the Agonist Redirected Checkpoint, SL-172154 (SIRPα-Fc-CD40L), Administered Intratumorally in Subjects With Cutaneous Squamous Cell Carcinoma or Squamous Cell Carcinoma of the Head and Neck

Clinical Trial IDs

  • ORG STUDY ID: SL03-OHD-102
  • NCT ID: NCT04502888

Conditions

  • Cutaneous Squamous Cell Carcinoma
  • Squamous Cell Carcinoma of Head and Neck

Interventions

DrugSynonymsArms
Drug: SL-172154SL-172154

Purpose

This is a Phase 1 open-label, multi-center, dose-escalation study to evaluate the safety, PK, anti-tumor activity, and pharmacodynamic effects of SL-172154 administered by intratumoral injection in subjects with cutaneous squamous cell carcinoma (CSCC) or squamous cell carcinoma of the head and neck (SCCHN).

Detailed Description

      This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor
      activity and pharmacodynamic effects of SL-172154 when administered as an intratumoral
      injection (ITI) and identify the dose and schedule i.e., recommended Phase 2 dose (RP2D) for
      future development. Eligible subjects must have unresectable or recurrent, locally advanced
      or metastatic squamous cell carcinoma of the skin or head and neck, that is not amenable to
      curative surgery or radiotherapy. The study design consists of four sequential
      dose-escalation cohorts and an optional 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).
    

Trial Arms

NameTypeDescriptionInterventions
SL-172154ExperimentalIntratumoral administration
  • Drug: SL-172154

Eligibility Criteria

        Inclusion Criteria:

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

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

          -  Subject must have a histologically confirmed diagnosis of an unresectable or
             recurrent, locally advanced or metastatic cutaneous squamous cell carcinoma or
             squamous cell carcinoma of the head and neck that is not amenable to curative surgery
             or radiotherapy.

          -  Subjects must have received, been intolerant to, or ineligible for standard
             therapy(ies) known to provide clinical benefit for their condition.

          -  Subject has measurable disease by RECIST v1.1 using radiologic assessment.

          -  Subject has at least 1 tumor lesion measuring between 1-6cm that is cutaneous and/or
             subcutaneous and/or nodal and is clinically accessible and safe for injection by
             direct visualization, palpation or by ultrasound guidance. PD Cohort Subjects Only:
             Must have a second lesion that is non-injected and is amenable to tumor biopsy
             collection.

          -  Subject age is 18 years and older.

          -  Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

          -  Has life expectancy of greater than 12 weeks.

          -  Has adequate organ function.

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

          -  Male subjects of reproductive potential must use acceptable contraception.

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

          -  Willing to consent to mandatory pre-treatment and on-treatment tumor biopsy(ies) of
             injected lesion (and non-injected lesion(s) for subjects enrolled in the PD cohort)

        Exclusion Criteria:

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

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

          -  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.

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

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

          -  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.

          -  History of coagulopathy resulting in uncontrolled bleeding, eg, hemophilia, von
             Willebrand's disease.

          -  Requires continuous anticoagulation therapy or antiplatelet therapy

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

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

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

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

          -  Clinically significant or uncontrolled cardiac/thromboembolic disease.

          -  Untreated central nervous system or leptomeningeal metastases.

          -  Women who are breastfeeding.

          -  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.

          -  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.

          -  Has undergone allogeneic stem cell transplantation or organ transplantation.

          -  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:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of all treatment emergent adverse events to inform the safety profile of SL-172154 when administered intratumorally
Time Frame:From Day 1 to 90 days after last injection 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 when administered by intratumoral injection (ITI)
Time Frame:Approximately 18-24 months
Safety Issue:
Description:Based on all data collected during dose-escalation and pharmacodynamic cohorts, including safety, tolerability, PK, anti-tumor activity and PD effects
Measure:Assess preliminary evidence of anti-tumor activity of SL-172154 when administered by intratumoral injection (ITI)
Time Frame:Approximately 18-24 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 when administered by intratumoral injection (ITI)
Time Frame:Approximately 18-24 months
Safety Issue:
Description:Proportion of participants with positive anti-drug antibody titer
Measure:Maximum observed concentration (Cmax) of SL-172154 when administered by intratumoral injection (ITI)
Time Frame:Approximately 18-24 months
Safety Issue:
Description:The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses
Measure:Time at which the maximum concentration is observed (Tmax) of SL-172154 when administered by intratumoral injection (ITI)
Time Frame:Approximately 18-24 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:Minimum observed concentration (Cmin) of SL-172154 when administered by intratumoral injection (ITI)
Time Frame:Approximately 18-24 months
Safety Issue:
Description:The Cmin is the minimum observed serum concentration of SL-172154 following single and multiple doses
Measure:Area under the serum concentration time curve (AUC) of SL-172154 when administered by intratumoral injection (ITI)
Time Frame:Approximately 18-24 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) of SL-172154 when administered by intratumoral injection (ITI)
Time Frame:Approximately 18-24 months
Safety Issue:
Description:Terminal elimination half-life (t1/2) of SL-172154
Measure:Clearance (CL) of SL-172154 when administered by intratumoral injection (ITI)
Time Frame:Approximately 18-24 months
Safety Issue:
Description:Clearance of Sl-172154
Measure:Volume of distribution of SL-172154 when administered by intratumoral injection (ITI)
Time Frame:Approximately 18-24 months
Safety Issue:
Description:Volume of distribtion of SL-172154

Details

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

Trial Keywords

  • intratumoral injection

Last Updated

August 4, 2020