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

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

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).

Study Overview

• Status: Terminated
• Conditions: Squamous Cell Carcinoma of Head and Neck; Cutaneous Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Drug: SL-172154

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).

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California, Los Angeles
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SL-172154; Intratumoral administration	Drug: Drug: SL-172154; The investigational product (IP), SL-172154, is a novel fusion protein consisting of human SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of all treatment emergent adverse events to inform the safety profile of SL-172154 when administered intratumorally	Incidence of all treatment-emergent adverse events	From Day 1 to 90 days after last injection of SL-172154
Maximum Tolerated Dose (MTD) of SL-172154 when administered intratumorally	Defined based on the rate of dose limiting toxicities (DLTs)	From Day 1 to 90 days after last injection of SL-172154

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Establish the recommended Phase 2 dose (RP2D) for SL-172154 when administered by intratumoral injection (ITI)	Based on all data collected during dose-escalation and pharmacodynamic cohorts, including safety, tolerability, PK, anti-tumor activity and PD effects	Approximately 18-24 months
Assess preliminary evidence of anti-tumor activity of SL-172154 when administered by intratumoral injection (ITI)	Disease assessment per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)	Approximately 18-24 months
Immunogenicity to SL-172154 when administered by intratumoral injection (ITI)	Proportion of participants with positive anti-drug antibody titer	Approximately 18-24 months
Maximum observed concentration (Cmax) of SL-172154 when administered by intratumoral injection (ITI)	The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses	Approximately 18-24 months
Time at which the maximum concentration is observed (Tmax) of SL-172154 when administered by intratumoral injection (ITI)	The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses	Approximately 18-24 months
Minimum observed concentration (Cmin) of SL-172154 when administered by intratumoral injection (ITI)	The Cmin is the minimum observed serum concentration of SL-172154 following single and multiple doses	Approximately 18-24 months
Area under the serum concentration time curve (AUC) of SL-172154 when administered by intratumoral injection (ITI)	The AUC is the area under the serum concentration time curve following single and multiple doses of SL-172154	Approximately 18-24 months
Terminal elimination half-life (t1/2) of SL-172154 when administered by intratumoral injection (ITI)	Terminal elimination half-life (t1/2) of SL-172154	Approximately 18-24 months
Clearance (CL) of SL-172154 when administered by intratumoral injection (ITI)	Clearance of Sl-172154	Approximately 18-24 months
Volume of distribution of SL-172154 when administered by intratumoral injection (ITI)	Volume of distribtion of SL-172154	Approximately 18-24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in cell counts to assess pharmacodynamic biomarkers in blood prior to, on-treatment and following SL-172154 when administered by intratumoral injection (ITI)	Circulating immune cells such as: T cells, B cells, natural killer (NK) cells, and myeloid cells and circulating chemokine and cytokine levels	Approximately 18-24 months
Changes from baseline in cell counts to assess pharmacodynamic biomarkers in tumor tissue prior to, on-treatment and following SL-172154 when administered by intratumoral injection (ITI)	Presence of SL-172154 in tumor tissue, changes in T cells subsets, B cells and macrophages and assessment of SL-172154 in the tumor tissue, CD47 and CD40 expression and Programmed cell death ligand 1 (PD-L1) expression	Approximately 18-24 months
To estimate progression-free survival (PFS)	PFS: time from first dose to progression by RECIST v1.1 or death, whichever comes first	Approximately 18-24 months

Collaborators and Investigators

• Sponsor: Shattuck Labs, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2020
• Primary Completion (Actual): April 8, 2022
• Study Completion (Actual): April 8, 2022

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: August 4, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: intratumoral injection
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: SL03-OHD-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No