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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

Conditions
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Cutaneous Squamous Cell Carcinoma, Squamous Cell Carcinoma of Head and Neck

Intervention / Treatment
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* Drug: Drug: SL-172154


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SL-172154<br>Intratumoral administration | Drug: Drug: SL-172154<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intratumoral injection