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

Squamous Cell Carcinoma of Head and Neck Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT04502888
• Other study ID #: SL03-OHD-102
• Status: Terminated
• Phase: Phase 1
• Start date: September 17, 2020
• Est. completion date: April 8, 2022

Study information

• Verified date: December 2022
• Source: Shattuck Labs, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: April 8, 2022
• Est. primary completion date: April 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-SIRPa 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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Drug: SL-172154
The investigational product (IP), SL-172154, is a novel fusion protein consisting of human SIRPa and CD40L (SIRPa -Fc-CD40L) linked via a human Fc.

Locations

Country	Name	City	State
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of California, Los Angeles	Los Angeles	California
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Shattuck Labs, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	Immunogenicity to SL-172154 when administered by intratumoral injection (ITI)	Proportion of participants with positive anti-drug antibody titer	Approximately 18-24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Clearance (CL) of SL-172154 when administered by intratumoral injection (ITI)	Clearance of Sl-172154	Approximately 18-24 months
Secondary	Volume of distribution of SL-172154 when administered by intratumoral injection (ITI)	Volume of distribtion of SL-172154	Approximately 18-24 months