Sponsor decision

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).

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).

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.