72TiP - Next-generation T-cell receptor T cell therapy (SCG142) against human papilloma virus (HPV) for patients with recurrent or metastatic HPV16/52-positive carcinomas

Background

The overall prognosis of patients with recurrent/ metastatic HPV-positive carcinomas remain poor, and effective treatment options beyond first-line therapy are limited. SCG142 is a next-generation autologous HPV-specific T cell receptor (TCR) T cell product, armored with a TGFβRII-41BB chimeric switch receptor (CSR). SCG142 exhibits a high functional avidity towards HPV E7_11-19, able to transform the immunosuppressive effect of TGF-β to co-stimulatory signal, which led to enhanced tumor killing and T cell persistence. The first-in-human (FIH) study to evaluate safety and preliminary efficacy in patients with recurrent/metastatic HPV16-positive carcinomas is actively enrolling.

Trial design

The FIH study in a multicenter, open-label, single-arm, dose escalation study for patients with HPV16-positive carcinoma who had progressed after at least 1 line of standard therapy. Patients with HLA-A*02:01 positive, measurable disease (RECIST v1.1), adequate organs function and an ECOG PS 0-1 were enrolled. SCG142 at 3 dose levels (1 × 10⁷, 5 × 10⁷ or 1 × 10⁸cells/kg), administered intravenously following three days of cyclophosphamide (500 mg/m²/day) and fludarabine (25 mg/m²/day) were evaluated. The study's primary endpoint is the safety and tolerability of SCG142. Secondary endpoints include efficacy (objective response rate, best overall response, duration of response, disease control rate, durable response rate, time to response, progression-free survival, and overall survival) and pharmacokinetics. Exploratory endpoints include biomarkers and immunogenicity. A phase I/2 study with similar study design to evaluate SCG142's safety and preliminary efficacy in patients with recurrent/metastatic HPV16/52- positive carcinomas that progressed after at least one line of systemic therapy has received FDA IND approval, and currently open for recruitment.

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

SCG Cell Therapy Pte Ltd.

Disclosure

H. Lv: Financial Interests, Institutional, Local PI: SCG Cell Therapy Pte. Ltd.; Non-Financial Interests, Personal, Principal Investigator: SCG Cell Therapy Pte. Ltd. M. Ding: Financial Interests, Personal, Full or part-time Employment: SCG Cell Therapy Pte. Ltd. X. Wang: Financial Interests, Personal, Full or part-time Employment: SCG Cell Therapy. K. Zhang: Financial Interests, Personal, Full or part-time Employment: SCG Cell Therapy; Financial Interests, Personal, Stocks/Shares: SCG Cell Therapy; Non-Financial Interests, Personal, Leadership Role: SCG Cell Therapy.