Abstract 476P
Background
CyPep-1 is a synthetic tumor membrane targeting 27-D-aminoacid alpha-helical peptide. Preclinical studies with CyPep-1 have demonstrated immunogenic cell death and synergism with anti-PD1 antibodies. The dose-escalation part of this study assessed safety and determined the recommended dose for further development (RP2D).
Methods
Patients with assessable and injectable non-ulcerating cutaneous or subcutaneous tumor deposits were eligible. Three predefined dose levels (DL) of CyPep-1 were studied: 0.5, 2 and 5 mg/mL. CyPep-1 was administered intratumorally (IT) every 14 days for 3 doses in volumes up to 4 mL per administration, depending on tumor size. Preferentially IT administration was pursued in a single lesion, but up to 3 lesions could be injected. PK Blood samples were collected pre-dose and 15, 30, 60 & 240 min. post-dose after the first IT administration. Cytokines, TCR clonality & blood cell immunophenotyping were assessed pre-dose and on days 15 & 36 post-dose. Pre- and post-treatment biopsies from an injected lesion were analyzed. The DLT observation period was 6 weeks. Response assessment was performed every 8 weeks.
Results
Fourteen pts were enrolled, twelve completed the DLT period: 3 DL1, 3 DL2, 6 in DL3. All pts had exhausted SoC therapy. No DLT was observed. One pt discontinued treatment after three IT administrations due to ulceration of the injected lesion. Injection site reactions were noted in 79% (11/14), mainly mild pain (related to IT administration). No grade 3 or higher treatment related AEs were observed. PK: Concentrations below limit of quantification in 5 pts (10 ng/mL). Six pts had detectable levels that peaked at 15 minutes. Highest concentration observed in 1 pt was 226 ng/mL. Tumor biopsy analysis revealed increased cell death and necrosis (range 10-80%) in 5 of 6 pts at DL3. TCR clonality: increased clonality in peripheral blood after treatment. Two patients had iRECIST SD lasting > 8 months.
Conclusions
CyPep-1 IT is well tolerated at the RP2D of 5.0 mg/mL. PK data showed minimal systemic exposure with IT injection. Histopathologic examination showed local oncolytic effect, and TCR clonal changes were consistent with systemic immune activation.
Clinical trial identification
NCT04260529.
Editorial acknowledgement
Legal entity responsible for the study
Cytovation AS.
Funding
Cytovation AS.
Disclosure
L. Prestegarden: Financial Interests, Personal, Full or part-time Employment, Stocks/Shares: Cytovation. C. Pico-Navarro: Financial Interests, Personal, Full or part-time Employment: Cytovation. All other authors have declared no conflicts of interest.