1053P - Tumor-restricted delivery of an immune-therapeutic payload by modified macrophages for the treatment of glioblastoma: The TEM-GBM STUDY (NCT03866109)

Background

The tumor microenvironment (TME) is a dynamic network including factors and host cells influencing cancer progression. TEMs (Tie2-Expressing Monocytes), a subset of tumor-associated myeloid cells transiently recruited to tumors and contributing to its progression, are an attractive target for the design of novel anticancer therapy.

Methods

TEM-GBM is an open-label, Phase 1/2a dose-escalation study evaluating safety and efficacy of Temferon in up to 27 newly diagnosed, unmethylated-MGMT GBM patients. The patients are assigned to 8 cohorts and receive a single increasing dose of Temferon. Temferon is a genetically modified, autologous hematopoietic stem cell-based therapy designed to deliver IFNα into the TME via Tie-2 expressing monocytes.

Results

As of February 2023, 4 doses of Temferon (0.5-3.0x106/kg) were tested across 18 patients assigned to 6 cohorts. Follow-up from surgery is 6–36mo (2–32mo after Temferon). To date, no DLTs have been identified. In all patients, there was fast hematological recovery from the sub-myeloablative conditioning regimens used and rapid engraftment of gene modified cells, which persisted, albeit at lower levels, up to 24 mo (longest time of analysis). Median OS is 15mo from surgery. To determine if Temferon therapy leads to a detectable adaptive immune response, T cell immunorepertoire was assessed in the tumor samples, at first and, when performed, second surgery (6 cases), and in peripheral blood cells. TCR analysis suggests a correlation between Temferon doses and T cell populations present in the TME, particularly in patients treated by higher doses of Temferon. The frequency of peripherally expanded clones found in the tumor samples increases by the second surgery, as evidence of a notable crosstalk between the peripheral and tumor repertoires of T cells.

Conclusions

The results provide initial evidence of Temferon’s potential to reprogram GBM TME and elicit T cell-mediated immune responses.

Clinical trial identification

NCT03866109.

Editorial acknowledgement

Legal entity responsible for the study

Genenta Science SpA.

Funding

Genenta Science SpA.

Disclosure

F. Ciceri: Financial Interests, Institutional, Principal Investigator: Genenta Science SpA. B. Gentner: Financial Interests, Personal, Stocks/Shares: Genenta Science SpA; Financial Interests, Personal, Financially compensated role, Advisor: Genenta Science SpA; Financial Interests, Personal, Research Funding: Genenta Science SpA. M. Eoli: Financial Interests, Institutional, Principal Investigator: Genenta Science SpA. S. Mazzoleni: Financial Interests, Personal, Full or part-time Employment: Genenta Science SpA; Financial Interests, Personal, Stocks/Shares: Genenta Science SpA. L. Naldini: Financial Interests, Personal, Stocks/Shares: Genenta Science SpA; Financial Interests, Personal, Financially compensated role, Advisor: Genenta Science SpA; Financial Interests, Personal, Research Funding: Genenta Science SpA. C. Russo: Financial Interests, Personal, Full or part-time Employment: Genenta Science SpA; Financial Interests, Personal, Stocks/Shares: Genenta Science SpA. G. Finocchiaro: Financial Interests, Institutional, Coordinating PI: Genenta Science SpA. All other authors have declared no conflicts of interest.