Temferon (Autologous CD34+ enriched HSPCs expressing interferon-alpha 2)

P1/2, N=27, Recruiting, Genenta Science | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

P1/2, N=12, Recruiting, Genenta Science

The other four patients with 2 year follow-up were treated with Gamma-Knife followed by bevacizumab (n = 1), regorafenib followed by bevacizumab (n = 1) and bevacizumab only (n = 2). These data corroborate the initial evidence on safety and tolerability of Temferon. They also suggest that Temferon has potential to counteract disease progression in patients affected by uMGMT GBM.

The comparison of the overall ISGs expression at first surgery and second surgery highlighted the activation of IFN-responsive genes at second surgery suggesting the occurrence of the local delivery within the TME of biologically active IFN-a. CONCLUSION The results provide initial evidence of Temferon’s potential to modulate the TME of GBM patients.

Autologous CD34+ HSPC are mobilized with lenograstim and plerixafor, collected by apheresis, purified and ex vivo modified with a lentiviral vector. So far, up to 3 million Temferon cells/kg have been co-administered with a fixed dose of non-manipulated CD34+ supporter cells following a sub-myeloablative conditioning regimen (Thiotepa + BCNU or Busulfan or Busulfan alone)... These data show that Temferon is safe and biologically active at the tumor site and favors anti-tumor immunity. The results provide initial evidence of Temferon's potential to modulate the TME of GBM patients and to counteract disease progression and improve the survival of uMGMT GBM patients.

P1/2, N=27, Recruiting, Genenta Science | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2023

Autologous CD34+ HSPC are mobilized with lenograstim and plerixafor, collected by apheresis, purified and ex vivo modified with a lentiviral vector that enables HSC TEMs progeny to be loaded with IFN-a. So far, up to 3 million Temferon cells/kg have been co-administered with a fixed dose of non-manipulated CD34+ supporter cells following a sub-myeloablative conditioning regimen (Thiotepa + BCNU/Busulfan)... Our interim results show that Temferon is well tolerated, with no dose limiting toxicities identified to date. The results provide initial evidence of Temferon's potential to modulate the TME of GBM patients, and anecdotal evidence for long lasting effects of Temferon in prevention of disease progression.

The results provide initial evidence of Temferon's potential to modulate the TME of GBM patients, and anecdotal evidence for long lasting effects of Temferon in prevention of disease progression.

Conclusion Our interim results show that Temferon is well tolerated, with no dose limiting toxicities identified to date. The results provide initial evidence of Temferon’s potential to modulate the TME of GBM patients.

TEM-GBM is an ongoing open-label, Phase 1/2a dose-escalating study evaluating the safety & efficacy of Temferon in up to 21 newly diagnosed patients with glioblastoma & unmethylated MGMT promoter assigned to 7 different cohorts (3 pts each) differing by Temferon dose (0.5-4.0x106/kg) and conditioning regimen (BCNU+ or Busulfan+Thiotepa). TCR sequencing of blood and tumor samples showed a post-treatment increase in the cumulative frequency of tumor-associated T cell clones identified in 1st and 2nd surgery specimens (up to 4 out of 9 subjects). These results provide initial evidence for on-target activity of Temferon in GBM, to be consolidated with longer follow up in the higher dose cohorts.

TME characterization by scRNA and TCR sequencing is ongoing. Interim results show that Temferon is well tolerated, with no dose limiting toxicities identified to date and provide initial evidence of potential immune system activation within the TME.