Temferon Linked to Long-Term Survival in Some With Glioblastoma

Two patients treated with Temferon have lived three years post-surgery: © stock.adobe.com.

Two long-term survivors treated with Temferon have lived three years post-surgery, in the TEM-LT long-term follow-up study of patients with newly diagnosed glioblastoma, according to a news release from Genenta.

One of the patients had no disease progression or a need for second line therapies following Temferon, while the other showed initial signs of disease progression that subsequently stabilized without additional therapeutic intervention.

Both cases suggest Temferon may help control disease progression, supporting the need for further research in larger studies, according to the news release.

“For the first time, we show that hematopoietic stem cells can be engineered to durably give rise to myeloid cells that localize to the tumor and reprogram its immune environment,” Professor Luigi Naldini, co-founder of Genenta Science, said in the news release. “In glioblastoma, this strategy induced a pro-inflammatory shift in macrophages and the emergence of tumor-reactive T cells, offering a promising new avenue for immune engagement against one of the most resistant cancers.”

At the April data cutoff, patients with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) in the glioblastoma trial had a two-year survival rate of 29% and a median overall survival of 17 months. By comparison, historical data for similar patients treated with standard treatment had a two-year survival rate of around 14% and median overall survival of 13 to 15 months.

“We are encouraged by the consistent clinical signals emerging from our glioblastoma trial,” Pierluigi Paracchi, CEO of Genenta Science, said in the release. “These findings reinforce our confidence in Temferon’s differentiated mechanism and support our commitment to advancing the platform.”

Temferon reprograms the tumor microenvironment to help trigger and sustain adaptive immune responses. It is designed to deliver immune-activating payloads directly into the tumor microenvironment via bone marrow–derived myeloid cells, aiming for a durable and targeted immune response. In addition, a study highlighting its ability to enhance and prolong CAR-T activity in preclinical models of solid tumors has been accepted by Science Translational Medicine, as per the release.

Recruitment is underway for the phase 1 TEM-GU study, which aims to enroll 12 patients with genitourinary tumors. In this trial, Temferon is given at the same dose previously shown to be safe and tolerated well in the dose-ranging TEM-GBM study. The trial will evaluate Temferon in combination with immune checkpoint inhibitors or tyrosine kinase inhibitors to explore potential immunologic synergy in patients with metastatic renal cell carcinoma. Genenta expects to demonstrate the safety and tolerability of Temferon in this population by the end of the year. Additional updates will follow once more patient data are available.

TEM-GBM Trial Overview for Glioblastoma

The open-label, non-randomized phase 1/2a TEM-GBM trial enrolled patients with newly diagnosed supratentorial glioblastoma and an unmethylated MGMT gene promoter. Eligible participants had undergone full or partial tumor removal, were candidates for radiotherapy, had a Karnofsky score of at least 70, and a life expectancy of at least six months. Cardiac, liver, kidney, and lung function had to be adequate, with left ventricular ejection fraction of at least 45% and no severe pulmonary hypertension, all confirmed within 20 days of Temferon treatment.

Patients were enrolled in one of eight cohorts (three patients each) and received escalating doses of Temferon alongside one of three conditioning regimens. Doses ranged from 0.5 million to 4 million CD34-positive cells per kilogram, with cohort-specific adjustments: cohorts 1 through 4 and 6 received 0.5 to 3 million cells/kg, cohort 5 received 2 million, cohort 7 received 3 million, and cohort 8 received 4 million.

The primary goal was to assess safety and tolerability in the first 90 days. Secondary goals included clinical response, progression-free survival, overall survival, hematologic recovery within 30 days, and long-term safety.

References

1. “Genenta announces long-term follow-up observations in brain tumor (GBM) study with emerging survival signals.” News release. Genenta. July 1, 2025. Accessed July 1, 2025.
2. “The European Commission grants orphan drug designation to Temferon™ for treatment of glioma.” News release. Genenta Science. June 29, 2023. Accessed July 1, 2025.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.