A Clinical Gene Therapy Study With Hematopoietic Stem Cells for the Treatment, With Single Dose of Temferon, of Patients Suffering From Metastatic Renal Cell Carcinoma (TEM-GU)

An Open-label Phase 1/2 Study to Evaluate the Safety, Biological Response and Efficacy of a Single Dose of Temferon (Autologous CD34+-Enriched Hematopoietic Stem and Progenitors Cells Genetically Modified With Human Interferon-α2) in Patients With Metastatic Renal Cell Carcinoma

This is an open label, single-centre phase 1/2 study involving a single dose of Temferon, an investigational Advanced Therapy Medicinal Product (ATMP), to treat patients with metastatic clear cell renal cell carcinoma (RCC) with evidence of disease progression following at least two lines of standard of care (SoC) treatments.

Study Overview

• Status: Terminated
• Conditions: Clear Cell RCC
• Intervention / Treatment: Genetic: Temferon; Biological: Pembrolizumab; Drug: Cabozantinib

Detailed Description

During Part A (Phase 1) of the study, Temferon will be administered to up to 12 patients, who are going to be split into two cohorts according to immune checkpoint inhibitor -ICI- therapy received in the six months prior to entry into the study, with a histologically confirmed diagnosis of metastatic RCC and evidence of disease progression following at least two lines of SoC treatments.

At D+30 after Temferon, patients will start to receive pembrolizumab providing they have not received ICI in the 6 months prior to entry into the study. Patients allocated to pembrolizumab will receive pembrolizumab 400mg IV every 6 weeks commencing at D+30.

In the event that a patient has received ICI in the 6 months prior to study entry, they will be allocated to the cabozantinib arm. Patients allocated to cabozantinib, will initiate treatment with 40mg QD once PD occurs as assessed at D+30 or at subsequent visits.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Italy
  • Italy
    • Milan, Italy, Italy, 20132
      • Ospedale San Raffaele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient aged between 18 - 70 years old
• Women of childbearing potential must have a negative pregnancy test at screening and agree to use two distinct acceptable methods of contraception (which may include partner contraception) for the duration of the study
• Men with partners of childbearing potential must be willing to use acceptable barrier contraceptive method during the trial or have undergone a vasectomy at least 6 months prior to study entry and confirmed by semen analysis
• Adequate cardiac, renal, hepatic, pulmonary, and hematologic function
• Patient able and willing to provide written informed consent and comply with study protocol and procedures
• Histologically confirmed diagnosis of unresectable, locally advanced/metastatic RCC with clear cell component, with or without sarcomatoid features
• Presence of a disease burden sufficiently large to permit biopsy
• Disease progression following approved standard of care treatments for metastatic disease
• ECOG PS 0-1
• Measurable disease at physical examination or at imaging assessment according to RECIST 1.1 criteria

Exclusion Criteria:

• Use of investigational agents or procedures in the 4 weeks prior to study enrolment (6 weeks for long-acting agents) or receipt of an experimental gene therapy product in the past 2 years
• History of current evidence of neuropsychiatric illness
• History of severe cardiovascular disease
• Evidence of haematological neoplasm
• Active alcohol or substance abuse within 6 months of the study
• Current pregnancy or lactation
• Expected to undergo a surgical intervention during the first 3 months of the study
• Known bleeding diathesis or history of abnormal/severe bleeding or any other known coagulation abnormalities that would contraindication a tissue biopsy, active treatment with anticoagulants.
• New CNS or rapidly growing metastases or carcinomatous meningitis
• Presence of hepatic metastases
• Previous allogenic bone marrow, renal, liver transplant
• Prior use of immunosuppressives in the previous 4 weeks prior to enrolment
• Clinically relevant active viral, bacterial or fungal infection
• Active autoimmune disease requiring disease modifying treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab cohort; At D+30 after Temferon, patients will start to receive pembrolizumab providing they have not received ICI in the 6 months prior to entry into the study. Patients allocated to pembrolizumab will receive pembrolizumab 400mg IV every 6 weeks commencing at D+30.	Genetic: Temferon; Autologous CD34+-enriched hematopoietic progenitor cells exposed in vitro to specific lentiviral vector encoding for the human interferon-alpha 2 gene. Its expression is tightly controlled by the human TIE2 enhancer/promoter sequence and by a post-transcriptional regulation layer represented by target miRNA sequences. This enables suppression of interferon-alpha2 expression in HSPCs, thereby further increasing the specificity of the delivery strategy for their Tie2 expressing myeloid cell progeny.; Biological: Pembrolizumab; Pembrolizumab 400mg IV every 6 weeks commencing at D+30
Experimental: Cabozantinib cohort; At D+30 after Temferon, in the event that a patient has received ICI in the 6 months prior to study entry and in case PD occurs (as assessed at D+30 or at subsequent visits), they will be receiving cabozantinib. Patients allocated to cabozantinib cohort will initiate treatment with 40mg QD	Genetic: Temferon; Autologous CD34+-enriched hematopoietic progenitor cells exposed in vitro to specific lentiviral vector encoding for the human interferon-alpha 2 gene. Its expression is tightly controlled by the human TIE2 enhancer/promoter sequence and by a post-transcriptional regulation layer represented by target miRNA sequences. This enables suppression of interferon-alpha2 expression in HSPCs, thereby further increasing the specificity of the delivery strategy for their Tie2 expressing myeloid cell progeny.; Drug: Cabozantinib; 40mg QD once PD occurs as assessed at D+30 or at subsequent visits

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability and safety of conditioning and Temferon, over the first 90 days following administration, as determined by the incidence of adverse events	To assess tolerability and safety of conditioning and Temferon over the first 90 days following Temferon administration, as evaluated by the incidence of >=CTCAE Grade 2 adverse events.	First 90 days
Biological activity of Temferon, over the first 90 days following administration, as determined by the presence of Temferon-derived progeny in the tumor (IFN gene signature)	To assess the biological activity of Temferon in the tumor of patients with metastatic renal cell carcinoma, over the first 90 days following Temferon administration, as determined by the change in IFN (interferon) gene signature in the tumor	First 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long term tolerability and safety of Temferon as determined by the incidence of adverse events up to 1 year following Temferon administration according to CTCAE v5.0 criteria		1 year following Temferon administration
Incidence, severity and duration of adverse events of special interest as indicated on the study protocol		Through study completion, an average of 1 year
Proportion of patients achieving hematological recovery by Day +30		Day 30
Overall response rate per RECIST version 1.1	Defined as the proportion of patients who achieved a complete or partial response as their best overall response	RECIST criteria used at Screening, Baseline, Day +72, Day +120, Day +180, Day +210, Day +270, Day +360 or at any time disease progression or a secondary malignancy is suspected
Disease control rate following Temferon infusion		Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Genenta Science
• Collaborators: Ospedale San Raffaele; Alira Health; Arithmos srl

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2024
• Primary Completion (Actual): January 23, 2026
• Study Completion (Actual): January 23, 2026

Study Registration Dates

• First Submitted: November 15, 2024
• First Submitted That Met QC Criteria: November 29, 2024
• First Posted (Actual): December 4, 2024

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 5, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; Solid tumor; Temferon; metastatic renal cell carcinoma; Gene
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab; cabozantinib
• Other Study ID Numbers: TEM-GU; 2024-512898-27-00 (Ctis)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No