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

NCT06716853 | Terminated Phase 1 DMC

• 2 other identifiers: TEM-GU2024-512898-27-00
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Clear Cell RCC

Keywords

metastatic renal cell carcinoma; Temferon; Gene; Solid tumor; Immunotherapy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

  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

Study Arms (2)

Pembrolizumab cohort

EXPERIMENTAL

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; Biological: Pembrolizumab

Cabozantinib cohort

EXPERIMENTAL

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; Drug: Cabozantinib

Interventions

Temferon GENETIC

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.

Cabozantinib cohort; Pembrolizumab cohort

Pembrolizumab BIOLOGICAL

Pembrolizumab 400mg IV every 6 weeks commencing at D+30

Pembrolizumab cohort

Cabozantinib DRUG

40mg QD once PD occurs as assessed at D+30 or at subsequent visits

Cabozantinib cohort

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Genenta Science: lead
• Alira Health: collaborator
• Arithmos srl: collaborator
• Ospedale San Raffaele: collaborator

Study Sites (1)

Ospedale San Raffaele

Milan, Italy, 20132, Italy

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

pembrolizumab; cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open label, single-centre phase 1/2 therapeutic-exploratory prospective study where Temferon will be administered to up to 12 patients split into two cohorts according to immune checkpoint inhibitor -ICI- therapy received in the six months prior to entry into the study.

Study Record Dates

• First Submitted: November 15, 2024
• First Posted: December 4, 2024
• Study Start: October 22, 2024
• Primary Completion: January 23, 2026
• Study Completion: January 23, 2026
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

IT (1)