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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Genenta Science S.p.A.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Oct 2024 → 23 Jan 2026

Decision date (initial)

2024-09-30

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Genenta Science S.p.A.

External identifiers

EU CT number

2024-512898-27-00

ClinicalTrials.gov

NCT06716853

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy, Safety, Efficacy

The first co-primary objective is to assess, over a defined period of time from the administration of the IMP, the tolerability and safety of both the conditioning regimen and Temferon.
The second co-primary objective aims to assess the biological activity of Temferon over a defined period of time following administration.

Secondary objectives 1

1. The secondary objectives will assess the long-term safety of Temferon as well as evaluating the biological activity and efficacy of Temferon for up to one (1) year after administration.

Conditions and MedDRA coding

Patients with locally advanced/metastatic renal cell carcinoma with evidence of disease progression following standard of care treatment

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Patient aged between 18 – 70 years old
2. Radiotherapy or metastasectomy of the target lesion are not scheduled within the next four (4) months following Screening
3. Disease progression following approved standard of care treatments for metastatic disease.
4. ECOG PS 0-1 at screening
5. Measurable disease at physical examination or at imaging assessment according to RECIST 1.1 criteria
6. Patient recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Participants with endocrine related AEs Grade ≤2 requiring treatment or hormone replacement are eligible
7. Women of childbearing potential must have a negative pregnancy test at screening and agree to use a highly effective method of contraception for the duration of the study.
8. Men with partners of childbearing potential must be willing to use a male condom during the trial and their partner should consider use of a highly effective method of contraception.
9. Adequate cardiac, renal, hepatic, pulmonary, and hematologic function as evidenced by: • LVEF >45% by echo and normal ECG • DLCO >50% and FEV1 and FVC>60% predicted
10. Patient able and willing to provide written informed consent and comply with study protocol and procedures
11. Histologically confirmed diagnosis of locally advanced/metastatic RCC, with or without sarcomatoid features. Previous nephrectomy or metastasectomy is also allowed.

Exclusion criteria 18

1. 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
2. Presence of clinically relevant risk factors that may increase the risk of sepsis in the first 3 months after conditioning
3. 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.
4. New CNS or rapidly growing metastases or carcinomatous meningitis
5. Previous allogenic bone marrow, renal, liver transplant
6. Prior use of immunosuppressives in the previous 4 weeks prior to enrolment (with the exception of a maximum prednisone equivalent dose of 5mg/day). Corticosteroids must be discontinued prior to entry into the study. Mineralocorticoids and corticosteroids for adrenal replacement therapy are permitted
7. Clinically relevant active viral, bacterial or fungal infection
8. Active autoimmune disease requiring disease modifying treatment, in particular psoriasis, SLE, RA, vasculitis, immune mediated peripheral neuropathies. Use of thyroxine for autoimmune hypothyroidsm is permitted
9. History of sarcoidosis
10. History of current evidence of neuropsychiatric illness including depression, schizophrenia, bipolar disorders, impaired cognitive function, dementia, or suicidal tendency
11. History of severe cardiovascular disease (e.g. NYHA Class III/IV symptoms), prior stroke, CAD requiring intervention or unresolved arrhythmias in the past 6 months, venous thromboembolism or myocardial infarction in the last 6 months, or large artery aneurysm
12. History or evidence of osteonecrosis of the jaw
13. Evidence of haematological neoplasm
14. Positive HIV – 1, HIV- 2, (serology or RNA) and/or hepatitis B (HbsAg) and/or HBV (DNA) and/or HCV RNA and/or Treponema Pallidum or Mycoplasma
15. Active alcohol or substance abuse within 6 months of the study
16. Current pregnancy or lactation
17. Expected to undergo a surgical intervention during the first 3 months of the study
18. Evidence of myelodysplasia or abnormal karyotype on bone marrow biopsy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. To assess tolerability and safety of conditioning and Temferon over a defined period of time following Temferon administration, as evaluated by: - routine clinical and laboratory surveillance; - assessment of autoimmune manifestations; - incidence of adverse events
2. To assess the biological activity of Temferon in the tumor of patients with metastatic RCC at a defined period of time following Temferon administration.

Secondary endpoints 13

1. 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
2. Incidence, severity and duration of adverse events of special interest as indicated on the study protocol
3. Proportion of patients achieving hematological recovery by Day +30
4. Identification of the presence of transduced myeloid cells in bone marrow
5. Identification of the presence of transduced myeloid cells in peripheral blood
6. Evaluate persistent transduced myeloid cells in peripheral blood
7. Change in functional status (Eastern Cooperative Oncology Group)
8. Overall response rate per RECIST version 1.1, at Baseline and at anytime after Temferon infusion, defined as the proportion of patients who achieved a complete or partial response as their best overall response
9. Median progression-free survival following Temferon infusion
10. Median overall survival following Temferon infusion
11. Disease control rate following Temferon infusion
12. Time to progression following Temferon infusion
13. Primary and / or secondary tumor biopsy and biomarker analyses

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Genenta Science S.p.A.

Sponsor organisation

Genenta Science S.p.A.

Address

Via Olgettina 58

City

Milan

Postcode

20132

Country

Italy

Scientific contact point

Organisation

Genenta Science S.p.A.

Contact name

Genenta Science

Public contact point

Organisation

Genenta Science S.p.A.

Contact name

Genenta Science

Third parties 6

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications