Clear Cell RCC
Conditions
Keywords
metastatic renal cell carcinoma, Temferon, Gene, Solid tumor, Immunotherapy
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.
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.
Interventions
GENETICTemferon
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.
BIOLOGICALPembrolizumab
Pembrolizumab 400mg IV every 6 weeks commencing at D+30
DRUGCabozantinib
40mg QD once PD occurs as assessed at D+30 or at subsequent visits
Sponsors
Genenta Science
Alira Health
Arithmos srl
Ospedale San Raffaele
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability and safety of conditioning and Temferon, over the first 90 days following administration, as determined by the incidence of adverse events | First 90 days | 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. |
| 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) | First 90 days | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Defined as the proportion of patients who achieved a complete or partial response as their best overall response |
| Disease control rate following Temferon infusion | Through study completion, an average of 1 year | — |
Countries
Italy
Outcome results
None listed