PBMC-based Leukocyte Immunotherapy

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT06172894

Studienbeginn:
August 2023

Letztes Update:
20.02.2024

Wirkstoff:
APN401

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
invIOs GmbH

Collaborator:
-

Kontakt

Nina Worel, aoUniv.Prof.Dr.
Kontakt:
Phone: +43140400
Phone (ext.): 54990
E-Mail: nina.worel@meduniwien.ac.at» Kontaktdaten anzeigen

Studienlocations
(3 von 4)

Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin V, Hämatologie und internistische Onkologie
6020 Innsbruck
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Dominik Wolf, Univ.Prof.Dr.
Phone: 0043512
Phone (ext.): 504-24003
E-Mail: dominik.wolf@i-med.ac.at» Ansprechpartner anzeigen

Ordensklinikum Linz, Barmherzige Schwestern, Abteilung für Hals-, Nasen-, Ohrenheilkunde
4010 Linz
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Martin Burian, Univ.Prof.Dr.
Phone: 00437327677
Phone (ext.): 7340
E-Mail: martin.burian@ordensklinikum.at» Ansprechpartner anzeigen

Salzburg Cancer Research Institute (SCRI), Center for Clinical Cancer and Immunology Trials (CCCIT)
5020 Salzburg
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Richard Greil, Univ.Prof.Dr.
Phone: 004357255
Phone (ext.): 25800
E-Mail: r.greil@salk.at» Ansprechpartner anzeigen

Medizinische Universität Wien, Universitätsklinik für Transfusionsmedizin und Zelltherapie
1090 Vienna
AustriaRekrutierend» Google-Maps
Ansprechpartner:
Nina Worel, aoUniv.Prof.Dr.
Phone: 0043140400
Phone (ext.): 54990
E-Mail: nina.worel@meduniwien.ac.at» Ansprechpartner anzeigen

Alle anzeigen

Studien-Informationen

Detailed Description:

APN401 is a suspension of autologous Peripheral Blood Mononuclear Cells (PBMCs), transiently

transfected with an siRNA to reduce Cbl-b protein levels. The administration of autologous

Cbl-b silenced PBMCs to the patient will promote activation of both adaptive and innate

immune mechanisms targeting tumor cells; along these lines APN401 is assumed to demonstrate

significant improvement in cancer immune therapy. In addition, silencing of Cbl-b in the

context of cellular therapeutics has potential to reduce mortality rates for patients with

advanced cancers.

This is an open-label, single-arm trial to be conducted with up to twelve patients at four

hospitals in Austria, Europe. Two dose levels of APN401 are evaluated using a Bayesian

Optimal Interval (BOIN) study design with accelerated titration:

- Dose Level/Cohort 1: 1.5x10^7 PBMCs/kg

- Dose Level/Cohort 2: 4.5x10^7 PBMCs/kg

Dose escalation requires at least one patient to be treated and observed for at least three

weeks after the first dose. The BOIN method will be used to guide the dose level assignment

and estimate the MTD/RP2D based on cumulative information on DLTs in Cycle 1 of treatment

(i.e. 3 weeks after first dose).

Patients with advanced solid tumors first undergo screening procedures during a 28-day time

window between giving consent and starting APN401 treatment. Eligible patients are treated

with up to four APN401 infusions. During each treatment cycle, patients undergo leukapheresis

on the first day and APN401 infusion on the second day (i.e., D0/D1; D21/D22; D42/D43;

D63/D64). During the subsequent follow-up phase, patients participate a safety-follow up 3

weeks post last APN401 dose and are contacted by telephone to evaluate survival status at 6

and 12 months after start of treatment. Tumor imagings to evaluate the efficacy of APN401

treatment are scheduled during the screening phase (baseline imaging), and prior to treatment

Cycle 3 and the last Safety Follow-up.

Ein-/Ausschlusskriterien

Inclusion Criteria:

1. Patients of 18 years or older (all genders)

2. Patients with histologically or cytologically confirmed locally advanced or metastatic

solid tumors and who have failed standard treatment, have no standard treatment, or

are not suitable for standard treatment at this stage as determined by the

investigator

3. Progressed on or refractory to at least two prior lines of systemic therapy

4. At least one measurable lesion according to RECIST 1.1

5. An Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

6. Life expectancy of at least 3 months

7. Adequate organ and bone marrow function, in the absence of growth factors, defined by

specific laboratory parameters.

8. Negative serology for human immunodeficiency virus, syphilis, hepatitis B and

hepatitis C

9. No prior chemotherapy, radiation therapy (except for palliative purpose), endocrine

therapy, immunotherapy or investigational agent within 3 weeks (or five half-lives)

prior to Day 0 (6 weeks for nitrosoureas and mitomycin C) before treatment

10. Toxicities from previous anti-cancer therapies or surgical procedures to grade ≤1 that

have not resolved (except alopecia)

11. Previous exposure to a checkpoint inhibitor is allowed (except exposure of Cbl-b

inhibition)

12. Women of childbearing potential must have a negative pregnancy test, should not be

breastfeeding, and must be willing to use highly effective methods of contraception

for at least 1 month before, while participating in this study and until 1 month after

the end of the treatment

13. Patient voluntarily agrees to participate in this study and signs an Ethics Committee

approved informed consent prior to performing any of the screening visit procedures,

indicating that the patient understands the purpose and procedures required for the

study

14. Patient is not participating in any other interventional clinical study within the

past 30 days

Exclusion Criteria:

1. Active untreated brain metastases

2. Use of systemic corticosteroids (> 10 mg prednisone or equivalent) within 15 days

(except for prophylaxis for radiodiagnostic contrast reactions), or other

immunosuppressive drugs within 30 days, prior to the first dose of APN401. Replacement

therapy (e.g., physiologic corticosteroid replacement therapy for adrenal or pituitary

insufficiency) is not considered a form of systemic treatment and is allowed

3. Active, known, or suspected autoimmune disease except type I diabetes, vitiligo and

thyroid disorders (thyroxine or insulin replacement therapy is allowed)

4. Patients at high medical risk because of non-malignant systemic disease, active or

unstable cardiac or cerebro-vascular disease, or active uncontrolled infection

5. Any other severe acute or chronic medical or psychiatric condition, or laboratory

abnormality that may increase the risk associated with study participation or APN401

administration, or may interfere with the interpretation of study results and, in the

judgement of the investigator, would make the patient unsuitable for the study

6. Any vaccination prior and/or after 7 days while on APN401 treatment

Studien-Rationale

Primary outcome:

1. Incidence of Treatment Emergent Adverse Events (TEAEs) and/or Serious Adverse Events (SAEs) (Time Frame - Up to 30 days post last dose):
The safety and tolerability of APN401 will be assessed by recording the TEAEs and SAEs using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0)

2. Occurence of Dose Limiting Toxicities (DLTs) (Time Frame - Observed from Day 1 of APN401 infusion until the end of Cycle 1 (Day 21)):
The safety and tolerability of APN401 will be assessed by recording DLTs

3. Determination of Recommended Phase 2 Dose (RP2D) of APN401 (Time Frame - Through completion of DLT period of last evaluable patient, an average of 8 months):
RP2D will be determined on the BOIN recommendations (based on DLT and MTD) and the overall safety information

Secondary outcome:

1. Overall Response Rate (ORR) (Time Frame - Up to 12 months):
Preliminary data on clinical efficacy of APN401 will be assessed according to RECIST 1.1

2. Disease Control Rate (DCR) (Time Frame - Up to 12 months):
Preliminary data on clinical efficacy of APN401 will be assessed according to RECIST 1.1

3. Overall Survival (OS) (Time Frame - Time from enrollment to death):
Preliminary data on clinical efficacy of APN401 will be assessed

4. Overall Survival (OS) at 3, 6 and 12 months (Time Frame - At 3, 6 and 12 months post start of treatment phase):
Preliminary data on clinical efficacy of APN401 will be assessed

5. Progression Free Survival (PFS) (Time Frame - From date of enrollment until the date of first evidence of disease progression or date of death from any cause, whichever came first, assessed up to 12 months):
Preliminary data on clinical efficacy of APN401 will be assessed according to RECIST 1.1

6. Progression Free Survival (PFS) Rate at 3 months (Time Frame - At 3 months post start of treatment phase):
Preliminary data on clinical efficacy of APN401 will be assessed according to RECIST 1.1

7. Immune responses in circulation to monitor APN401 immune activation (Time Frame - Prior to treatment cycles C1, C2, C3, C4 (each cycle is 21 +/- 3 days) and 21 days (+/-10 days) post last APN401 dose):
Preliminary data on clinical efficacy of APN401 will be assessed using ELISA-based techniques

Geprüfte Regime

APN401:
APN401 is a suspension of viable peripheral blood mononuclear cells (PBMCs) from an individual patient that have been transfected with a small interfering ribonucleic acid (siRNA) to reduce Cbl-b expression. It is administered intravenously in 3-weekly intervals (i.e. every 21 days) for a maximum of 4 treatment cycles.

Quelle: ClinicalTrials.gov

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