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Intravenous infusion of APN401 in 3-weekly (i.e. 21 days) intervals for a maximum of 4 doses at either 1.5x10\^7 PBMCs/kg (i.e., Dose Level 1) or 4.5x10\^7 PBMCs/kg (i.e., Dose Level 2), depending on assigned cohort

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.

APN401

Nina Worel, aoUniv.Prof.Dr.

Dominik Wolf, Univ.Prof.Dr.

Martin Burian, Univ.Prof.Dr.

Richard Greil, Univ.Prof.Dr.

This is an open-label, multicenter, dose-escalation Phase Ib trial of APN401, 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. Twelve evaluable participants with advanced solid tumors will be assessed. The primary objective is to evaluate the safety and tolerability of APN401 and to determine the Recommended Phase 2 Dose (RP2D) of APN401. The secondary objective is to collect preliminary data on the clinical efficacy of APN401.

Participants will receive up to four APN401 treatments via intravenous infusion at 3-weekly intervals. Participants, who have completed four treatment cycles and a safety follow-up, will be contacted by telephone to evaluate survival status at 6 and 12 months after start of treatment.

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.

PBMC-based Leukocyte Immunotherapy

An Open-label, Multi-center, Dose-escalation Phase Ib Study to Determine the Recommended Phase 2 Dose of APN401 in Patients With Advanced Solid Tumors

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)

The safety and tolerability of APN401 will be assessed by recording DLTs

RP2D will be determined on the BOIN recommendations (based on DLT and MTD) and the overall safety information

Preliminary data on clinical efficacy of APN401 will be assessed according to RECIST 1.1

Preliminary data on clinical efficacy of APN401 will be assessed

Preliminary data on clinical efficacy of APN401 will be assessed using ELISA-based techniques

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PBMC-based Leukocyte Immunotherapy	NCT06172894	Advanced Solid ...	APN401	18 Years -	invIOs GmbH
PBMC-based Leukocyte Immunotherapy	NCT06172894	Advanced Solid ...	APN401	18 Years -	invIOs GmbH

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