PBMC-based Leukocyte Immunotherapy

NCT06172894 | Completed Phase 1 DMC

• 1 other identifier: APN401-104
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Advanced Solid Tumor

Keywords

ATMP (Advanced Therapy Medicinal Product); PBMCs (Peripheral Blood Mononuclear Cells); Cbl-b (Casitas B Lineage Lymphoma B); advanced solid tumor; siRNA (small interfering ribonucleic acid); cell therapy; immune checkpoint

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment Emergent Adverse Events (TEAEs) and/or Serious Adverse Events (SAEs)

  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)

  Up to 30 days post last dose

• Occurence of Dose Limiting Toxicities (DLTs)

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

  Observed from Day 1 of APN401 infusion until the end of Cycle 1 (Day 21)

• Determination of Recommended Phase 2 Dose (RP2D) of APN401

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

  Through completion of DLT period of last evaluable patient, an average of 8 months

Secondary Outcomes (7)

• Overall Response Rate (ORR)

  Up to 12 months

• Disease Control Rate (DCR)

  Up to 12 months

• Overall Survival (OS)

  Time from enrollment to death

• Overall Survival (OS) at 3, 6 and 12 months

  At 3, 6 and 12 months post start of treatment phase

• Progression Free Survival (PFS)

  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

Study Arms (1)

APN401

EXPERIMENTAL

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

Drug: APN401

Interventions

APN401 DRUG

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

Eligibility Criteria

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

You may qualify if:

• Patients of 18 years or older (all genders)
• 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
• Progressed on or refractory to at least two prior lines of systemic therapy
• At least one measurable lesion according to RECIST 1.1
• An Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
• Life expectancy of at least 3 months
• Adequate organ and bone marrow function, in the absence of growth factors, defined by specific laboratory parameters.
• Negative serology for human immunodeficiency virus, syphilis, hepatitis B and hepatitis C
• 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
• Toxicities from previous anti-cancer therapies or surgical procedures to grade ≤1 that have not resolved (except alopecia)
• Previous exposure to a checkpoint inhibitor is allowed (except exposure of Cbl-b inhibition)
• 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
• 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
• Patient is not participating in any other interventional clinical study within the past 30 days

You may not qualify if:

• Active untreated brain metastases
• 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
• Active, known, or suspected autoimmune disease except type I diabetes, vitiligo and thyroid disorders (thyroxine or insulin replacement therapy is allowed)
• Patients at high medical risk because of non-malignant systemic disease, active or unstable cardiac or cerebro-vascular disease, or active uncontrolled infection
• 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
• Any vaccination prior and/or after 7 days while on APN401 treatment

Sponsors & Collaborators

• invIOs GmbH: lead

Study Sites (4)

Salzburg Cancer Research Institute (SCRI), Center for Clinical Cancer and Immunology Trials (CCCIT)

Salzburg, Salzburg, 5020, Austria

Location

Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin V, Hämatologie und internistische Onkologie

Innsbruck, Tyrol, 6020, Austria

Location

Ordensklinikum Linz, Barmherzige Schwestern, Abteilung für Hals-, Nasen-, Ohrenheilkunde

Linz, Upper Austria, 4010, Austria

Location

Medizinische Universität Wien, Universitätsklinik für Transfusionsmedizin und Zelltherapie

Vienna, Vienna, 1090, Austria

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2023
• First Posted: December 15, 2023
• Study Start: August 22, 2023
• Primary Completion: October 1, 2024
• Study Completion: October 1, 2024
• Last Updated: February 12, 2025

Record last verified: 2025-02

Locations

AU (4)