Advanced Solid TumorPhase 1PALINDROMNCT06172894
PBMC-based Leukocyte Immunotherapy
A Phase 1 study testing APN401 in people with Advanced Solid Tumor, run by invIOs GmbH at 4 sites in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- APN401
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 4 sitesAustria
- Study dates
- 22 Aug 2023to 1 Oct 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
4 sites in 1 country.
Austria4 sites
Medizinische Universität Innsbruck, Universitätsklinik für Innere Medizin V, Hämatologie und internistische Onkologie
Innsbruck, Tyrol, 6020
Ordensklinikum Linz, Barmherzige Schwestern, Abteilung für Hals-, Nasen-, Ohrenheilkunde
Linz, Upper Austria, 4010
Salzburg Cancer Research Institute (SCRI), Center for Clinical Cancer and Immunology Trials (CCCIT)
Salzburg, State of Salzburg, 5020
Medizinische Universität Wien, Universitätsklinik für Transfusionsmedizin und Zelltherapie
Vienna, State of Vienna, 1090
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Advanced Solid Tumor
- Being tested
- APN401
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
APN401Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: APN401 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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
Measured: Through completion of DLT period of last evaluable patient, an average of 8 months
Secondary outcomes (7)
Overall Response Rate (ORR)
Preliminary data on clinical efficacy of APN401 will be assessed according to RECIST 1.1
Measured: Up to 12 months
Disease Control Rate (DCR)
Preliminary data on clinical efficacy of APN401 will be assessed according to RECIST 1.1
Measured: Up to 12 months
Overall Survival (OS)
Preliminary data on clinical efficacy of APN401 will be assessed
Measured: Time from enrollment to death
Overall Survival (OS) at 3, 6 and 12 months
Preliminary data on clinical efficacy of APN401 will be assessed
Measured: At 3, 6 and 12 months post start of treatment phase
Progression Free Survival (PFS)
Preliminary data on clinical efficacy of APN401 will be assessed according to RECIST 1.1
Measured: 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
Progression Free Survival (PFS) Rate at 3 months
Preliminary data on clinical efficacy of APN401 will be assessed according to RECIST 1.1
Measured: At 3 months post start of treatment phase
Immune responses in circulation to monitor APN401 immune activation
Preliminary data on clinical efficacy of APN401 will be assessed using ELISA-based techniques
Measured: Prior to treatment cycles C1, C2, C3, C4 (each cycle is 21 +/- 3 days) and 21 days (+/-10 days) post last APN401 dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2023
- Study start22 Aug 2023
- Primary completion1 Oct 2024
- Study completion1 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- invIOs GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06172894
- Sponsor's protocol ID
- APN401-104
- Acronym
- PALINDROM
- Status last verified
- Feb 2025
- First submitted
- 24 Nov 2023
- Last updated
- 12 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06172894
- Acronym / sponsor ID
- PALINDROM / APN401-104
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- invIOs GmbHIndustry (pharma, biotech, devices)
- Study start
- 22 Aug 2023 (actual)
- Primary completion
- 1 Oct 2024 (actual)
- Study completion
- 1 Oct 2024 (actual)
- First posted
- 15 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| APN401 | Experimental | Drug: APN401Intravenous 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| APN401APN401 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. | Drug | APN401 |
Primary outcome
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)
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
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
7 secondary outcomes
Overall Response Rate (ORR)
Time frame: Up to 12 months
Disease Control Rate (DCR)
Time frame: Up to 12 months
Overall Survival (OS)
Time frame: Time from enrollment to death
Overall Survival (OS) at 3, 6 and 12 months
Time frame: At 3, 6 and 12 months post start of treatment phase
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
Progression Free Survival (PFS) Rate at 3 months
Time frame: At 3 months post start of treatment phase
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing APN401 in people with Advanced Solid Tumor, run by invIOs GmbH at 4 sites in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment Emergent Adverse Events (TEAEs) and/or Serious Adverse Events (SAEs) (time frame: Up to 30 days post last dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2025.