ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12626000350325

Ethics application status

Approved

Date submitted

9/12/2025

Date registered

19/03/2026

Date last updated

24/06/2026

Date data sharing statement initially provided

19/03/2026

Type of registration

Prospectively registered

Titles & IDs

Public title

Phase I/Ib, Open-label, Dose Escalation and Expansion Study to Assess the safety, Tolerability, Pharmacokinetic and Preliminary Efficacy of ACS2015, Non-viral Gene-modified CAR-T Cells in Patients with Advanced Solid Tumors Expressing EPHB4

Scientific title

Additional trial identifiers [1]

CARTiEr E312

Universal Trial Number (UTN)

Trial acronym

Related trial records

Health condition

Health condition(s) studied:

solid tumours

colorectal cancer

hepatocellular carcinoma

soft tissue sarcoma

bone sarcoma

Condition category

Condition code

Cancer

Bone

Cancer

Bowel - Back passage (rectum) or large bowel (colon)

Cancer

Liver

Cancer

Other cancer types

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

This is a multi-site Phase I/Ib open-label study to assess the safety, tolerability, PK , PD and preliminary efficacy of ACS2015 when administered to patients with colorectal cancer, hepatocellular carcinoma, or bone or soft tissue sarcoma that are EPHB4 positive.

The investigational product ACS2015 expresses a CAR molecule that specifically binds to EPHB4. The CAR molecule is comprised of an antigen recognition site, hinge region, transmembrane domain, and intracellular domain. If the investigational product recognizes cells that express EPHB4, it confers acquisition of effector functions, such as activation, proliferation, and cytotoxicity. Owing these actions, the drug is expected to be effective in killing tumor cells in EPHB4-positive tumors. ACS2015 is administered via intravenous infusion. The day of ACS2015 infusion is designated as Day 1. Patients will first undergo pre-screening (immunohistochemistry) at any time before treatment.

The study will be conducted in 2 parts: Dose Escalation (Phase I) and Dose Expansion (Phase Ib)

Patients who provide consent will undergo apheresis to harvest PBMCs, which will be used to manufacture ACS2015. After final eligibility is confirmed, patients will receive ACS2015 on Day 1. This study will have 6 periods:
1. Pre-Screening
2. Screening (may occur from 7 weeks to 6 months prior to starting study treatment)
3. Lymphodepletion (over 3 consecutive days)
4. Treatment
5. End of Study (for 1 year after the last dose of the study treatment)
6. Follow-up

This study is planned to last approximately 12 months at a minimum and with a long term follow-up of 15 years. The 15 year follow up will be a seperate study.

Dose escalation (Phase I) - up to 12 patients per tumor type (up to 36 in total).- This phase will initially commence with a standard 3+3 dose escalation design in patients with CRC, starting at Dose Level 1. A staggered dosing approach will be utilized, whereby the first patient will be monitored for the full dose-limiting toxicity (DLT) period (Day 1 to Day 28) prior to enrolling additional patients. If no DLTs are observed in the first 3 CRC patients at dose level 1, and upon approval from the Safety Review Committee (SRC). Dose Level 2 may be evaluated in CRC patients, using standard 3+3 rules. Dose Level 1 may be evaluated in patients with HCC and BSTS separately, using an accelerated 3+3 design, whereby Dose Level 1 may be evaluated in a single patient cohort before proceeding with a standard 3+3 design for Dose Level. The starting dose of ACS2015 will be Dose Level 1 following lymphodepletion. Additional dose levels may be evaluated at the discretion of the SRC, in consultation with the study Sponsor.

Staggered Dosing (Phase I, Dose Escalation Only):
First 3 patients per dose level (standard 3+3 design):
• During the Dose Escalation period, there will be one full DLT period (Day 1 to Day 28) before the initiation of lymphodepletion therapy for the subsequent patient
• The first, second, and third patients at each dose level will be enrolled in this manner to allow for adequate safety assessment. This staggered approach ensures real-time safety monitoring while maintaining efficient dose escalation or de-escalation.

Phase Ib: Dose Expansion - up to 4 participants per tumor type (up to 12 in total).
In the Dose Expansion (Phase Ib) part of the study, up to 4 additional patients will be enrolled in each cohort at the highest tumor-specific dose tested, or at the MTD identified.

A total of up to 48 patients will be required overall for both Phase I and Phase Ib.

Adherence to the intevention will be monitored continously by site staff as patients are dosed as in-patients.

Intervention code [1]

Treatment: Drugs

Intervention code [2]

Treatment: Other

Description of the comparator or control

No Control groups

Control group

Uncontrolled

Outcomes

Primary outcome [1]

(Composite outcome)To evaluate the safety and tolerability of ACS2015 when administered to adults with EPHB4 positive advanced solid tumors

Timepoint [1]

(Composite outcome) DLT - Day of ACS2015 administration on day 1 and extending to Day 28. TEAE - Any AE reported or observed on the day of or after the start of dosing with any study treatment (ACS2015) will be classified as a treatment-emergent adverse event (TEAE). In addition, any pre-existing condition that worsens in severity on the day of or after the start of dosing with any study treatment will be classified as a TEAE.

Secondary outcome [1]

(Composite outcome) To determine the highest tested or maximum tolerated dose (MTD) according to DLT, including possible side effects of ACS2015 when administered to adults with EPHB4 positive advanced solid tumors

Timepoint [1]

(Composite) Safety timepoints - Screening, once within 14 days of Day -6, Day -1, Day 1, Day 3, Day 8, Day 15, day 22, Day 29. Day 43, Day 57 and Day 85.

Secondary outcome [2]

Pharmacokinetic profile of ACS2015 when administered to adults with EPHB4 positive advanced solid tumors

Timepoint [2]

- CAR transgene copy number by quantitative polymerase chain reaction- Day 1 - Postdose, Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85, Day 183. - Peripheral blood CAR- T cell counts (quantified in PBMCs)- Day 1, Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, Day 43, Day 57, Day 85, Day 183.

Eligibility

Key inclusion criteria

1. Must have given written informed consent before any study-related activities are performed and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
2. Adult males and females, 18 to 70 years of age (inclusive) at Screening.
3. A biopsy or surgical specimen contains at least 1% tumor cells positive for EPHB4 expression, confirmed by pre-Screening IHC staining. Archival biopsy material is acceptable.
4. Have suitable venous access for blood sampling.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Manufacturing can provide the assigned dose at a minimum of CAR-positive T cells per kg of ACS2015, calculated based on the patient’s body weight at the time of cell collection.
7. Presence of a measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
8. Female volunteers:
a. Must be of nonchildbearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the Screening visit or postmenopausal (where postmenopausal is defined as no menses for at least 12 months without an alternative medical cause and a follicle-stimulating hormone [FSH] level consistent with postmenopausal status, per local laboratory guidelines),
or
b. If of childbearing potential, must:
i. Have a negative pregnancy test at the Screening visit, prior to starting lymphodepletion therapy on Day -6, and on admission to the study site on Day -1
ii. Agree not to attempt to become pregnant or donate ova from at least one month prior to Screening until at least 1 year after the last dose of study therapy, or, until CAR-T cells are no longer present by polymerase chain reaction (PCR)
iii. Agree to use adequate contraception (defined as use of a condom by the male partner combined with use of a highly effective method of contraception from one month prior to Screening until at least 1 year after the last dose of study therapy, if not exclusively in a same-sex relationship or abstinent as a committed lifestyle.
9. Male volunteers, must:
a. Agree not to donate sperm from signing the Screening consent form until at least 1 year after the last dose of study therapy, or until CAR-T cells are no longer present by PCR
b. If engaging in sexual intercourse with a female partner who could become pregnant, agree to use adequate contraception (defined as use of a condom combined with use of a highly effective method of contraception [see Section 10.3.3 for more detail]) from signing the consent form until at least 1 year after the last dose of study therapy or until CAR-T cells are no longer present by PCR
c. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, agree to use a condom from signing the consent form until at least 1 year after the last dose of study therapy or until CAR-T cells are no longer present by PCR
10. Willing and able to comply with all study assessments, including LTFU study, and adhere to the protocol schedule and restrictions
11. A life expectancy of equal to 3 months from the date of enrolment

Minimum age

18 Years

Maximum age

70 Years

Sex

Both males and females

Healthy volunteers

Key exclusion criteria

1. Patients with a history of thrombosis or thromboembolism (pulmonary embolism or deep vein thrombosis), with the exception of patients who were diagnosed was equal to 90 days prior to Screening and with no risk of recurrence.
2. Patients with serious cardiovascular disease, including patients with a history or complication of Class III congestive heart failure, unstable angina, or myocardial infarction as per New York Heart Association criteria within 6 months prior to Screening, or serious arrhythmia at Screening).
3. Patients with a history of or current interstitial lung disease/pneumonitis or (non-infectious) interstitial pneumonia/ pneumonitis requiring steroids.
4. Patients with a history of hypersensitivity or anaphylactic reactions to ACS2015 or its components (CryoStor CS10 and human serum albumin as excipients).
5. Patients who have previously received any form of gene therapy (5 years for Adeno-associated virus vectors, or 15 years for all others), with the exceptions of mRNA-type and DNA-type vaccines.
6. Patients with a history of allogeneic hematopoietic stem cell transplantation.
7. Patients with active autoimmune diseases (exceptions include Hashimoto’s thyroiditis on stable thyroid replacement therapy and type 1 diabetes myelopathy on stable insulin therapy).
8. Patients with pericardial effusion, ascites, or pleural effusion requiring therapeutic procedures (drainage, shunt, cell-free and concentrated ascites reinfusion therapy) performed within 2 weeks of Screening, OR a clinical plan for regular drainage (e.g., scheduled monthly or more frequent interventions) to control symptoms or prevent complications.
9. Patients with a history of or current cerebrovascular disorders (cerebral infarction, cerebral hemorrhage) or transient ischemic attack within 180 days prior to Screening.
10. History of anaphylaxis or other significant allergy which, in the opinion of the PI (or delegate), would interfere with the volunteer’s ability to participate in the study.
11. Patients with active dual malignancies or a history of dual malignancies within the past 2 years, with the exception of: adequately treated basal cell carcinoma, squamous cell carcinoma, carcinoma in situ of the cervix, non-invasive breast cancer, and completely excised gastric mucosal cancer. Metachronous ipsilateral or bilateral breast cancer is not considered dual malignancy if one treatment is complete and a disease-free period of 5 years has elapsed.
12. Participation in another clinical study of an investigational drug or investigational device within 30 days or 5 half-lives of the investigational drug (whichever is shorter) prior to Screening.
13. Patients who have received a live vaccine within 28 days before enrolment.
14. Patients confirmed at Screening to be positive for any of the following tests: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) antibody, human T cell lymphotropic virus antibody (HTLV 1 and 2 antibody), human immunodeficiency virus antibody (HIV 1 and 2), syphilis antibody, nucleic acid testing (NAT) for HIV, HBV, HCV. Note that HBsAb positive is not exclusionary and viral load should be assessed ( less than 500 IU/mL acceptable, or at PI discretion).
15. Patients with a current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medication within 10 days prior to ACS2015 administration.
16. Screening echocardiogram (ECHO) assessments showing an ejection fraction of 28 days prior to Day 1).
c. Nitrosoureas or mitomycin C within 6 weeks prior to Day 1.
19. Patients receiving localized palliative radiation (not inclusive of the primary tumor location) can be allowed on the study after discussion with the Sponsor.
20. Patients with brain metastases or spinal cord compression syndrome. Note: Patients who are asymptomatic, clinically stable (3 months) with no evidence of progression at time of study enrolment, and do not require CNS-directed treatment may be enrolled at PI discretion.
21. Pregnant or breastfeeding females.
22. Patients currently treated with systemic corticosteroids or systemic immunosuppressive agents, with the exception of prednisolone equivalent of 10 mg/day.
23. Patients who cannot adhere to scheduled visits, treatment plans, laboratory tests, or other study procedures are excluded.
24. Any other condition or prior therapy that in the opinion of the PI (or delegate) would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Other design features

Phase

Phase 1

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

29/09/2026

Actual

Date of last participant enrolment

Anticipated

31/12/2028

Actual

Date of last data collection

Anticipated

31/12/2029

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,SA,VIC

Recruitment hospital [1]

The Royal Adelaide Hospital - Adelaide

Recruitment hospital [2]

Peter MacCallum Cancer Centre - Melbourne

Recruitment hospital [3]

Chris O’Brien Lifehouse - Camperdown

Recruitment postcode(s) [1]

5000 - Adelaide

Recruitment postcode(s) [2]

3000 - Melbourne

Recruitment postcode(s) [3]

2050 - Camperdown

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

A-Seeds Australia Pty Ltd

Address [1]

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

A-Seeds Australia Pty Ltd

Address

Country

Australia

Secondary sponsor category [1]

Commercial sector/Industry

Name [1]

Avance Clinical Pty Ltd

Address [1]

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Peter MacCallum Cancer Centre Human Research Ethics Committee

Ethics committee address [1]

https://www.petermac.org/research/doing-research-us/ethics-governance

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

08/09/2025

Approval date [1]

06/11/2025

Ethics approval number [1]

Ethics committee name [2]

Bellberry Human Research Ethics Committee A

Ethics committee address [2]

https://bellberry.com.au/

Ethics committee country [2]

Australia

Date submitted for ethics approval [2]

23/09/2025

Approval date [2]

28/11/2025

Ethics approval number [2]

Ethics committee name [3]

Central Adelaide Local Health Network HREC

Ethics committee address [3]

https://www.rah.sa.gov.au/research/for-researchers/central-adelaide-local-health-network-human-research-ethics-committee

Ethics committee country [3]

Australia

Date submitted for ethics approval [3]

29/09/2025

Approval date [3]

Ethics approval number [3]

Summary

Brief summary

This multi-site Phase I/Ib open-label study will investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ACS2015, a non-viral gene-modified CAR-T cell therapy, in adults with advanced solid tumors expressing EPHB4.

Who is it for?
You may be eligible to join this study if you are aged 18 to 70 years and have a histologically confirmed advanced solid tumor (such as colorectal cancer, hepatocellular carcinoma, or bone/soft tissue sarcoma) where at least 1% of tumor cells are positive for EPHB4. Additional eligibility criteria include good performance status (ECOG 0–1), suitable venous access, and measurable disease.

Study details:
The study will be conducted in two parts:
• Phase I (Dose Escalation): Up to 36 participants (12 per tumor type) will receive ACS2015 at increasing dose levels using a staggered 3+3 design to determine the maximum tolerated dose (MTD).
• Phase Ib (Dose Expansion): Up to 12 additional participants (4 per tumor type) will receive ACS2015 at the highest safe dose identified.
Participants will first undergo pre-screening to confirm EPHB4 expression using tumor tissue. If eligible, they will proceed to screening and apheresis to collect peripheral blood mononuclear cells (PBMCs), which will be used to manufacture ACS2015. After lymphodepletion over 3 days, ACS2015 will be administered as a single infusion on Day

It is hoped that this research will provide a new treatment option for patients with advanced solid tumors who have limited therapeutic alternatives, by targeting EPHB4 with a novel CAR-T cell therapy designed to reduce immune exhaustion and improve durability compared to conventional approaches.

Trial website

Trial related presentations / publications

Public notes

Dosage details - dosage details have not been public provided at this stage.

Rationale- Specific dosage details are not publicly disclosed to protect proprietary and confidential information. The study will be conducted in accordance with the approved protocol which is HREC approved by all the respective HRECs at each of the sites, which contains full dosage information reviewed by regulatory authorities and ethics committees.

Information will be made publicly available following the grant of a purpose-limited patent for the therapy.

Contacts

Principal investigator

Name

Dr Stephen Luen

Address

Peter MacCallumCancer Centre Victorian Comprehensive Cancer Centre Building, 305 Grattan Street,VIC 3000

Country

Australia

Phone

+61 385595000

Fax

[email protected]

Contact person for public queries

Name

Takuji Achiwa

Address

A-Seeds Australia Pty Ltd, Level 3/62 Lygon St, Carlton VIC 3053

Country

Australia

Phone

+61370429963

Fax

[email protected]

Contact person for scientific queries

Name

Takuji Achiwa

Address

A-Seeds Australia Pty Ltd, Level 3/62 Lygon St, Carlton VIC 3053

Country

Australia

Phone

+61370429963

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

No
No IPD sharing reason/comment: Privacy and Intellectual property considerations

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically