ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12626001201369

Ethics application status

Approved

Date submitted

26/08/2026

Date registered

28/09/2026

Date last updated

28/09/2026

Date data sharing statement initially provided

28/09/2026

Type of registration

Prospectively registered

Titles & IDs

Public title

Lutetium-177 (177Lu-ACT319) for fibroblast activation protein (FAP)-expressing pancreatic ductal adenocarcinoma, biliary tract carcinoma and other FAP-expressing solid tumours

Scientific title

Phase 1/2 study on safety, tolerability and pharmacokinetics of Lutetium-177 (177Lu-ACT319) in patients with FAP-expressing pancreatic ductal adenocarcinoma, biliary tract carcinoma and other FAP-expressing solid tumours

Additional trial identifiers [1]

Nil known

Universal Trial Number (UTN)

Trial acronym

ACT319-101

Related trial records

Health condition

Health condition(s) studied:

FAP-expressing pancreatic ductal adenocarcinoma

biliary tract carcinoma

Other FAP-expressing solid tumours.

Condition category

Condition code

Cancer

Pancreatic

Cancer

Sarcoma (also see 'Bone') - soft tissue

Cancer

Biliary tree (gall bladder and bile duct)

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

177Lu-ACT319 administered intravenously by the nuclear medicine physician.
Part 1A: repeated IV administration across Dose Levels 1 to 4 in dose escalation. The starting dose in part 1A is (DL1) 2.2GBq, DL2 is 4.4GBq, DL3 is 7.4GBq and DL4 is 10.0 GBq. Each cycle duration is 6 weeks (+ 3 week extension window). Administration occurs on Day 1 of each 6-week cycle, 1 dose per cycle.
Part2A is a randomised dose-optimisation cohort. Eligible patients with SPECT-positive PDAC will be randomised / assigned to one of two ¹77Lu ACT319 dose levels: the recommended dose for expansion (RDE) identified from Part 1A or one dose level below the RDE (RDE-1). The randomised dose groups will be compared to evaluate safety, tolerability, radiation dosimetry and preliminary anti-tumour activity, with the objective of identifying the dose regimen with the most favourable overall benefit-risk profile for further clinical development (recommended phase 2 dose, RP2D). Treatment is administered once every 6 weeks (+ 3 week extension window) for up to 4 cycles (with up to 2 additional cycles). Dose selection is based on Part 1A results and SRC recommendations
Part 2B: repeated IV administration at the recommended Phase 2 dose. Dose level and treatment schedule will be selected based on imaging, dosimetry, safety and preliminary efficacy data in consultation with the Safety Review Committee.
Part 1B: low-dose single IV administration for imaging and dosimetry. Imaging/dosimetry substudy in selected FAP-expressing tumour types (sarcoma, CRC, NSCLC, HNSCC and TNBC). Patients receive a single low-dose IV administration of 500-1000 MBq ¹77Lu-ACT319 followed by SPECT/CT imaging and blood/urine based dosimetry at 2 hours, 24 hours, Day 4 and Day 8
Patients will undergo a SPECT scan to identify the presence of FAP avid disease. This dose is 370MBq. Should patients have sufficient FAP avid disease, and meet all other inclusion criteria; they will be eligible for part 1A. The starting dose in part 1A is (DL1) 2.2GBq, DL2 is 4.4GBq, DL3 is 7.4GBq and DL4 is 10.0 GBq. This forms the dose escalation phase. The RP2D for the expansion phase is TBC.
Patients will have 4 cycles, scheduled 6 weeks apart; with the option of 2 additional cycles (also 6 weeks apart) should the clinician feel the patient is continuing to derive benefit.
177Lu-ACT319 is provided as a clear, colourless solution for IV injection, at a concentration of 500MBq/mL.

Intervention code [1]

Treatment: Drugs

Description of the comparator or control

No separate comparator treatment identified. All stated arms are experimental and use 177Lu-ACT319 at different dose levels. For Part2A the comparison is between two doses of the same drug and patient assignment will be conducted on a 1:1 ratio.

Control group

Dose comparison

Outcomes

Primary outcome [1]

Part 1A dose escalation: safety and tolerability of 177Lu-ACT319; estimate the maximum tolerated dose and/or define the recommended dose for expansion. This will be assessed as a composite outcome.

Timepoint [1]

Therapy part 1A: Bloods, urine and safety assessments taken ahead of each 177Lu-ACT319 dose. Safety assessments will be performed at screening; Cycle 1 Days 1, 2, 4, 8, 15, 29 and 42; In subsequent cycles: on Days 1, 15, 29 and 42 and at End of Treatment. During safety follow-up, on visits at Months 3, 6, 12, 18 and 24 from first dose. DLTs will be specifically assessed during the first 42 days following the first administration of ¹77Lu-ACT319 starting on Day 1 of Cycle1.

Primary outcome [2]

Part 2A/2B dose expansion: preliminary antitumour activity by objective response rate;

Timepoint [2]

Will be performed every 6 weeks from Cycle1Day1 (±1week) from Cycle 1 Day 1 through Week 48 and every 12 weeks (±1 week) thereafter until documented disease progression, initiation of subsequent anticancer therapy, withdrawal from the study, loss to follow-up, or end of study, whichever occurs first

Primary outcome [3]

Part 1B: tumour uptake/tumour-to-background ratio on SPECT imaging in FAP-expressing tumour types

Timepoint [3]

At 2hr, 24hr, day 4 and day 8 post injection

Secondary outcome [1]

Part 1A: pharmacokinetics of 177Lu-ACT319 in Cycle 1;

Timepoint [1]

PK blood 5 min, 15 min, 30 min, 1hr, 2 hr, day 2, day 3-5, day 8 post injection. PK samples may be collected on any day within the protocol-specified window, but are not collected daily across the entire window.

Secondary outcome [2]

Part 1B: optimal imaging procedure, including timing and acquisition time; pharmacokinetics, biodistribution, dosimetry and tumour retention. This will be assessed as a composite outcome.

Timepoint [2]

Urine PK collected at 1 hr, 2 hr, day 2, day 3-5, day 8 post injection. PK samples may be collected on any day 3, 4 or 5 i.e within the protocol-specified window (one sample).

Secondary outcome [3]

Part 2A/2B: preliminary antitumour activity by progression-free survival,

Timepoint [3]

SPECT scans done at 2 hr, on day 2, at one timepoint between day 3-5 and on day 8 post injection.

Secondary outcome [4]

Part 2A/2B dose expansion: identify an optimised dose regimen / recommended Phase 2 dose

Timepoint [4]

Secondary outcome [5]

Part 1B: Safety and Tolerability

Timepoint [5]

During the 4-week screening period, Day 1, at imaging/dosimetry visits, and at the End of Treatment visit (Day8 ±2 days)

Secondary outcome [6]

Part 1A: Biodistribution of 177Lu-ACT319 in Cycle 1

Timepoint [6]

Day 1, 4 & 8 after 177Lu-ACT319 administration

Secondary outcome [7]

Part 2A/2B: safety and tolerability

Timepoint [7]

Continuously throughout study participation from first dose administration until End of Study. Scheduled safety assessments occur at Screening; Cycle 1 Days 1, 2, 4, 8, 15, 29 and 42; Days 1, 15, 29 and 42 of subsequent cycles (Cycles 2-4 and optional Cycles 5-6); End of Treatment (EOT); and Safety Follow-up visits at approximately 3 months, 6 months, 12 months, 18 months and 24 months from Cycle 1 Day 1.

Secondary outcome [8]

Part 2A/2B Overall survival

Timepoint [8]

Survival status is collected continuously throughout the study. Formal survival follow-up is performed approximately every 3 months after disease progression, initiation of subsequent anticancer therapy, or completion of treatment follow-up, continuing until End of Study or approximately 24 months from Cycle 1 Day 1, whichever occurs first

Secondary outcome [9]

Part 2A/2B disease control rate

Timepoint [9]

Tumour assessments are performed every 6 weeks (±1 week) from treatment initiation through Week 48, and every 12 weeks (±1 week) thereafter up to the EOS. DCR is specifically evaluated at approximately Month 3, Month 6 and Month 12.

Secondary outcome [10]

Part 1A Exploratory outcome: Progression-Free Survival (PFS)

Timepoint [10]

From C1D1 until progression/death

Secondary outcome [11]

Part 1A Exploratory outcome: metabolic stability of 177Lu-ACT319

Timepoint [11]

Collected in Cycle 1 at: pre-dose, end of injection, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 24 hours (±2 hours), Day 4 (4 ±1 days), and Day 8 (8 ±2 days) following administration

Secondary outcome [12]

Part 2A Exploratory outcome: Quality of life

Timepoint [12]

Screening/Baseline; Day 1 of each treatment cycle; End of Treatment (EOT); and follow-up assessments according to the protocol QoL schedule

Eligibility

Key inclusion criteria

Male and female patients aged 18 years or older at informed consent; locally advanced and/or metastatic cancer within the protocol-defined tumour populations, with no further valid treatment options; at least one measurable lesion per RECIST v1.1 by investigator assessment; SPECT positive; adequate organ and bone marrow function within 7 days before treatment; ECOG performance status 0-2; anticipated life expectancy of at least 6 months; patients with known CNS metastases may be eligible if clinically stable.
Population:
Part 1A: Patients with histologically or cytologically confirmed advanced, unresectable and/or metastatic pancreatic ductal adenocarcinoma (PDAC) or biliary tract cancer (BTC) who do not have valid treatment options. Patients must have FAP-positive disease confirmed by PET/SPECT imaging
Inclusion criteria:
- Age greater than or equal to 18 years.
- Histologically or cytologically confirmed advanced, unresectable and/or metastatic PDAC or BTC.
- At least one measurable lesion per RECIST v1.1.
- FAP-positive SPECT defined as tumour uptake greater than or equal to 2× liver uptake in at least one lesion.
- ECOG performance status 0-2
- Life expectancy greater than or equal to 6 months.
- Radiographic or clinical progression following prior therapy, or intolerance to prior therapy.
- Adequate haematologic, hepatic, renal and coagulation function
Population:
Part1B: Patients with advanced solid tumours known to express FAP, including: Sarcoma, Colorectal cancer, Tripe-negative breast cancer, head and neck squamous cell carcinoma and non-small cell lung cancer.
Inclusion criteria:
- Age greater than or equal to 18 years.
- Histologically or cytologically confirmed locally advanced and/or metastatic cancer within the prespecified tumour types.
- At least one measurable lesion per RECIST v1.1.
- ECOG performance status 0-2.
- Life expectancy greater than or equal to 6 months.
- Adequate haematologic, hepatic and renal function.
- No requirement for FAP positivity before enrolment; tumour uptake is evaluated as part of the imaging/dosimetry substudy
Population:
Part 2A: Patients with FAP-positive pancreatic ductal adenocarcinoma (PDAC) confirmed by SPECT/CT imaging.
Inclusion criteria:
- Age greater than or equal to 18 years.
- Histologically or cytologically confirmed advanced, unresectable and/or metastatic PDAC
- At least one measurable lesion per RECIST v1.1.
- FAP-positive SPECT defined as tumour uptake greater than or equal to 2× liver uptake
- ECOG performance status 0-2.
- Life expectancy greater than or equal to 6 months
- Adequate organ function.
Population:
Part 2B: Patients with FAP-positive additional tumour indication(s) selected based on emerging data from Part 1A and/or Part 1B. The final indication(s) will be determined following Safety Review Committee (SRC) review and protocol amendment.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Healthy volunteers

Key exclusion criteria

Known hypersensitivity to 177Lu-ACT319 or its excipients; uncontrolled intercurrent illness, including active infection, uncontrolled diabetes mellitus, symptomatic congestive heart failure or unstable angina; unresolved clinically significant toxicity from prior systemic cancer therapy, surgery or radiotherapy above Grade 1; active clinically significant cardiac disease; major surgery within 4 weeks before enrolment; pregnancy or breastfeeding; inability or unwillingness to comply with study requirements; known systemic fibrotic condition; concurrent systemic antineoplastic therapy and/or other investigational agents within 5 half-lives or 2 weeks, whichever is longer, before first 177Lu-ACT319 injection; radiopharmaceutical treatment within 6 weeks of IMP or 10 half-lives, whichever is longer.

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

Other design features

Part 1A: single arm dose escalation
Part 1B: single arm low dose imaging/dosimetry substudy
Part 2A: two-arm randomised dose comparison of two recommended dose-for-expansion levels
Part 2B: single arm dose expansion

Phase

Phase 1 / Phase 2

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

3/10/2026

Actual

Date of last participant enrolment

Anticipated

30/11/2028

Actual

Date of last data collection

Anticipated

31/10/2029

Actual

Sample size

Target

182

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,WA,VIC

Recruitment hospital [1]

Melbourne Theranostic Innovation Centre - North Melbourne

Recruitment hospital [2]

Peter MacCallum Cancer Centre - Melbourne

Recruitment hospital [3]

GenesisCare - St Leonards - St Leonards

Recruitment hospital [4]

ICON Cancer Centre Theranostics - Hollywood - Nedlands

Recruitment hospital [5]

GenesisCare - Murdoch - Murdoch

Recruitment hospital [6]

Greenslopes Private Hospital - Greenslopes

Recruitment postcode(s) [1]

3051 - North Melbourne

Recruitment postcode(s) [2]

3000 - Melbourne

Recruitment postcode(s) [3]

2065 - St Leonards

Recruitment postcode(s) [4]

6009 - Nedlands

Recruitment postcode(s) [5]

6150 - Murdoch

Recruitment postcode(s) [6]

4120 - Greenslopes

Recruitment outside Australia

Country [1]

Canada

State/province [1]

Country [2]

United States of America

State/province [2]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Actithera, Inc.

Address [1]

Country [1]

United States of America

Primary sponsor type

Commercial sector/Industry

Name

Actithera, Inc.

Address

Country

United States of America

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Human Research Ethics Committee A

Ethics committee address [1]

https://bellberry.com.au/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

30/06/2026

Approval date [1]

10/08/2026

Ethics approval number [1]

2026-06-1008

Summary

Brief summary

This Phase 1/2 study is evaluating safety, tolerability, pharmacokinetics and preliminary antitumour activity of different doses of Lutetium-177 in people with fibroblast activation protein (FAP)-expressing pancreatic ductal adenocarcinoma, biliary tract carcinoma and other FAP-expressing solid tumours. 
Who is it for?
You may be eligible to join this study if you are aged 18 years or above, have been diagnosed with locally advanced and/or metastatic cancer expressing FAP, including pancreatic ductal adenocarcinoma, biliary tract carcinoma and other solid tumours. 

Study details
There are 4 parts to this study. Participants will be allocated to different parts based on their tumour type and timing of allocation.
Part 1A will assess 4 different doses of Lutetium-177 administered intravenously on Day 1 of each cycle for at least 4 cycles. Safety, tolerability and recommended dose for Part 2 will be assessed in Part 1A using vital signs, laboratory values, electrocardiogram and adverse event monitoring from the time of administration until the end of each cycle. Pharmacokinetics will also be assessed for Part 1A using serum samples at specific time intervals.
Part 1B will administer a single low-dose Lutetium-177 administered intravenously on Day 1 of cycle 1. Imaging and dosimetry will be assessed using Dosimetry SPECT scan at specific times within the first 8 days of treatment. 
Part 2A will administer two recommended dose-for-expansion levels, based on dosages determined from Part 1A, for 4 cycles (6 weeks each) plus 2 optional additional cycles. Safety, tolerability and preliminary antitumour activity will be assessed using vital signs laboratory values, electrocardiogram, adverse event monitoring from the time of
administration until the end of each cycle. Quality of life will also be assessed using a questionnaire.
Part 2B will administer one recommended Phase 2 dose, based on dosages determined from Part 2A, for 4 cycles (plus additional 2 optional cycles). 
Safety, tolerability and preliminary antitumour activity using vital signs, laboratory
values, electrocardiogram, adverse event monitoring and RECIST v1.1 from the time of administration until the end of each cycle.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Giuseppe Cardaci

Address

GenesisCare Murdoch, 100 Murdoch Drive, Murdoch 6150, WA, Australia,

Country

Australia

Phone

+61 893661500

Fax

[email protected]

Contact person for public queries

Name

Jessica Preston

Address

Actithera, Inc. 1 Broadway, 14th Floor, Cambridge, MA 02142 USA

Country

Australia

Phone

+61 424 558 723

Fax

[email protected]

Contact person for scientific queries

Name

Jessica Preston

Address

Actithera, Inc. 1 Broadway, 14th Floor, Cambridge, MA 02142 USA

Country

Australia

Phone

+61 424 558 723

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

No
No IPD sharing reason/comment: The information collected about participants for this study is confidential and will be aggregated for a group analysis.

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