Cancer of Unknown PrimaryPhase 2Lu-FAP CUPNCT07434180
Phase II Trial of Lu-177 FAP-2286 in Patients With Carcinoma of Unknown Primary
A Phase 2 study testing 177Lu-FAP-2286 in people with Cancer of Unknown Primary, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.
Trial summary
The aim of the study is to test if a new radionuclide therapy, called 177-Lu-FAP-2286, works to treat cancer in patients with Cancer of Unknown Primary (CUP). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer of Unknown Primary
- What is being tested?
- 177Lu-FAP-2286
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteAustralia
- Study dates
- Jun 2026to Jun 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 must meet all the following criteria for trial entry:
- Patient has provided written informed consent
- Patients aged 18 years or over at Screening
- Diagnosed with CUP based on a diagnostic work-up, including, but not limited to; a detailed clinical assessment; a CT CAP; pathological review of tumour tissue; and other appropriate tests as per the Cancer Council Optimal Care Pathway guidelines.
- Progressed on 1st line platinum doublet chemotherapy +/- immunotherapy +/- antibody therapy
- 68Ga-FAPI-46 positive disease on 68Ga-FAPI-46-PET/CT defined as 68Ga-FAPI-46 uptake at PET/CT with SUVmax of ≥ 8 in at least 50% of target lesions and above surrounding background in the remaining target lesions
Show all 20Show fewer
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Appendix 1).
- Life expectancy greater than 3 months
- Adequate bone marrow, hepatic and renal function defined by the following laboratory results:
- Haemoglobin ≥ 90 g/L independent of transfusion (no red blood cell transfusion within 4 weeks before the haematology Screening assessment)
- Absolute neutrophil count ≥ 1.5 x 109/L
- Platelet count ≥ 100 x 109/L
- Creatinine clearance (CrCl) ≥ 60 mL/min calculated using the Cockcroft-Gault equation (Appendix 2)
- Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); Patients with known Gilbert's disease may have a bilirubin ≥ 3.0 x ULN
- Aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2 x ULN (or ≤ 5 x ULN in the presence of liver metastases)
- Have measurable disease per RECIST1.1 (Appendix 3)
- Sexually active Patients are willing to use medically acceptable forms of barrier contraception as outlined in Section 8.1.5.1, during treatment and for 6 months following the last dose of treatment
- Women of childbearing potential (WCBP) must have a negative serum pregnancy test result
- Willing to undergo biopsies if disease is considered accessible and biopsy is feasible
- Willing and able to comply with all trial requirements, including all treatment and required assessments and follow-up procedures, in the Investigator's judgment
Who cannot join
- Patients who meet any of the following criteria will be excluded from trial entry:
- Uncontrolled medical or psychological conditions that may prevent commencement of systemic treatment
- Symptomatic and/or untreated central nervous system metastases or leptomeningeal disease. Patients must be clinically stable for at least 4 weeks without steroid treatment
- Surgical procedure (minor surgery ≤ 5 days, or major surgery ≤ 21 days) prior to registration or active infection requiring systemic treatment Note: Placement of vascular access devices, laparoscopy and prophylactic procedures to stabilise bone lesions are not considered major surgical procedures
- Received anticancer treatment ≤ 14 days prior to registration (≤ 28 days prior in case of checkpoint inhibitor or other antibody therapies)
- Severe impaired cardiac function (left ventricular ejection fraction < 35%) or clinically significant uncontrolled cardiac disease
Show all 19Show fewer
- Severe urinary incontinence, voiding dysfunction, or unrelieved urinary obstruction
- Ongoing AEs from anticancer treatment > Grade 1 as per CTCAE v5.0, with the exception of alopecia
- Received prior radiopharmaceutical therapy or radioembolisation, or prior extensive external beam radiation therapy (EBRT) to bone marrow or any prior EBRT directly to kidney or received any EBRT within 2 weeks prior to registration
- Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo procedures outlined in this protocol with reasonable safety
- Prior cancer diagnosis with the exception of:
- Malignancy treated with curative intent and with no known active disease ≥ 3 years and of low potential risk of recurrence
- Adequately treated basal cell or squamous cell skin carcinoma or non-invasive melanoma
- Adequately treated non-muscle invasive bladder cancer (Tis, Ta and low grade T1 tumours)
- Adequately treated carcinoma in situ without evidence of disease
- Cancer patients with incidental histologic findings of prostate cancer that, in the opinion of the Investigator, is not deemed to require active therapy (e.g., incidental prostate cancer identified following cystoprostatectomy that is tumour/node/metastasis stage ≤ pT2N0)
- Greater than one prior line of systemic treatment
- Known allergy or reaction to 18F, 68Ga or 177Lu radiopharmaceuticals
- Concurrent illness, including severe infection that may jeopardise the ability of the patient to undergo the procedures outlined in the protocol with reasonable safety
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Linda Mileshkin, +61 3 8559 5000, Contact.Bact@petermac.org
Tharani Sivakumaran, +61 3 8559 5000, Contact.Bact@petermac.org
About this study
The aim of the study is to test if a new radionuclide therapy, called 177-Lu-FAP-2286, works to treat cancer in patients with Cancer of Unknown Primary (CUP).
Read the detailed description
The aim of the Lu-FAP-CUP trial is to assess preliminary efficacy signal of 177Lu-FAP-2286 in CUP patients with 68Ga-FAPI-46 positive disease.
This is a prospective, open label, single site, phase II clinical trial designed to evaluate the safety and efficacy of 177Lu-FAP-2286 monotherapy in CUP patients.
Patients who meet all eligibility criteria will be registered into the trial and receive up to 6 cycles of 177Lu-FAP-2286 monotherapy every 28 days.
- Conditions
- Cancer of Unknown Primary
- Being tested
- 177Lu-FAP-2286
- Keywords
- cancer of unknown primary, 177Lu-FAP-2286, Ga-FAPI-46, theranostic, FAP-2286, Fibroblast Activation Protein (FAP), cancer-associated fibroblasts (CAF), radiopharmaceutical, Targeted radioligand therapy (TRT), Targeted radionuclide therapy, Peptide-Targeted Radioligand Therapy (PTRT), Peptide Receptor Radionuclide Therapy (PRRT)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
177Lu-FAP-2286Drug
177Lu-FAP-2286 is a novel radioligand therapy. FAP-2286 is a small molecular ligand that binds to the fibroblast activated protein on cancer associated fibroblasts. Lutetium-177 (177Lu) is a nuclear reactor-produced radiometal with a half-life of 6.7 days.
250 mCi of 177Lu-FAP-2286 will be given once every 28 days for a maximum duration of 6 cycles of treatment.
| Study group | Role | What they receive |
|---|---|---|
| 177Lu-FAP-2286 | Experimental | In this single arm study, patients with CUP will receive up to 6 cycles of 177Lu-FAP-2286 monotherapy every 28 days. Receives: Drug: 177Lu-FAP-2286 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
ORR is defined as complete response (CR) or partial response (PR) as per RECIST1.1 at any time after commencement of treatment.
Measured: From start of treatment until end of follow-up (study completion- 2 years after the last patient has commenced treatment)
Secondary outcomes (3)
Progression Free Survival (PFS)
PFS will be measured from the date of treatment commencement to the first evidence of disease progression per RECIST1.1 oir death due to any cause
Measured: start of treatment until end of follow-up period (study completion- 2 years after the last patient has commenced treatment) or death/withdrawal of patient consent
Evaluation of Safety
Safety will be evaluated by determining the type, grade and relationship to treatment of Adverse Events (AE's), assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
Measured: From the start of treatment until the 6-week post treatment safety follow-up visit
PERCIST response
18F-FDG-PET/CT response 12 weeks after commencement of FAP-directed radioligand therapy as per PERCIST
Measured: From screening till 12 weeks after commencing treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2026
- Study startJun 2026 (estimated)
- Primary completionJun 2030 (estimated)
- Study completionJun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer of Unknown PrimaryStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peter MacCallum Cancer Centre, Australia
- Sponsor type
- University, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia, Novartis, SOFIE, University of Melbourne
- Responsible party
- Sponsor
- Investigators
- Linda Mileshkin, Principal investigator, Peter MacCallum Cancer Centre, Australia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07434180
- Sponsor's protocol ID
- 25/113
- Acronym
- Lu-FAP CUP
- Status last verified
- Aug 2025
- First submitted
- 28 Aug 2025
- Last updated
- 25 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Lu-177 FAP-2286 in Patients With Carcinoma of Unknown Primary
- ClinicalTrials.gov ID
- NCT07434180
- Acronym / sponsor ID
- Lu-FAP CUP / 25/113
- Conditions
- Cancer of Unknown Primary
- Keywords
- cancer of unknown primary, 177Lu-FAP-2286, Ga-FAPI-46, theranostic, FAP-2286, Fibroblast Activation Protein (FAP), cancer-associated fibroblasts (CAF), radiopharmaceutical
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Peter MacCallum Cancer Centre, AustraliaUniversity, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia, Novartis, SOFIE, University of Melbourne
- Study start
- Jun 2026 (estimated)
- Primary completion
- Jun 2030 (estimated)
- Study completion
- Jun 2030 (estimated)
- First posted
- 25 Feb 2026 (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.
The aim of the study is to test if a new radionuclide therapy, called 177-Lu-FAP-2286, works to treat cancer in patients with Cancer of Unknown Primary (CUP).
Detailed description
The aim of the Lu-FAP-CUP trial is to assess preliminary efficacy signal of 177Lu-FAP-2286 in CUP patients with 68Ga-FAPI-46 positive disease.
This is a prospective, open label, single site, phase II clinical trial designed to evaluate the safety and efficacy of 177Lu-FAP-2286 monotherapy in CUP patients.
Patients who meet all eligibility criteria will be registered into the trial and receive up to 6 cycles of 177Lu-FAP-2286 monotherapy every 28 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 177Lu-FAP-2286 | Experimental | Drug: 177Lu-FAP-2286In this single arm study, patients with CUP will receive up to 6 cycles of 177Lu-FAP-2286 monotherapy every 28 days. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patient has provided written informed consent
- Patients aged 18 years or over at Screening
- Diagnosed with CUP based on a diagnostic work-up, including, but not limited to; a detailed clinical assessment; a CT CAP; pathological review of tumour tissue; and other appropriate tests as per the Cancer Council Optimal Care Pathway guidelines.
- Progressed on 1st line platinum doublet chemotherapy +/- immunotherapy +/- antibody therapy
- 68Ga-FAPI-46 positive disease on 68Ga-FAPI-46-PET/CT defined as 68Ga-FAPI-46 uptake at PET/CT with SUVmax of ≥ 8 in at least 50% of target lesions and above surrounding background in the remaining target lesions
Key exclusion criteria (19 listed)
- Patients who meet any of the following criteria will be excluded from trial entry:
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 |
|---|---|---|
| 177Lu-FAP-2286177Lu-FAP-2286 is a novel radioligand therapy. FAP-2286 is a small molecular ligand that binds to the fibroblast activated protein on cancer associated fibroblasts. Lutetium-177 (177Lu) is a nuclear reactor-produced radiometal with a half-life of 6.7 days. 250 mCi of 177Lu-FAP-2286 will be given once every 28 days for a maximum duration of 6 cycles of treatment. | Drug | 177Lu-FAP-2286 |
Primary outcome
Overall Response Rate (ORR)
Time frame: From start of treatment until end of follow-up (study completion- 2 years after the last patient has commenced treatment)
ORR is defined as complete response (CR) or partial response (PR) as per RECIST1.1 at any time after commencement of treatment.
3 secondary outcomes
Progression Free Survival (PFS)
Time frame: start of treatment until end of follow-up period (study completion- 2 years after the last patient has commenced treatment) or death/withdrawal of patient consent
Evaluation of Safety
Time frame: From the start of treatment until the 6-week post treatment safety follow-up visit
PERCIST response
Time frame: From screening till 12 weeks after commencing treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2026.
- Individual participant dataSharing planned: No
Related trials for Cancer of Unknown Primary
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
Recruiting
Studying the PAGODA Algorithm for Chemotherapy Dose Changes to Prevent Unplanned Treatment Delays
Ampulla of Vater Carcinoma, Appendix Carcinoma
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Not yet recruiting
Smartphone-Based Self-Registration of Health Data in Patients With Severe Unspecific Symptoms or Cancer of Unknown Primary
Advanced Unspecific Symptom, Cancer of Unknown Primary Site
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.
Linda Mileshkin principal investigator
Peter MacCallum Cancer Centre, Australia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 177Lu-FAP-2286 in people with Cancer of Unknown Primary, run by Peter MacCallum Cancer Centre, Australia at 1 site in Australia.
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 20 inclusion and 19 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: opening soon, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Linda Mileshkin (+61 3 8559 5000, Contact.Bact@petermac.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (ORR) (time frame: From start of treatment until end of follow-up (study completion- 2 years after the last patient has commenced treatment)). 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 25 Feb 2026.