Phase II Trial of Lu-177 FAP-2286 in Patients With Carcinoma of Unknown Primary

NCT07434180 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 25/113
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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).

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; Targeted radioligand therapy (TRT); Targeted radionuclide therapy; Peptide-Targeted Radioligand Therapy (PTRT); Peptide Receptor Radionuclide Therapy (PRRT)

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  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

  From the start of treatment until the 6-week post treatment safety follow-up visit

• PERCIST response

  From screening till 12 weeks after commencing treatment

Study Arms (1)

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.

Drug: 177Lu-FAP-2286

Interventions

177Lu-FAP-2286 DRUG

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.

177Lu-FAP-2286

Eligibility Criteria

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

You may qualify if:

• 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
• Ga-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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• SOFIE: collaborator
• University of Melbourne: collaborator
• Peter MacCallum Cancer Centre, Australia: lead
• National Health and Medical Research Council, Australia: collaborator
• Novartis: collaborator

Study Sites (1)

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Study Officials

• Linda Mileshkin

  Peter MacCallum Cancer Centre, Australia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Linda Mileshkin

CONTACT

+61 3 8559 5000; Contact.Bact@petermac.org

Tharani Sivakumaran

CONTACT

+61 3 8559 5000; Contact.Bact@petermac.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2025
• First Posted: February 25, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: February 25, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)