A Study of 177Lu-FAP-2286 in Advanced Solid Tumors (LuMIERE)

Study Overview
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Brief Summary
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Phase 1 of this study will evaluate the safety and tolerability of 177Lu-FAP-2286 and determine the recommended Phase 2 dose (RP2D) in patients with advanced solid tumors. Phase 2 of this study is designed to evaluate objective response rate (ORR) in tumor-specific cohorts of patients with a FAP-expressing solid tumor.

Official Title
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LuMIERE: A Phase 1/2, Multicenter, Open-label, Non-randomized Study to Investigate Safety and Tolerability, Pharmacokinetics, Dosimetry, and Preliminary Activity of 177Lu-FAP-2286 in Patients With an Advanced Solid Tumor

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: 68Ga-FAP-2286
* Drug: 177Lu-FAP-2286
* Drug: 177Lu-FAP-2286


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be ≥ 18 years of age at the time the ICF is signed. Consent to submission of archival tumor tissue, if available. Adequate bone marrow, hepatic, and renal function. ECOG performance status of 0 or 1. Life expectancy of at least 6 months. Measurable disease per RECIST v1.1. Phase 1 only: • Patients must have an advanced/metastatic solid tumor that is refractory to or has progressed following prior treatment and has no satisfactory alternative treatment options. Phase 2 only: • Patient enrolled in Phase 2 will have one of several specific FAP-expressing tumor types with advanced or recurrent or metastatic disease following prior therapy. Exclusion Criteria: Active second malignancy that may interfere with the safety or efficacy assessments of this study Symptomatic and/or untreated central nervous system (CNS) metastases or leptomeningeal disease or with primary tumor of CNS origin. Patients must be clinically stable for at least 4 weeks without steroid treatment Received anticancer treatment ≤ 14 days prior to receiving study treatment (≤ 28 days prior in case of checkpoint inhibitor or other antibody therapies) Received prior radiopharmaceutical therapy or radioembolization, 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 administration of study treatment Ongoing adverse effects from anticancer treatment > Grade 1, with the exception of alopecia Known incompatibility with contrast media for CT or PET scans. Infection requiring systemic antibiotics within 2 weeks prior to administration of study treatment Impaired cardiac function or clinically significant cardiac disease Severe urinary incontinence, voiding dysfunction, or urinary obstruction Minor surgery ≤ 5 days, or major surgery ≤ 21 days, prior to administration of study treatment. Any other condition that may increase the risk associated with study participation or interfere with its interpretation. Refusal to use highly effective method of contraception, as applicable Pregnant or breastfeeding Any other condition that may increase the risk associated with study participation or interfere with its interpretation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Dose Escalation<br>Up to 30 patients with solid tumors. | Drug: 68Ga-FAP-2286<br>* 68Ga-FAP-2286 IV administered as imaging agent for PET scan.<br>Drug: 177Lu-FAP-2286<br>* Patients with positive uptake of 68Ga-FAP-2286 will receive a fixed dose of 177Lu-FAP-2286 IV administered every 6 weeks for a maximum of 6 doses. Doses range between 3.7 and 9.25 GBq (100-250 mCi).<br>|
| Experimental: Phase 1: Electrocardiogram (ECG) and Pharmacokinetic (PK) Cohort<br>Up to 30 patients with solid tumors. | Drug: 68Ga-FAP-2286<br>* 68Ga-FAP-2286 IV administered as imaging agent for PET scan.<br>Drug: 177Lu-FAP-2286<br>* Patients with positive uptake of 68Ga FAP 2286 will receive a fixed dose of 177Lu FAP 2286 IV administered at the RP2D and schedule determined in Phase 1 dose escalation.<br>|
| Experimental: Phase 2: Specific Solid Tumors<br>Cohorts of up to 30 patients each with FAP-expressing advanced or solid tumors | Drug: 68Ga-FAP-2286<br>* 68Ga-FAP-2286 IV administered as imaging agent for PET scan.<br>Drug: 177Lu-FAP-2286<br>* Patients with positive uptake of 68Ga FAP 2286 will receive a fixed dose of 177Lu FAP 2286 IV administered at the RP2D and schedule determined in Phase 1 dose escalation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the recommended Phase 2 dose of 177Lu-FAP-2286 (Phase 1) | Incidence of adverse events, serious adverse events, and clinical laboratory abnormalities defined as dose-limiting toxicities (DLTs) | From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 2 years) | 
| Objective response rate (ORR) (Phase 2) | Investigator-assessed Confirmed Response (CR) or Partial Response (PR) per RECIST v1.1 | From first dose of study drug until disease progression (up to approximately 2 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiation dosimetry of 177Lu-FAP-2286 (Phase 1) | Absorbed dose (gray [Gy]) estimated in organs and tumor lesions | From first dose of study drug until disease progression or end of treatment (up to approximately 9 months) | 
| Tumor uptake using 68Ga-FAP-2286 (Phase 1) | Maximum standardized uptake value (SUVmax) in tumor lesions assessed by PET/CT scan | Taken within 2 hours after 68Ga-FAP-2286 IV administration | 
| Tumor uptake of 68Ga-FAP-2286 as compared to 2-deoxy-2-[18F]fluoro-D-glucose (FDG) (Phase 1) | Comparison of SUVmax in tumor lesions | From time of screening FDG PET/CT to 68Ga-FAP-2286 PET/CT (up to approximately 1 month) | 
| Pharmacokinetics (PK) of 177Lu-FAP-2286 (Phase 1) | Concentration at the end of infusion (Ceoi) | From first dose of study drug to end of Cycle 6 with (each cycle   6 weeks) (Total Time Frame estimated up to approximately 9 months) | 
| Pharmacokinetics (PK) of 177Lu-FAP-2286 (Phase 1) | Area under the curve (AUC) | From first dose of study drug to end of Cycle 6 with (each cycle   6 weeks) (Total Time Frame estimated up to approximately 9 months) | 
| Pharmacokinetics (PK) of 177Lu-FAP-2286 (Phase 1) | Clearance (CL) | From first dose of study drug to end of Cycle 6 with (each cycle   6 weeks) (Total Time Frame estimated up to approximately 9 months) | 
| Pharmacokinetics (PK) of 177Lu-FAP-2286 (Phase 1) | Volume of distribution (Vd) | From first dose of study drug to end of Cycle 6 with (each cycle   6 weeks) (Total Time Frame estimated up to approximately 9 months) | 
| Pharmacokinetics (PK) of 177Lu-FAP-2286 (Phase 1) | Half-life (t1/2) | From first dose of study drug to end of Cycle 6 with (each cycle   6 weeks) (Total Time Frame estimated up to approximately 9 months) | 
| Preliminary efficacy of 177Lu-FAP-2286 in advanced solid tumors (Phase 1) | Investigator-assessed objective response by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | From first dose of study drug until disease progression (up to approximately 2 years) | 
| Duration of response (DOR) (Phase 2) | DOR per RECIST v1.1, as assessed by investigator | From time of initial response until disease progression (up to approximately 2 years) | 
| Progression-free survival (PFS) (Phase 2) | Disease progression according to RECIST v1.1, as assessed by investigator, or death due to any cause | From first dose of study drug until disease progression (up to approximately 2 years) | 
| Disease control rate | Evaluate confirmed partial response (PR) or complete response (CR), or stable disease (SD) of at least 12 weeks | From first dose of study drug through at least 12 weeks after end of treatment (Total Time Frame estimated up to approximately 6 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FAP, 177Lu-FAP-2286, 68Ga-FAP-2286, theranostic, FAP-2286, fibroblast activation protein, dosimetry, CAF, cancer-associated fibroblasts, Peptide-Targeted Radioligand Therapy, PTRT, Peptide Receptor RadionuclideTherapy, PRRT, TRT, Targeted radioligand therapy, Target radionuclide therapy, Lutetium-177, Gallium-68