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

• ClinicalTrials.gov Identifier: NCT04939610
• Recruitment Status: Recruiting
• First Posted: June 25, 2021
• Last Update Posted: August 29, 2022
• Sponsor: Clovis Oncology, Inc.
• Information provided by (Responsible Party): Clovis Oncology, Inc.

Study Description

Brief Summary:

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 patients with specific solid tumors.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Drug: 68Ga-FAP-2286; Drug: 177Lu-FAP-2286	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 170 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: July 30, 2021
• Estimated Primary Completion Date: July 1, 2024
• Estimated Study Completion Date: June 1, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1: Dose Escalation; Up to 30 patients with solid tumors.	Drug: 68Ga-FAP-2286; 68Ga-FAP-2286 IV administered as imaging agent for PET scan.; Drug: 177Lu-FAP-2286; 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).
Experimental: Phase 1: RP2D Expansion Cohort; Up to 20 patients with solid tumors.	Drug: 68Ga-FAP-2286; 68Ga-FAP-2286 IV administered as imaging agent for PET scan.; Drug: 177Lu-FAP-2286; 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.
Experimental: Phase 2: Specific Solid Tumors; Cohorts of up to 40 patients each with Advanced or Solid Tumors	Drug: 68Ga-FAP-2286; 68Ga-FAP-2286 IV administered as imaging agent for PET scan.; Drug: 177Lu-FAP-2286; 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Radiation dosimetry of 177Lu-FAP-2286 (Phase 1) [ Time Frame: From first dose of study drug until disease progression or end of treatment (up to approximately 9 months) ]
   Absorbed dose (gray [Gy]) estimated in organs and tumor lesions
2. Tumor uptake using 68Ga-FAP-2286 (Phase 1) [ Time Frame: Taken within 2 hours after 68Ga-FAP-2286 IV administration ]
   Maximum standardized uptake value (SUVmax) in tumor lesions assessed by PET/CT scan
3. Tumor uptake of 68Ga-FAP-2286 as compared to 2-deoxy-2-[18F]fluoro-D-glucose (FDG) (Phase 1) [ Time Frame: From time of screening FDG PET/CT to 68Ga-FAP-2286 PET/CT (up to approximately 1 month) ]
   Comparison of SUVmax in tumor lesions
4. Pharmacokinetics (PK) of 177Lu-FAP-2286 (Phase 1) [ Time Frame: 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) ]
   Concentration at the end of infusion (Ceoi)
5. Pharmacokinetics (PK) of 177Lu-FAP-2286 (Phase 1) [ Time Frame: 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) ]
   Area under the curve (AUC)
6. Pharmacokinetics (PK) of 177Lu-FAP-2286 (Phase 1) [ Time Frame: 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) ]
   Clearance (CL)
7. Pharmacokinetics (PK) of 177Lu-FAP-2286 (Phase 1) [ Time Frame: 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) ]
   Volume of distribution (Vd)
8. Pharmacokinetics (PK) of 177Lu-FAP-2286 (Phase 1) [ Time Frame: 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) ]
   Half-half-life (t1/2)
9. Preliminary efficacy of 177Lu-FAP-2286 in advanced solid tumors (Phase 1) [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
   Investigator-assessed objective response by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
10. Duration of response (DOR) (Phase 2) [ Time Frame: From time of initial response until disease progression (up to approximately 2 years) ]
    DOR per RECIST v1.1, as assessed by investigator
11. Progression-free survival (PFS) (Phase 2) [ Time Frame: From first dose of study drug until disease progression (up to approximately 2 years) ]
    Disease progression according to RECIST v1.1, as assessed by investigator, or death due to any cause
12. Overall survival (OS) (Phase 2) [ Time Frame: From first dose of study drug until death (up to approximately 3 years) ]
    Survival assessments conducted via visit or telephone call
13. Further evaluate AEs, SAEs, and clinical laboratory abnormalities of 177Lu-FAP-2286 (Phase 2) [ Time Frame: From first dose of study drug through at least 6-8 weeks after end of treatment (Total Time Frame estimated up to approximately 6 years) ]
    Incidence of adverse events, serious adverse events, and clinical laboratory abnormalities
14. Evaluate AEs and SAEs following administration of Safety of 68Ga-FAP-2286 [ Time Frame: From first dose of study drug through at least 6-8 weeks after end of treatment (up to approximately 1 year) ]
    Incidence of Analysis of adverse events (AEs) and serious adverse events (SAEs)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Patient enrolled in Phase 2 will have one of several specific 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 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.

Contacts and Locations

Contacts

Contact: Clovis Oncology; 1-415-409-7220, 1-844-258-7662; medinfo@clovisoncology.com

Locations

United States, Alabama

UAB Comprehensive Cancer Center; Recruiting

Birmingham, Alabama, United States, 35233

United States, California

UCSF Medical Center; Recruiting

San Francisco, California, United States, 94158

United States, Iowa

University of Iowa Hospitals and Clinics; Recruiting

Iowa City, Iowa, United States, 52242

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

United States, New York

Columbia University Medical Center; Recruiting

New York, New York, United States, 10032

United States, Texas

University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Sponsors and Collaborators

Clovis Oncology, Inc.

Investigators

• Principal Investigator: Thomas Hope, MD; University of California, San Francisco

More Information

• Responsible Party: Clovis Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT04939610
• Other Study ID Numbers: CO-2286-114
• First Posted: June 25, 2021
• Last Update Posted: August 29, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

De-identified datasets for study results will be made available to qualified researchers in compliance with applicable privacy laws and data protection regulations.

Data will be provided by Clovis Oncology.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: Data will be made available to qualified researchers after the primary, secondary, and/or exploratory outcomes of the study are reported or published and for 1 year thereafter.
• Access Criteria: Requests for de-identified datasets will be made available to qualified researchers following submission of a methodologically sound proposal to medinfo@clovisoncology.com.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Clovis Oncology, Inc.:

177Lu-FAP-2286; 68Ga-FAP-2286; theranostic; FAP-2286; FAP; 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

Additional relevant MeSH terms:

Neoplasms