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.

Tracking Information

• First Submitted Date: June 9, 2021
• First Posted Date: June 25, 2021
• Last Update Posted Date: August 29, 2022
• Actual Study Start Date: July 30, 2021
• Estimated Primary Completion Date: July 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 17, 2021)

• 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)
• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 17, 2021)

• 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
• 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
• 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
• 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)
• 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)
• 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)
• 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)
• 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)
• 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
• 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
• 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
• 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
• 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
• 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)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of 177Lu-FAP-2286 in Advanced Solid Tumors (LuMIERE)
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Solid Tumor

Intervention

• 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).
• 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.

Study Arms

• Experimental: Phase 1: Dose Escalation
  Up to 30 patients with solid tumors.
  Interventions:

  • Drug: 68Ga-FAP-2286
  • Drug: 177Lu-FAP-2286
• Experimental: Phase 1: RP2D Expansion Cohort
  Up to 20 patients with solid tumors.
  Interventions:

  • Drug: 68Ga-FAP-2286
  • Drug: 177Lu-FAP-2286
• Experimental: Phase 2: Specific Solid Tumors
  Cohorts of up to 40 patients each with Advanced or Solid Tumors
  Interventions:

  • Drug: 68Ga-FAP-2286
  • Drug: 177Lu-FAP-2286

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 17, 2021): 170
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 1, 2026
• Estimated Primary Completion Date: July 1, 2024 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04939610
• Other Study ID Numbers: CO-2286-114
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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
• Supporting Materials: 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.

• Current Responsible Party: Clovis Oncology, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Clovis Oncology, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Clovis Oncology, Inc.
• Verification Date: August 2022