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

• Sponsor: Clovis Oncology, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04939610
• Collaborator: (none)
• Enrollment: 170
• Locations: 6
• Arms: 3
• Anticipated Duration (Months): 58.1
• Patients Per Site: 28.3
• Patients Per Site Per Month: 0.5

Study Details

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; Drug: 177Lu-FAP-2286	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Anticipated 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: Jul 30, 2021
• Anticipated Primary Completion Date: Jul 1, 2024
• Anticipated Study Completion Date: Jun 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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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) [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 [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

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	UAB Comprehensive Cancer Center	Birmingham	Alabama	United States	35233
2	UCSF Medical Center	San Francisco	California	United States	94158
3	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
4	Mayo Clinic	Rochester	Minnesota	United States	55905
5	Columbia University Medical Center	New York	New York	United States	10032
6	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Clovis Oncology, Inc.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Clovis Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT04939610
• Other Study ID Numbers: CO-2286-114
• First Posted: Jun 25, 2021
• Last Update Posted: Aug 11, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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

Study Results

No Results Posted as of Aug 11, 2022