89Zr-DFO-REGN3767 in PET Scans in People With Diffuse Large B Cell Lymphoma (DLBCL)

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04566978

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purposes of this study include:

Looking at the way the body absorbs, distributes, and gets rid of 89Zr-DFO-REGN3767

Finding the best dose amount of 89Zr-DFO-REGN3767

Finding the best time for PET scanning after injection of 89Zr-DFO-REGN3767

Condition or Disease	Intervention/Treatment	Phase
Large B-cell Lymphoma DLBCL	Drug: 89Zr-DFO-REGN3767 Diagnostic Test: PET/CT	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

A Pilot Study of 89Zr-DFO-REGN3767 Anti LAG-3 Antibody Positron Emission Tomography in Patients With Relapsed/Refractory DLBCL

Actual Study Start Date :

Sep 11, 2020

Anticipated Primary Completion Date :

Sep 11, 2022

Anticipated Study Completion Date :

Sep 11, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 Up to 3 participants will be enrolled to receive a single dose of 89Zr-DFO-REGN3767 (total 2mg antibody mass). Participant to undergo 3 PET/CT scans and concurrent blood draws for PK	Drug: 89Zr-DFO-REGN3767 89Zr-DFO-REGN3767 is comprised of the anti-LAG-3 antibody, REGN3767 labeled with the positron-emitter zirconium-89 (89Zr) through the chelator-linker DFO. REGN3767 is an investigational monoclonal antibody that target LAG-3 receptors. Diagnostic Test: PET/CT A PET/CT scan extending from top of skull to feet will be performed to determine the biodistribution. Part A patients will be imaged at three time points post-injection to allow for selection of optimal imaging time and dosimetry determination. For these patients, top of skull to feet scans will be acquired: Within one to four hours following injection of tracer on Day 1 24-72 hours post-injection (Day 2-4) 20-168 hours post-injection (once during days 5-7)
Experimental: Cohort 2 Up to 3 participants will be enrolled to receive a total 5mg of 89Zr-DFO-REGN3767 (+REGN3767) total antibody mass for PK and serial imaging with 3 PET/CT scans	Drug: 89Zr-DFO-REGN3767 89Zr-DFO-REGN3767 is comprised of the anti-LAG-3 antibody, REGN3767 labeled with the positron-emitter zirconium-89 (89Zr) through the chelator-linker DFO. REGN3767 is an investigational monoclonal antibody that target LAG-3 receptors. Diagnostic Test: PET/CT A PET/CT scan extending from top of skull to feet will be performed to determine the biodistribution. Part A patients will be imaged at three time points post-injection to allow for selection of optimal imaging time and dosimetry determination. For these patients, top of skull to feet scans will be acquired: Within one to four hours following injection of tracer on Day 1 24-72 hours post-injection (Day 2-4) 20-168 hours post-injection (once during days 5-7)
Experimental: Cohort 3 Up to 3 participants will be enrolled to receive a total 10mg of 89Zr-DFO-REGN3767 (+REGN3767) total antibody mass for PK and serial imaging with 3 PET/CT scans	Drug: 89Zr-DFO-REGN3767 89Zr-DFO-REGN3767 is comprised of the anti-LAG-3 antibody, REGN3767 labeled with the positron-emitter zirconium-89 (89Zr) through the chelator-linker DFO. REGN3767 is an investigational monoclonal antibody that target LAG-3 receptors. Diagnostic Test: PET/CT A PET/CT scan extending from top of skull to feet will be performed to determine the biodistribution. Part A patients will be imaged at three time points post-injection to allow for selection of optimal imaging time and dosimetry determination. For these patients, top of skull to feet scans will be acquired: Within one to four hours following injection of tracer on Day 1 24-72 hours post-injection (Day 2-4) 20-168 hours post-injection (once during days 5-7)
Experimental: Cohort 4 Up to 3 participants will be enrolled to receive a total 20mg of 89Zr-DFO-REGN3767 (+REGN3767) total antibody mass for PK and serial imaging with 3 PET/CT scans	Drug: 89Zr-DFO-REGN3767 89Zr-DFO-REGN3767 is comprised of the anti-LAG-3 antibody, REGN3767 labeled with the positron-emitter zirconium-89 (89Zr) through the chelator-linker DFO. REGN3767 is an investigational monoclonal antibody that target LAG-3 receptors. Diagnostic Test: PET/CT A PET/CT scan extending from top of skull to feet will be performed to determine the biodistribution. Part A patients will be imaged at three time points post-injection to allow for selection of optimal imaging time and dosimetry determination. For these patients, top of skull to feet scans will be acquired: Within one to four hours following injection of tracer on Day 1 24-72 hours post-injection (Day 2-4) 20-168 hours post-injection (once during days 5-7)

Outcome Measures

Primary Outcome Measures

Biodistribution of 89Zr-DFO-REGN3767 [2 years]
A PET/CT scan extending from top of skull to feet will be performed to determine the biodistribution of 89Zr-DFO-REGN3767
Optimal 89Zr-DFO-REGN3767 mass dose for tumor targeting [2 years]
Determine the optimal 89Zr-DFO-REGN3767 mass dose for tumor targeting
Optimal time for imaging and tumor uptake post 89Zr-DFO-REGN3767 administration [2 years]
Determine the optimal time for imaging and tumor uptake post 89Zr-DFO-REGN3767 administration
Tumor lesion uptake of 89Zr-DFO-REGN3767 and correlate with LAG-3 expression by IHC [2 years]
Evaluate tumor lesion uptake of 89Zr-DFO-REGN3767 and correlate with LAG-3 expression by IHC in tumors will be compared descriptively with other biomarkers of tumor immune environment characterized in biopsies, such as quantitation of IHC score (LAG-3 and / or other immune cell markers), or other biomarker measures.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

A patient must be eligible for DLBCL expansion cohort 9 in study 17-421 and, in addition, meet the following criteria to be eligible for inclusion in the study:

Measurable disease by Lugano criteria, with at least one lesion outside of the liver
Patients must have eGFR >50 mL/min/1.73m2.

Exclusion Criteria:

A patient must be eligible for DLBCL expansion cohort 9 in study 17-421 and, in addition, a patient who meets any of the following criteria will be excluded from the study:

Patients who have permanently discontinued anti-cancer immune modulating therapies due to drug-related toxicity.
Has not yet recovered (i.e. ≤ Grade 1 or baseline) from any acute toxicities from prior anticancer therapy except for laboratory changes as described in inclusion criteria in study 17-421, except as noted. NOTE: Patients with chronic or stable toxicity following approved therapy, such as mild persistent neuropathy, are allowed.
Has received radiation therapy within 14 days of first administration of study drug or has not recovered (i.e. ≤ Grade 1 or baseline) from adverse events, except for laboratory changes as described in inclusion criteria, except as noted. NOTE: Patients with chronic or stable toxicity, such as mild persistent neuropathy, are allowed.
Women who are pregnant, breastfeeding *Postmenopausal women must be amenorrhoeic for at least 12 months in order not to be considered of childbearing potential. Pregnancy testing and contraception are not required for women with documented hysterectomy or tubal ligation. Pregnancy testing and screening will be performed per MSK and Department of Radiology standard pregnancy screening guidelines.