Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 562 in Subjects With r/r Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma

NCT03571828 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 20170533
• Study Type: interventional
• Target: 10
• Locations: 4 countries
• Sites: 12

Brief Summary

Evaluate the safety and tolerability of AMG 562 in adult subjects with DLBCL, MCL, or FL. Estimate the maximum tolerated dose (MTD) and/or a biologically active dose (e.g., recommended phase 2 dose \[RP2D\])

Conditions

Diffuse Large B-cell Lymphoma(DLBCL); Mantle Cell Lymphoma (MCL); Follicular Lymphoma (FL)

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)

  Day 1 to Day 28

• Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

  An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that occurred after receiving at least 1 dose of treatment. Treatment-related TEAEs were those considered related to study treatment by the investigator. Disease-Related TEAEs were events (serious or non-serious) anticipated to occur in the study population due to the underlying disease. Any clinically significant changes in vital signs, physical examinations, electrocardiograms (ECG)s and clinical laboratory tests were recorded as TEAEs.

  Up to 2 years

Secondary Outcomes (9)

• Maximum Observed Concentration (Cmax) of AMG 562

  Day 1

• Time of Maximum Concentration (Tmax) of AMG 562

  Day 1

• Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Timepoint (AUClast) of AMG 562

  Day 1

• Half-life (t1/2) of AMG 562

  Day 22

• Objective Response Rate (ORR) Per Lugano Classification

  Day 1 up to 2 years

Study Arms (2)

Part 1: Dose Exploration

EXPERIMENTAL

Dose exploration cohorts to estimate the MTD, safety, tolerability, and PK of different doses of AMG 562 in subjects with relapsed/refractory DLBCL, MCL or FL using a Bayesian logistic regression model (BLRM; Neuenschwander et al, 2008).

Drug: AMG 562

Part 2: Dose Expansion

EXPERIMENTAL

dose expansion part to gain further clinical experience, safety and efficacy data for AMG 562 in subjects with relapsed / refractory DLBCL. The dose to be evaluated will be at or below the MTD estimated in the dose exploration cohorts.

Drug: AMG 562

Interventions

AMG 562 DRUG

AMG 562 is a BiTE® antibody construct that targets CD19 and is intended for the treatment of patients with B-cell malignancies.

Part 1: Dose Exploration; Part 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures
• Age ≥ 18 at the time of informed consent.
• Biopsy proven B-NHL including:
• DLBCL, which also includes DLBCL that represents transformation of indolent NHL (including follicular, marginal zone, and lymphoplasmacytic lymphoma excluding chronic lymphocytic leukemia or Hodgkin Lymphoma) and DLBCL with alterations of MYC and BCL2 and/or BCL6 also described as double-hit and triple-hit lymphomas.
• MCL Presentations of these histologies with substantial occurrence of malignant cells into the bloodstream (lymphocyte count ≥ 7 x 10\^9/L) including all leukemic presentations are excluded.
• The following histologies are not eligible:
• Lymphoblastic lymphoma Burkitt lymphoma Any histologies not specifically mentioned must be discussed with the Medical Monitor
• Subjects with transformation of indolent lymphoma must have received therapy after a diagnosis of transformation that is appropriate for aggressive histology.
• \- Subjects who received prior CD19-targeting treatment are allowed (CAR-T cell therapy is excluded). A biopsy following CD19-targeting treatment is required unless no lesions are accessible or the risk of the biopsy is deemed too high by the investigator For Part 2 (Expansion in patients with DLBCL): only biopsy proven DLBCL (biopsy proven at least at primary diagnosis), including DLBCL that represents transformation of indolent NHL (including follicular, marginal zone, and lymphoplasmacytic lymphoma excluding chronic lymphocytic leukemia or Hodgkin Lymphoma) are eligible. Other histologies are not eligible.
• Presentations of these histologies with substantial occurrence of malignant cells into the bloodstream (lymphocyte count ≥ 7 x 10\^9/L) including all leukemic presentations are excluded.
• Subjects who received prior CD19-targeting treatment are allowed (CAR-T cell therapy is excluded) A biopsy following CD19-targeting treatment is required unless no lesions are accessible or the risk of the biopsy is deemed too high by the investigator - For DLBCL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after two or more prior treatments, with at least one treatment consisting of standard multiagent chemotherapy containing an anthracycline AND an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP (14 or 21), R-CHOEP, and DA-R-EOCH.
• For FL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after three or more prior treatments, with at least one treatment consisting of a standard chemotherapy containing an approved anti-CD20 agent.
• Examples of appropriate therapy include but are not limited to R-CHOP, R-CVP, and BR.
• For MCL: Refractory (no prior CR/CMR) to first or later line of treatment or relapsed (prior CR/CMR) after three or more prior treatments, with at least one treatment consisting of a standard chemotherapy containing an approved anti-CD20 agent. Examples of appropriate therapy include but are not limited to R-CHOP, BR and hyper-CVAD alternating with R-MTX/Ara-C.
• For subjects with refractory B-NHL and who have received radiotherapy, PET positivity should be demonstrated no less than 6 weeks after the last dose of radiotherapy

You may not qualify if:

• Treatment within 30 days prior to enrollment with another investigational device or drug (interventional clinical study / studies). Other investigational procedures while participating in this study are excluded (observational studies are permitted).
• Prior anti-cancer therapy as specified below:
• At least 6 weeks must have elapsed since any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc) before the first dose of AMG 562.
• Other targeted anti-cancer therapy (chemotherapy, molecular targeted therapy, steroids) within 14 days or 5 half lives (which ever is longer) prior to first dose of AMG 562. Patients requiring continued treatment due to aggressive disease may only be included if there is agreement by both the investigator and the Amgen Medical Monitor.
• Radiation therapy completed within 28 days prior to first dose of AMG 562.
• Autologous HSCT within six weeks prior to start of AMG 562 treatment.
• At least 4 weeks must have elapsed since any prior treatment with antibody therapy (exception immune checkpoint inhibitors) before the first dose of AMG 562.
• Prior CD19-directed CAR-T cell therapies
• Prior allogeneic HSCT.
• For Part 2 (Expansion in patients with DLBCL): fluorodeoxyglucose non-avid patients.
• Baseline electrocardiogram (ECG) QTc \> 470 msec.
• Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy. Patient may be included if the treatment is discontinued more than 3 months prior to the first dose of AMG 562 at a low likelihood of relapse AND if there is agreement by both the investigator and the Amgen Medical Monitor.
• Presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
• Evidence of CNS involvement by NHL.
• Known infection with human immunodeficiency virus (HIV).

Sponsors & Collaborators

• Amgen: lead

Study Sites (12)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Klinikum der Universität München Campus Großhadern

München, 81377, Germany

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97080, Germany

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Amgen decided not to continue development of AMG 562 because of a business decision and not because of safety reasons. No conclusions can be drawn due to the small sample size of this study.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2018
• First Posted: June 28, 2018
• Study Start: October 29, 2018
• Primary Completion: January 12, 2022
• Study Completion: January 12, 2022
• Last Updated: March 22, 2024
• Results First Posted: March 22, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (7); CA (1); BE (1); DE (3)