Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma, Large B-Cell, Diffuse

Lymphoma

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

B-cell Lymphoma

Diffuse Large B-Cell Lymphoma

Lymphosarcoma

Mantle Cell Lymphoma

Follicular Lymphoma

All Drugs and Chemicals

Antibodies

Immunoglobulins

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).

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.

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

AMG 562

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 \[RP2D\])

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

A Phase 1, First-in-Human, Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 562 in Subjects With Relapsed / Refractory Diffuse Large B-cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

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.

ORR was defined as the percentage of participants with a confirmed complete metabolic response (CMR) or partial metabolic response (PMR) as defined by Lugano Classification.

Per the Lugano Classification, positron emission tomography-computed tomography (PET-CT) were defined on the 5-point scale as scores 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake \</= mediastinum; and 3 = uptake \> mediastinum but \</= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions).

CMR: score of 1, 2 or 3 in nodal or extranodal sites with or without a residual mass.

PMR: score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size.

Per the Lugano Classification, positron emission tomography-computed tomography (PET-CT) were defined on the 5-point scale as scores 1, 2, or 3 (where 1 = no uptake above background; 2 = uptake \</= mediastinum; and 3 = uptake \> mediastinum but \</= liver) and PET-positive scans, as scores of 4 or 5 (where 4 = uptake moderately higher than liver; 5 = uptake markedly higher than liver and/or new lesions).

CMR: score of 1, 2 or 3 in nodal or extranodal sites with or without a residual mass.

PMR: score of 4 or 5 with reduced uptake compared with baseline and residual mass(es) of any size.

No metabolic response (NMR): score of 4 or 5 with no obvious change in fluorodeoxyglucose (FDG) uptake.

Progressive metabolic disease (PMD): score 4 or 5 in any lesion with an increase in intensity of FDG uptake from baseline (and/or new FDG-avid foci consistent with lymphoma).

DOR was defined as the time from the date of an initial objective response per Lugano classification to the earlier of progression or death. Participants who had not ended their response at the time of analysis had DOR censored at their last disease assessment date.

PFS was defined as the interval from Day 1 to the earlier of a lymphoma progression or death from any cause; otherwise, PFS was censored at the last radiographic assessment date. If a participant had no post baseline radiographic assessment and a vital status of alive or unknown, PFS was censored at Day 1.

OS was defined as the time from the date of Day 1 until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was alive.

Amgen

Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug. Mortality reporting is reported for all participants enrolled.

Participants with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), or follicular lymphoma (FL) received AMG 562 0.1 μg administered as once weekly intravenous (IV) infusions for up to approximately 8 months.

Cohort 1: AMG 562 0.1 μg

Participants with relapsed/refractory DLBCL, MCL, or FL received AMG 562 0.3 μg administered as once weekly IV infusions for up to approximately 8 months.

Cohort 2: AMG 562 0.3 μg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Safety Analysis Set: All participants who received at least one dose of investigational product.

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.

Study Director

DLT Analysis Set: all participants who either experienced DLTs or completed 28 days of DLT observational period and did not experience DLTs.

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

TEAEs

Treatment-related TEAEs

Disease-related TEAEs

Cohort 1: AMG 562 0.1 µg

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

Pharmacokinetic (PK) Analysis Set: all participants who have received at least 1 dose of AMG 562 and have at least 1 PK sample collected.

Maximum Observed Concentration (Cmax) of AMG 562

Time of Maximum Concentration (Tmax) of AMG 562

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

Half-life (t1/2) of AMG 562

Objective Response Rate (ORR) Per Lugano Classification

Unable to Evaluate or Not Available

Best Overall Response Per Lugano Classification

Safety Analysis Set - Objective Responders: All participants who received at least one dose of investigational product and had a CMR or PMR.

Spots Global Cancer Trial Database for 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

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial