NCT03571828

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

Terminated Phase 1 Results posted Last updated 22 March 2024

What this trial tests

Phase 1 trial testing AMG 562 in Diffuse Large B-cell Lymphoma(DLBCL) in 10 participants. Terminated before completion.

Timeline

29 October 2018

Primary endpoint
12 January 2022

12 January 2022

Quick facts

Lead sponsor	Amgen
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	10
Start date	29 October 2018
Primary completion	12 January 2022
Estimated completion	12 January 2022
Sites	12 locations across Belgium, Canada, United States, Germany

Drugs / interventions tested

• AMG 562 — full drug profile →

Conditions studied

• Diffuse Large B-cell Lymphoma(DLBCL) — all drugs for Diffuse Large B-cell Lymphoma(DLBCL) →
• Mantle Cell Lymphoma (MCL) — all drugs for Mantle Cell Lymphoma (MCL) →
• Follicular Lymphoma (FL) — all drugs for Follicular Lymphoma (FL) →

Sponsor

Amgen — full company profile →

Who can join

Adults 18 to 100, any sex, with Diffuse Large B-cell Lymphoma(DLBCL) or Mantle Cell Lymphoma (MCL). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) Primary · Day 1 to Day 28

Group	Value	95% CI
Cohort 1: AMG 562 0.1 μg	1
Cohort 2: AMG 562 0.3 μg	0

Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) Primary · Up to 2 years

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.

TEAEs

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	8
Cohort 2: AMG 562 0.3 μg	1

Treatment-related TEAEs

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	4
Cohort 2: AMG 562 0.3 μg	0

Disease-related TEAEs

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	1
Cohort 2: AMG 562 0.3 μg	0

Maximum Observed Concentration (Cmax) of AMG 562 Secondary · Day 1

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	0.0460	± 0.0173

Time of Maximum Concentration (Tmax) of AMG 562 Secondary · Day 1

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	1.2	1.0 – 6.1

Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Timepoint (AUClast) of AMG 562 Secondary · Day 1

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	0.658	± 0.426

Half-life (t1/2) of AMG 562 Secondary · Day 22

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	61.2	NA – NA

Objective Response Rate (ORR) Per Lugano Classification Secondary · Day 1 up to 2 years

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

CMR

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	12.5
Cohort 2: AMG 562 0.3 μg	0.0

PMR

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	0.0
Cohort 2: AMG 562 0.3 μg	0.0

Best Overall Response Per Lugano Classification Secondary · Day 1 up to 2 years

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

CMR

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	12.5
Cohort 2: AMG 562 0.3 μg	0.0

PMR

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	0.0
Cohort 2: AMG 562 0.3 μg	0.0

NMR

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	0.0
Cohort 2: AMG 562 0.3 μg	0.0

PMD

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	50.0
Cohort 2: AMG 562 0.3 μg	100.0

Unable to Evaluate or Not Available

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	37.5
Cohort 2: AMG 562 0.3 μg	0.0

Duration of Response (DOR) Secondary · Day 1 up to 2 years

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.

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	NA	± NA

Progression Free Survival (PFS) Secondary · Day 1 up to 2 years

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.

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	0.9	0.6 – 8.1
Cohort 2: AMG 562 0.3 μg	1.0	1.0 – 1.0

Overall Survival (OS) Secondary · Day 1 up to 2 years

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.

Group	Value	95% CI
Cohort 1: AMG 562 0.1 µg	NA	1.7 – NA
Cohort 2: AMG 562 0.3 μg	NA	NA – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Mortality: Day 1 up to end of study, median time on study was 3.14 months (min: 0.30; max: 22.97) Adverse events: Day 1 up to 30 days after last dose, median time was 1.71 months (min: 1.35; max 22.64). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1: AMG 562 0.1 μg

Serious: 3/8 (38%)

Deaths: 2/9

Cohort 2: AMG 562 0.3 μg

Serious: 1/1 (100%)

Deaths: 0/1

Serious adverse events (6 terms)

Reaction	System	Cohort 1: AMG 562 0.1 μg	Cohort 2: AMG 562 0.3 μg
Neutropenia	Blood and lymphatic system disorders	—	—
Pseudomonal sepsis	Infections and infestations	—	—
Encephalopathy	Nervous system disorders	—	—
Panic attack	Psychiatric disorders	—	—
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (68 terms — click to expand)

Reaction	System	Cohort 1: AMG 562 0.1 μg	Cohort 2: AMG 562 0.3 μg
Pyrexia	General disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Hypotension	Vascular disorders	—	—
Sinus tachycardia	Cardiac disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Chills	General disorders	—	—
Dizziness	Nervous system disorders	—	—
Headache	Nervous system disorders	—	—
Neutropenia	Blood and lymphatic system disorders	—	—
Tachycardia	Cardiac disorders	—	—
Abdominal distension	Gastrointestinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Dysphagia	Gastrointestinal disorders	—	—
Oesophageal pain	Gastrointestinal disorders	—	—
Chest pain	General disorders	—	—
Fatigue	General disorders	—	—
Cytokine release syndrome	Immune system disorders	—	—
Pneumonia	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—
Fall	Injury, poisoning and procedural complications	—	—
Blood cholesterol increased	Investigations	—	—
Blood creatinine increased	Investigations	—	—
Blood glucose increased	Investigations	—	—
C-reactive protein increased	Investigations	—	—
Neutrophil count decreased	Investigations	—	—
Oxygen saturation decreased	Investigations	—	—
Serum ferritin increased	Investigations	—	—
Weight decreased	Investigations	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Bone pain	Musculoskeletal and connective tissue disorders	—	—
Joint instability	Musculoskeletal and connective tissue disorders	—	—

Most-reported serious reactions: Neutropenia, Pseudomonal sepsis, Encephalopathy, Panic attack, Chronic obstructive pulmonary disease, Dyspnoea.

Data from ClinicalTrials.gov NCT03571828 adverse events section.

Sponsor's own description

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 \[RP2D\])

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Emerging new therapeutic antibody derivatives for cancer treatment.
   Jin S, Sun Y, Liang X, Gu X, et al · · 2022 · cited 304× · PMID 35132063 · DOI 10.1038/s41392-021-00868-x
2. Bispecific Antibodies: From Research to Clinical Application.
   Ma J, Mo Y, Tang M, Shen J, et al · · 2021 · cited 199× · PMID 34025638 · DOI 10.3389/fimmu.2021.626616
3. The landscape of bispecific T cell engager in cancer treatment.
   Zhou S, Liu M, Ren F, Meng X, et al · · 2021 · cited 172× · PMID 34039409 · DOI 10.1186/s40364-021-00294-9
4. New agents and regimens for diffuse large B cell lymphoma.
   Wang L, Li LR, Young KH. · · 2020 · cited 109× · PMID 33317571 · DOI 10.1186/s13045-020-01011-z
5. Overcoming the challenges associated with CD3+ T-cell redirection in cancer.
   Singh A, Dees S, Grewal IS. · · 2021 · cited 82× · PMID 33469153 · DOI 10.1038/s41416-020-01225-5
6. Biology drives the discovery of bispecific antibodies as innovative therapeutics.
   Nie S, Wang Z, Moscoso-Castro M, D'Souza P, et al · · 2020 · cited 79× · PMID 33928225 · DOI 10.1093/abt/tbaa003
7. Bispecific, T-Cell-Recruiting Antibodies in B-Cell Malignancies.
   Lejeune M, Köse MC, Duray E, Einsele H, et al · · 2020 · cited 70× · PMID 32457743 · DOI 10.3389/fimmu.2020.00762
8. Bispecific antibodies in cancer therapy: Target selection and regulatory requirements.
   Sun Y, Yu X, Wang X, Yuan K, et al · · 2023 · cited 62× · PMID 37719370 · DOI 10.1016/j.apsb.2023.05.023