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|Amgen Announces First-In-Human Data Evaluating Investigational Novel BiTE® Immunotherapies AMG 420 And AMG 330 At ASH 2018|
BiTE® antibody construct technology, pioneered by
"Building on our success with the only approved BiTE® immunotherapy available for patients,
ASH Abstract #1010: Treatment with AMG 420, an anti-B-Cell Maturation Antigen (BCMA) Bispecific T-cell Engager (BiTE®) Antibody Construct, Induces Minimal Residual Disease (MRD) Negative Complete Responses in Relapsed and/or Refractory (R/R) Multiple Myeloma (MM) Patients: Results of a First-in-Human (FIH) Phase 1 Dose Escalation Study
The data shared at ASH were the first presentation of all endpoints from this Phase 1 dose-escalation trial of AMG 420 in patients with relapsed and/or refractory multiple myeloma. The objectives of the study included assessment of safety, tolerability and anti-tumor activity of AMG 420 per
In the study, 42 patients with relapsed and/or refractory multiple myeloma who had progression after at least two prior lines of treatment (including a proteasome inhibitor and an immunomodulatory imide drug) received AMG 420 at varying doses [0.2 to 800 µg/day (d)]. AMG 420 induced clinical responses in 13 patients, including complete responses (CR) in seven patients. Four patients treated at the 400 µg/d dose achieved minimal residual disease (MRD) negative complete responses, meaning that no cancer cells were detectable in the bone marrow. The objective response rate at 400 µg/d was 70 percent (seven of 10 patients), with six patients still responding up to 7.5 months. One dose-limiting toxicity was observed up to the 400 µg/d dose (peripheral polyneuropathy, which improved to baseline after intravenous immunoglobulin and corticosteroid treatment).
Of those patients with serious adverse events (AEs) (n=20, 48 percent), 17 required hospitalization and four had prolonged hospitalization. Serious AEs included infections (n=12), peripheral polyneuropathy (n=2), and one each of liver failure, cardiac failure, edema, biliary obstruction, spinal cord compression, renal failure and weight loss. Treatment-related serious AEs included polyneuropathy (n=2, both grade 3) and edema (n=1, grade 3). Cytokine release syndrome (CRS) was seen in 16 patients (grade 1, n=13; grade 2, n=2; grade 3, n=1). In this study, 800 µg/d was determined to not be tolerable, as two out of the three patients treated at this dose experienced dose-limiting toxicities.
Two patients died during the course of the study from AEs not considered treatment-related. One patient died after the first cycle of treatment from acute respiratory distress due to concurrent flu and aspergillosis. The second patient died from liver failure secondary to a viral infection during the course of treatment.
"These first-in-human data of a BCMA-targeting BiTE® immunotherapy showed encouraging evidence of AMG 420 activity, with no major toxicities up to the 400 µg/d dose in patients with relapsed and/or refractory multiple myeloma who received a median of four prior therapies," said
Additionally, AMG 420 was granted Fast Track Designation by the
ASH Abstract #25: A Phase 1 First-in-Human Study of AMG 330, an Anti-CD33 Bispecific T-cell Engager (BiTE®) Antibody Construct, in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
In a separate first-in-human Phase 1 dose escalation study, 40 patients with relapsed or refractory AML were enrolled to receive AMG 330 in 12 dose cohorts with a target dose range of 0.5 to 480 µg/d. The study objectives were to evaluate the safety, pharmacokinetics and pharmacodynamics of AMG 330 and to estimate the maximum tolerated dose. Results showed that two patients in the trial achieved a CR at the 240 µg/d dose and two patients achieved a CR with incomplete blood count recovery, one at the 240 µg/d dose and one at the 120 μg/d dose. The CRs were not sustained beyond one cycle of treatment.
Patients in the trial received a median of one (range: 1-6) cycle with AMG 330; the majority of patients discontinued treatment for disease progression. Other reasons for study discontinuation included AEs (n=6, 2 treatment-related) and patient request (n=2).
Serious AEs were seen in 73 percent of patients (treatment-related in 17 patients). The most common serious AEs seen in more than one patient included CRS (n=11), febrile neutropenia (n=7), pneumonia (n=4), leukopenia (n=4), pyrexia (n=3), thrombocytopenia (n=3) and subdural hematoma (n=2). One patient died on study due to AML progression and one due to intracranial hemorrhage (neither treatment-related). There were dose-limiting toxicities of grade 2 CRS and grade 4 ventricular fibrillation with a target dose of 480 μg/d administered as a single-step regimen.
"The majority of adult AML patients will not be cured with standard chemotherapy, underscoring the need for innovative treatment options for those who have relapsed or are refractory to currently available treatments1," said
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