A Phase 1/2 Study of AMG 701 in Subjects With Multiple Myeloma

Overview

The primary purpose of the phase 1 part of the study is to estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, RP2D) and to confirm the safety and tolerability of the RP2D. The dose escalation part of the study will be conducted at multiple sites and test increasing doses and dosing schedules of AMG 701. This will be followed by Phase 1b dose confirmation and Phase 2 dose expansion parts to gain further efficacy and safety experience with AMG 701. The safety of subjects will be monitored by intensive assessments of vital signs, electrocardiograms, physical examinations, and laboratory tests.

SparkCures ID 915
Trial Phase Phase 1
Enrollment 408 Patients
Treatments
Tags
NCT Identifier

NCT03287908

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

The following criteria is provided for health care professionals.

Inclusion Criteria:

  • Multiple myeloma meeting the following criteria:
    • Pathologically-documented diagnosis of multiple myeloma that is relapsed or is refractory as defined by the following:
      • Relapsed after > or = 3 lines of prior therapy that must include a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and, where approved and available, a CD38-directed cytolytic antibody in combination in the same line or separate lines of treatment OR refractory to PI, IMiD, and CD38- directed cytolytic antibody,
      • Subjects who could not tolerate a PI, IMiDs, or a CD38-directed cytolytic antibody are eligible to enroll in the study.
    • Measurable disease as per IMWG response criteria
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

Exclusion Criteria:

  • Known extramedullary relapse in the absence of any measurable medullary involvement
  • Known central nervous system involvement by multiple myeloma
  • Autologous stem cell transplantation less than 90 days prior to study day 1
  • Known history of primary plasma cell leukemia or evidence of primary or secondary plasma cell leukemia at the time of screening
  • Waldenstrom's macroglobulinemia
  • Prior amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met)
  • Treatment with systemic immune modulators including, but not limited to, nontopical systemic corticosteroids (unless the dose is ≤ 10 mg/day prednisone or equivalent), cyclosporine, and tacrolimus within 2 weeks before study day 1
  • Last anticancer treatment (chemotherapy, IMiD, PI, molecular targeted therapy) < 2 weeks prior to study day 1 or treatment with a therapeutic antibody less than 4 weeks prior to study day 1 as well as systemic radiation therapy within 28 days prior to study day 1 or focal radiotherapy within 14 days prior to study day 1.
  • Prior treatment with any drug or construct that targets BCMA on tumor cells (eg, other bispecific antibody constructs, antibody drug conjugates, or CAR-T cells), other than Group C where prior treatment with GSK2857916 (belantamab mafodotin) is required.

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

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Mayo Clinic (Jacksonville)

Jacksonville, FL

Mayo Clinic (Rochester)

Rochester, MN

Florida
Mayo Clinic (Jacksonville)

Jacksonville, FL

Illinois
Minnesota
Mayo Clinic (Rochester)

Rochester, MN

Missouri
Verified Alvin J. Siteman Cancer Center Washington University Medical Campus

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North Carolina
Texas
Utah
Wisconsin
Verified Medical College of Wisconsin Froedtert Hospital

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International Locations

This trial has active trial locations in countries outside of the United States.

Our system currently only provides clinical trial matching services for myeloma patients in the United States.

You can view this clinical trial's international locations by visiting ClinicalTrials.gov. Please be aware that the government website may include information that is inaccurate and/or out-of-date.

Published Results

A Phase 1 First in Human (FIH) Study of AMG 701, an Anti-B-Cell Maturation Antigen (BCMA) Half-Life Extended (HLE) BiTE® (bispecific T-cell engager) Molecule, in Relapsed/Refractory (RR) Multiple Myeloma (MM)

December 05, 2020

As of July 2, 2020, 75 patients received AMG 701. Patients had a median age of 63 years, a median time since diagnosis of 5.9 years, and a median (range) of 6 (1-25) prior lines of therapy; 27% of patients had extramedullary disease, 83% prior SCT, and 93% prior anti-CD38 Ab; 68% were triple refractory to a PI, an IMiD, and an anti‑CD38 Ab. Median (Q1, Q3) treatment duration was 6.1 (3.1, 15.3) weeks and median follow-up on treatment was 1.7 (1.0, 3.7) months. Patients discontinued drug for PD (n=47), AEs (adverse events, n=4, 3 CRS, 1 CMV / PCP pneumonia), withdrew consent (4), other therapy (1), investigator discretion (1), and CNS disease (1); 17 patients remain on AMG 701.

The most common hematological AEs were anemia (43%), neutropenia (23%), and thrombocytopenia (20%). The most common non-hematological AEs were CRS (61%), diarrhea (31%), fatigue (25%), and fever (25%). CRS was mostly grade 1 (n=19) or 2 (n=21) per Lee Blood 2014 criteria. All grade 3 CRS (n=5, 7%) were assessed as dose-limiting toxicities (DLTs); all were reversible with corticosteroids and tocilizumab, with median duration of 2 days. CRS grade 3 drivers included transient LFT increases in 3 patients and hypoxia in 2 patients. Other DLTs were 1 case each of transient grade 3 atrial fibrillation, transient grade 3 acidosis, and grade 4 thrombocytopenia. Serious AEs (n=29, 39%) included infections (13), CRS (7), and asymptomatic pancreatic enzyme rise (2, no imaging changes, 1 treatment related). There were 4 deaths from AEs, none related to AMG 701 (2 cases of sepsis, 1 of retroperitoneal bleeding, and 1 of subdural hematoma). Reversible treatment-related neurotoxicity was seen in 6 patients, with median duration of 1 day, all grade 1-2, and associated with CRS in 4 patients.

The response rate was 36% (16/45) at doses of 3-12 mg; at ≤1.6 mg (n=27), there was 1 response at 0.8 mg in a patient with low baseline soluble BCMA (sBCMA). With earlier dose escalation with 9 mg, the response rate was 83(5/6, 3 PRs, 2 VGPRs), with 4/5 responders being triple refractory and 1 DLT of grade 3 CRS in this group. Across the study, responses included 4 stringent CRs (3 MRD-negative, 1 not yet tested), 1 MRD-negative CR, 6 VGPRs, and 6 PRs (Table). Median (Q1, Q3) time to response was 1.0 (1.0, 1.9) month, time to best response was 2.8 (1.0, 3.7) months, and response duration was 3.8 (1.9, 7.4) months, with maximum duration of 23 months; responses were ongoing at last assessment in 14/17 patients (Figure). MRD was tested in 4 patients (3 sCR, 1 CR) and all were negative (3 by NGS, 1 by flow); MRD negativity was ongoing at last observations up to 20 months later. AMG 701 exhibited a favorable PK profile in its target patient population of RR MM, with AMG 701 exposures increasing in a dose‑related manner. Patient baseline sBCMA levels were identified as a determinant of AMG 701 free drug exposures; at higher doses, encouraging preliminary responses were seen even at the higher end of baseline sBCMA values.

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