Dose Escalation Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma

What's the purpose of this trial?

The purpose of this study is to characterize the safety of Talquetamab and to determine the recommended Phase 2 dose(s) (RP2Ds) and dosing schedule assessed to be safe for Talquetamab (Part 1 [Dose Escalation]) and to further characterize the safety of Talquetamab at the recommended Phase 2 dose(s) (RP2Ds) (Part 2 [Dose Expansion]).

This trial is currently open and accepting patients.


What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

  • Documented initial diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) diagnostic criteria
  • Part 1: Participants with measurable multiple myeloma who have progressed on, or could not tolerate, all available established therapies. Part 2: Participants with multiple myeloma measurable by central laboratory assessment who have progressed on, or could not tolerate, all available established therapies; Serum monoclonal paraprotein (M-protein) level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) or urine M-protein level >=200 milligram per 24 hours (mg/24 h) or light chain multiple myeloma without measurable disease in the serum or the urine: serum immunoglobulin free light chain (FLC) >= 10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio; If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (Beta human chorionic gonadotropin [beta-hCG]) or urine
  • Sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, and is willing to and able participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease

Exclusion Criteria:

  • Vaccinated with live, attenuated vaccine within 4 weeks or as recommended by the product manufacturer prior to the first dose, during treatment, or within 100 days of the last dose of Talquetamab
  • Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
  • Received a cumulative dose of corticosteroids equivalent to greater than or equal to ( >=) 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
  • An allogenic stem cell transplant within 6 months before first dose of study drug. Participants who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease (GVHD); and/or an autologous stem cell transplant less than or equal to (<=) 12 weeks before first dose of study drug
  • Documented history of central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, whole body magnetic resonance imaging (MRI) and lumbar cytology are required

Additional Trial Information

Phase 1

Enrollment: 185 patients (estimated)

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Published Results

Updated results of a phase 1, first-in-human study of talquetamab, a G protein-coupled receptor family C group 5 member D (GPRC5D) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM)

May 28, 2021

  • As of Feb 8, 2021, 174 pts received talquetamab, 102 by IV and 72 by SC; in parts 1 and 2, 28 pts were treated at the RP2D, identified as weekly SC 405 µg/kg, with 10.0 and 60.0 µg/kg step-up doses.
  • Patients treated at the RP2D had a median age of 61.5 y (range 46–80) and a median of 5.5 prior lines of therapy (range 2–14; 100%/79% triple-class/penta-drug exposed; 71%/18% triple-class/penta-drug refractory; 86% refractory to last line of therapy; 21% with prior B-cell maturation antigen–directed therapy).
  • No dose-limiting toxicities occurred at the RP2D in part 1.
  • Most common AEs at the RP2D were:
    • CRS (79%; grade 3 4%; median time to onset: day after SC injection),
    • neutropenia (64%; grade 3/4 54%),
    • anemia (57%; grade 3/4 29%) and
    • dysgeusia (57%; all grade 1/2);
    • infections were reported in 32% of patients (grade 3/4 4%) and neurotoxicity in 7% (grade 3/4 0).
  • In all, 75% of pts dosed at the RP2D had skin-related AEs (grade 3/4 0), including 18% with nail disorders.
  • The overall response rate at the RP2D in response-evaluable pts (n = 24) was 63%, with 50% reaching very good partial response or better; 9/17 (53%) evaluable triple-class refractory pts and 3/3 (100%) penta-drug refractory pts had a response.
  • Median time to first confirmed response at the RP2D was 1.0 mo (range 0.2–3.8); responses were durable and deepened over time (median follow-up 6.2 mo [range 2.7–9.7+] for responders at the RP2D).
  • At the RP2D, exposure was maintained over the maximum EC90 target level from an ex vivo cytotoxicity assay, and consistent T cell activation was seen.
A Phase 1, First-in-Human Study of Talquetamab, a G Protein-Coupled Receptor Family C Group 5 Member D (GPRC5D) x CD3 Bispecific Antibody, in Patients with Relapsed and/or Refractory Multiple Myeloma (RRMM)Clinically Relevant Abstract

December 02, 2020

As of 20 Jul 2020, 137 pts had received talquetamab; 102 by IV (0.5 – 180 µg/kg) and 35 by SC (5 – 800 µg/kg) dosing. Median age was 64 years (33 – 80; 31% were ≥70) and 22% had ISS stage III disease at study entry. Median number of prior therapies was 6 (2 – 20) over a median of 6.5 years (0.9 – 27) since diagnosis, 85% were refractory to last line of therapy, 79% triple-class refractory, 73% penta-drug exposed, and 31% penta-drug refractory. 13 (10%) pts had received selinexor and 21 (15%) had prior BCMA-directed therapy.

Most frequently reported all grade AEs were anemia (50%), CRS (47%), neutropenia (45%), and lymphopenia (40%). Most common grade 3 – 4 AEs were lymphopenia (37%), anemia (27%), and neutropenia (25%). CRS was mostly grade 1 – 2 except for 5 pts with grade 3 CRS (˂8% of pts with CRS) that occurred with IV dosing; only grade 1 – 2 CRS was seen with SC dosing. CRS was generally confined to the first cycle with median time to onset of 1 day (1 – 3) for IV and 2 days (1 – 5) for SC dosing. Treatment-related neurotoxicity was reported in 7 (5%) pts (all resolved/resolving; median duration of 2 days [1 – 9]): 4 had grade 1 – 2 events and 3 had grade 3 events of delirium (n=1), decreased level of consciousness (n=1), or confusion (n=1). Six of 7 pts had neurotoxicity that occurred in the context of CRS, including all 3 grade 3 events. Infections were reported in 37% of pts (8% grade 3 – 4). Infusion related reactions (IV; 15%) and injection site reactions (SC; 14%) were grade 1 – 2 and generally occurred in cycle 1. Two dose-limiting toxicities were observed: clinically asymptomatic grade 4 increased lipase in the setting of a pancreatic plasmacytoma (7.5 µg/kg IV) and grade 3 maculopapular rash (135 µg/kg SC). The maximum tolerated dose (MTD) has not been defined.

Overall response rate (ORR) for IV doses of 20 – 180 µg/kg was 78% (14/18; 2 pending confirmation); 6/6 responded at the 60 µg/kg IV dose. ORR for SC doses of 135 – 405 µg/kg was 67% (8/12); 3/4 responded at the 405 µg/kg SC dose. Responses were noted starting at 1.0 µg/kg, were rapid at a median of 1 month (0.2 – 3), and durable with median not reached in 36/46 (4 pts with response 15+ months; longest at 23+ months). Data at higher doses are immature, and results will be updated at the meeting.

Trial Locations

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Alabama

UAB Comprehensive Cancer Center University of Alabama at Birmingham

Birmingham, AL

Open and Accepting

California

City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting

New York

Mount Sinai Hospital Tisch Cancer Institute

New York, NY

Open and Accepting

Tennessee

Sarah Cannon TriStar Centennial Medical Center

Nashville, TN

Open and Accepting
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