Study of Modakafusp Alfa in Combination with Daratumumab Subcutaneous in Multiple Myeloma Patients

• Research type

  Research Study

• Full title

  A Phase 1/2a Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Modakafusp Alfa in Combination With Daratumumab Subcutaneous in Patients With Relapsed or Refractory Multiple Myeloma

• IRAS ID

  1006706

• Contact name

  Isha Majmudar

• Contact email

  isha.majmudar@takeda.com

• Sponsor organisation

  Takeda Development Center Americas, Inc.

• Eudract number

  2022-002169-14

• Research summary

  Summary of Research
  This is a global study, open in about 40 centres worldwide, aimed at assessing the safety/tolerability and efficacy of the combination of modakafusp alfa with daratumumab subcutaneous (SC) in patients with multiple myeloma (MM), relapsing after 1 or more lines of therapy. Modakafusp alfa is a new investigational drug that is not approved anywhere. It is a biological agent to enhance the immune system which is critical to kill cancer cells. Daratumumab SC is an approved drug for the treatment of MM. This is the first time that these 2 drugs are combined to assess the safety/tolerability and anti-myeloma activity of this combination.. The study consists of 2 parts:

  - Part 1: Modakafusp alfa dose will be steadily increased to define the tolerable dose(s), in terms of safety for the combination with daratumumab SC. The different doses for this part were chosen based on the known safety profile of modakafusp alfa as a single agent and the potential overlapping toxicities with daratumumab SC.
  - Part 2: We will select 2 doses of interest among those tested in part 1 and compare them to further optimise dose selection.
  Besides safety/tolerability and efficacy, other factors we will assess to select the best dose are pharmacokinetic (what the participant’s body does to the drug, how fast it is eliminated) and pharmacodynamic (what the drug does to the participant’s body). This information will be gathered using blood and/or bone marrow samples at different time points.

  We estimate that 58 patients will be enrolled, but this could vary depending on the data observed. The total length of participation will depend on the patient’s disease response to the combination but could be up to 5 years.

  Summary of Results
  A total of 15 patients with relapsed/refractory multiple myeloma were enrolled into phase 1 dose escalation of the study. Eight patients had a confirmed best overall response of partial response or better. The most frequently occurring adverse events were: thrombocytopenia (9 [60.0%] patients), neutropenia (8 [53.3%] patients), fatigue (6 [40.0%] patients), and anaemia (5 [33.3%] patients). The most frequently occurring Grade 3 and Grade 4 hematological TEAEs that occurred in more than 1 patient were in the SOC of blood and lymphatic disorders (6 [40.0%] patients with Grade 3 TEAEs and 2 [13.3%] patients with Grade 4 TEAEs), of which Grade 3 and Grade 4 neutropenia were experienced by 5 (33.3%) patients and 2 (13.3%) patients, respectively. Grade 3 thrombocytopenia and anaemia were also experienced by 3 (20.0%) patients each; Grade 4 thrombocytopenia was experienced by 2 (13.3%) patients, and Grade 3 febrile neutropenia was experienced by 1 (6.7%) patient. No nonhematological Grade 3 and 4 TEAE occurred in more than 1 patient each. One on-study death (due to altered general condition/deterioration of general condition and progressive disease occurred in the 240 mg group; it was considered by investigator to be related to the disease under study and related complications. Three (20.0%) patients had at least 1 serious adverse event (SAE). No single SAE occurred in more than 1 patient. The dose of modakafusp alfa was interrupted due an AE in 2 (13.3%) patients; daratumumab was interrupted due to an AE in 2 (13.3%) patients; and both drugs were interrupted due to an AE in 1 (6.7%) patient. Two (13.3%) patients experienced an adverse event of special interest (AESI) for infusion related reaction signs and symptoms related to modakafusp alfa, and 1 (6.7%) patient each experienced an AESI for IRR signs and symptoms related to daratumumab or both study drugs (modakafusp alfa and daratumumab). No adverse trends were noted for laboratory evaluations, vital signs, electrocardiograms or Eastern cooperative oncology group performance scores. Neutropenia and thrombocytopenia were reversible and decreased with longer follow up.

• REC name

  Wales REC 2

• REC reference

  23/WA/0004

• Date of REC Opinion

  20 Jul 2023

• REC opinion

  Further Information Favourable Opinion