A Study of Modakafusp Alfa Together With Daratumumab Adults With Relapsed or Refractory Multiple Myeloma (iinnovate-3)

Teva Branded Pharmaceutical Products R&D LLC

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Modakafusp Alfa; Drug: Daratumumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05590377

TAK-573-2001

2022-002169-14 (EudraCT Number)

Details and patient eligibility

About

The main aim of this study is to determine safety and tolerability of modakafusp alfa given together with daratumumab to find out the best treatment dose. Another aim of this study is to learn more about the characteristics of modakafusp alfa.

Full description

The drug being tested in this study is called modakafusp alfa (TAK-573). Modakafusp alfa is being tested to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy in combination with daratumumab in participants with relapsed or refractory multiple myeloma (RRMM). The study will consist of 2 phases: Phase 1 Dose Escalation and a Phase 2a Dose Finding.

The study will enroll approximately 58 patients. Approximately 18 participants will be enrolled in the Phase 1 Dose Escalation/De-escalation and two dose levels of modakafusp alfa in combination with daratumumab SC will be selected to be further explored in the randomized Phase 2a Dose Finding part of the study wherein, approximately 40 participants will be randomly assigned by chance (like flipping a coin) to one of the two treatment groups:

• Phase 2a Dose Finding: Modakafusp Alfa (DL1) + Daratumumab
• Phase 2a Dose Finding: Modakafusp Alfa (DL2) + Daratumumab This multi-center trial will be conducted worldwide. The overall time to participate in this study is approximately 60 months. Participants who discontinue study drug treatment for reasons other than progressive disease will continue progression-free survival (PFS) follow-up every 4 weeks from the end of treatment (EOT) visit until the occurrence of progressive disease, death, the start of subsequent systemic antineoplastic therapy, study termination, whichever occurs first.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Documented multiple myeloma (MM) diagnosis per IMWG criteria.

2. Measurable disease, defined as at least 1 of the following:

   1. Serum M protein ≥0.5 grams per deciliter [g/dL] (≥5 g/L) on serum protein electrophoresis (SPEP).
   2. Urine M protein ≥200 mg/24 hours on urine protein electrophoresis (UPEP).
   3. Serum free light chain (FLC) assay with involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.

3. For participants in the Phase 1 Dose Escalation only:

   Must have received at least 3 prior lines of therapy, including at least 1 proteosome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-CD38 monoclonal antibody (mAb) drug; or who are triple refractory to a PI, an IMiD, and an anti-CD38 mAb drug, regardless of the number of prior line(s) or therapy.

4. For participants in Phase 2a Dose Finding only:

   1. Received 1 to 3 prior line(s) of antimyeloma therapy.
   2. Must be refractory to prior lenalidomide treatment.
   3. Participants must be sensitive (nonrefractory) or naïve to prior anti-CD38 mAb treatment.
   4. Documented progressive disease on or after the last regimen.
   5. Participants must have PR or better to at least 1 line of prior therapy.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening.

Exclusion criteria

1. Prior exposure to modakafusp alfa.
2. Participant has polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, plasma cell leukemia, or lymphoplasmacytic lymphoma.
3. Participant has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to NCI CTCAE, Version 5 Grade ≤1 or baseline, except for alopecia.
4. Previous allogeneic stem cell transplant at any time or autologous stem cell transplant (ASCT) within 12 weeks of planned start of dosing.
5. Seropositive for hepatitis B, or known history of seropositivity for hepatitis C or of seropositivity for human immunodeficiency virus (HIV).
6. Participant has congestive heart failure (New York Heart Association Grade ≥II), cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris, clinically significant arrhythmia requiring therapy including anticoagulants, or clinically significant uncontrolled hypertension.
7. Participant has QT interval corrected by the Fridericia method >480 milliseconds [msec] (Grade ≥2).
8. Participant has a chronic condition that will require the chronic use of systemic corticosteroids >10 milligrams per day (mg/d) of prednisone or equivalent on top of any required corticosteroids for multiple myeloma (MM).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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15 participants in 5 patient groups

Phase 1 (Dose Escalation) Modakafusp Alfa 80 mg + Daratumumab

Experimental group

Description:

Modakafusp alfa 80 mg, infusion, intravenously (IV), once every 4 weeks (Q4W) with daratumumab 1800 mg, subcutaneously (SC), once weekly (QW) in Cycles 1 and 2, twice weekly (Q2W) in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression.

Treatment:

Drug: Daratumumab

Drug: Modakafusp Alfa

Phase 1 (Dose Escalation) Modakafusp Alfa 120 mg + Daratumumab

Experimental group

Description:

Modakafusp alfa 120 mg, infusion, IV, Q4W with daratumumab 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression.

Treatment:

Drug: Daratumumab

Drug: Modakafusp Alfa

Phase 1 (Dose Escalation) Modakafusp Alfa 240 mg + Daratumumab

Experimental group

Description:

Modakafusp alfa 240 mg, infusion, IV, Q4W with daratumumab 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression.

Treatment:

Drug: Daratumumab

Drug: Modakafusp Alfa

Phase 2a Dose Finding: Modakafusp Alfa (DL1) + Daratumumab

Experimental group

Description:

Modakafusp alfa at dose level 1 (DL1) \[selected from Phase 1 Dose Escalation\] with daratumumab SC 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression.

Treatment:

Drug: Daratumumab

Drug: Modakafusp Alfa

Phase 2a Dose Finding: Modakafusp Alfa (DL2) + Daratumumab

Experimental group

Description:

Modakafusp alfa at dose level 2 (DL2) \[selected from Phase 1 Dose Escalation\] with daratumumab SC 1800 mg, SC, QW in Cycles 1 and 2, Q2W in Cycles 3 to 6, and Q4W thereafter in each 28-day treatment cycle until disease progression.

Treatment:

Drug: Daratumumab

Drug: Modakafusp Alfa