A Study to Investigate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of TAK-573 in Participants With Refractory Multiple Myeloma
- Conditions
- Relapsed/Refractory Multiple MyelomaTherapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 21.0Level: LLTClassification code 10028228Term: Multiple myelomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2021-006038-37-NO
- Lead Sponsor
- Takeda Development Center Americas, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 286
For Parts 1 and 2:
1. MM defined by the IMWG criteria with evidence of disease progression and:
a) Is in need of additional myeloma therapy as determined by the investigator.
b) Has previously received at least 3 lines of myeloma therapy (eg, containing an IMiD, a PI, an alkylating agent, and/or an anti-CD38 as single agents or in combination).
c) Is either refractory to, or intolerant of, at least 1 PI and at least 1 IMiD (see NOTE below).
For Part 3:
1. MM defined by the IMWG criteria with evidence of disease progression and:
a) Is in need of additional myeloma therapy as determined by the investigator.
b) Has previously received at least 3 lines of myeloma therapy.
c) Is refractory to at least 1 IMiD (ie, lenalidomide or pomalidomide [thalidomide excluded]), at least 1 PI (ie, bortezomib, ixazomib, or carfilzomib), and refractory to at least 1 anti-CD38 antibody (ie, daratumumab or isatuximab) and who have demonstrated disease progression during or after the last therapy (see NOTE below). Patients who were primary refractory to all previous therapies, meaning they never achieved at least a MR with any previous treatment line, are not eligible.
NOTE: Refractory is defined as ?25% reduction in M-protein or progression of disease during treatment or within 60 days after cessation of treatment.
A line of therapy is defined as 1 or more cycles of a planned treatment program. This may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. A new line of therapy starts when a planned course of therapy is modified to include other treatment agents (alone or in combination) as a result of disease progression, relapse, or toxicity. A new line of therapy also starts when a planned period of observation off therapy is interrupted by a need for additional treatment for the disease (Rajkumar et al. 2011).
2. Aged 18 years or older.
3. For patients in Parts 2 and 3 only: Measurable disease defined as one of the following:
a) Serum M-protein =500 mg/dL (=5 g/L).
b) Urine M-protein =200 mg/24 hours.
c) Serum free light chain (FLC) assay with involved FLC level =10 mg/dL (=100 mg/L) provided serum FLC ratio is abnormal.
4. During Part 1 only, patients not meeting the above criteria for measurable disease should, at least, have measurable bone marrow plasmacytosis (=10%) and/or plasmacytoma (=1 cm in diameter) detected by physical examination or imaging.
5. ECOG performance status of =2.
6. Patient has adequate organ function as determined by the following laboratory values. See Protocol for values.
7. Female patients who:
Are postmenopausal for at least 2 years before the screening visit, OR
Are surgically sterile, OR
If they are of childbearing potential:
– Agree to practice 1 highly effective method of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 7 days after the last dose of study
drug, OR
– Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the subject, from the time of signing the informed consent through 7 days after the last dose of study drug. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
– Agree not to donate an egg or eg
1. Patient has polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia or IgM myeloma, or lymphoplasmacytic lymphoma.
2. Patients who have received autologous SCT 60 days before first infusion of modakafusp alfa or patients who have received allogeneic SCT 6 months before first infusion.
3. Graft-versus-host disease that is active or requires ongoing systemic immunosuppression.
4. Part 1: Until the MTD/OBD is defined, patients who have received daratumumab (or other investigational anti-CD38 antibody) for at least 5 months (steady state) require a 90-day wash-out period before receiving modakafusp alfa. For patients who have received less than 5 months of daratumumab or who have received another anti-CD38 monoclonal antibody, the necessary wash-out period needs to be discussed and approved by the sponsor. Once the MTD/OBD has been confirmed, these patients can be enrolled in the trial (Parts 2 and 3).
Parts 2 and 3: No washout from daratumumab or isatuximab is required.
5. Patient has not recovered from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) to National Cancer Institute Common
Terminology Criteria for Adverse Events (NCI CTCAE) Grade =1 or baseline, except for sensory or motor neuropathy which should have recovered to Grade =2 or baseline.
6. Patient has received the final dose of any of the following treatments/procedures within the specified minimum intervals before the first dose of modakafusp alfa. See Protocol for values.
7. Patient 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.
8. Patient has a history of acute myocardial infarction within 5 months from enrollment or has electrocardiogram (ECG) abnormalities during screening that are deemed medically relevant by the investigator.
9. Patient has QT interval corrected by the Fridericia method (QTcF) >480 msec (Grade =2).
10. Patient has a concurrent illness that would preclude study conduct and assessment including, but not limited to, uncontrolled medical conditions, uncontrolled and active infection (considered opportunistic, life-threatening, or clinically significant), uncontrolled risk of bleeding, uncontrolled diabetes mellitus, pulmonary disease (including obstructive pulmonary disease, pulmonary fibrosis, and history of symptomatic bronchospasm), alcoholic liver disease, or primary biliary cirrhosis.
11. Patient has a chronic condition requiring the use of systemic corticosteroids >10 mg/day of
prednisone or equivalent.
12. Patient has clinical signs of central nervous system involvement of MM.
13. Female patients who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug if applicable.
14. Any serious medical or psychiatric illness that could, in the investigator’s opinion, potentially interfere with the completion of treatment according to this protocol.
15. Patient has a known history of human immunodeficiency virus.
16. Parts 1 and 2: Known chronic he
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method