The drug being tested in this study is called TAK-981. TAK-981 in combination with an
anti-CD38 monoclonal antibody is being tested to treat people who have RRMM. The study will
include a dose escalation phase and a dose expansion phase.
The study will enroll approximately 81 patients, approximately 30 participants in the dose
escalation phase (Part 1) approximately 15 participants in (Part 2) and up to 36 participants
in dose expansion phase (Part 2). Participants will receive escalating doses of TAK-981 in
combination of fixed doses as follows:
- Phase 1, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + Mezagitamab
- Phase 1, Part 1 - Dose Escalation: Arm B - TAK-981 Weekly (QW) + Mezagitamab
- Phase 1, Part 2 - Dose Escalation: TAK-981 + Daratumumab and Hyaluronidase-fihj
Once RP2D is determined in Phase 1, participants with RRMM will be enrolled in Phase 2.
• Phase 2 - Dose Expansion: TAK-981 + Daratumumab and Hyaluronidase-fihj or Mezagitamab
This multi-center trial will be conducted in North America. The overall time to participate
in this study is 48 months. Participants will make multiple visits to the clinic, and
progression-free survival follow-up for maximum up to 12 months after last dose of study
1. Participants must have RRMM with measurable disease:
1. Has measurable disease defined as one of the following:
- Serum M-protein ≥0.5 g/dL (≥5 g/L).
- Urine M-protein ≥200 mg/24 hours.
- In participants without measurable M-protein in serum protein
electrophoresis (SPEP) or urine protein electrophoresis (UPEP), a serum free
light chain (FLC) assay result with involved FLC level ≥10 mg/dL (≥100
mg/L), provided serum FLC ratio is abnormal.
2. Has undergone stem cell transplant or is considered transplant ineligible.
3. Has failed at least 3 prior lines of anti-myeloma treatments and is either
refractory, or intolerant to at least 1 IMiD (ie, lenalidomide or pomalidomide
[thalidomide excluded]), at least 1 proteasome inhibitor (ie, bortezomib,
ixazomib or carfilzomib), and refractory to at least 1 anti-CD38 antibody and who
have demonstrated disease progression with the last therapy.
2. Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG)
3. Have recovered to Grade 1 or baseline from all toxicity associated with previous
therapy or have the toxicity established as sequela.
1. Received treatment with systemic anticancer treatments within 14 days before the first
dose of study drug.
2. Current participation in another interventional study, including other clinical trials
with investigational agents (including investigational vaccines or investigational
medical device for disease under study).
within 4 weeks of the first dose of TAK-981 and throughout the duration of this trial.
3. Prior radiation therapy within 14 days of the first dose of TAK-981.
4. Major surgery within 4 weeks before C1D1. participants should be fully recovered from
any surgically related complications.
5. Plasmapheresis within 28 days of randomization.
6. Diagnosis of primary amyloidosis, Waldenström's disease, monoclonal gammopathy of
undetermined significance or smoldering multiple myeloma (SMM), plasma cell leukemia
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
skin changes), myelodysplastic syndrome, or myeloproliferative syndrome.
7. With disease where the only measurable parameter is plasmacytoma.
8. Second malignancy within the previous 3 years, except treated basal cell or localized
squamous skin carcinomas, localized prostate cancer, cervical carcinoma in situ,
resected colorectal adenomatous polyps, breast cancer in situ, or other malignancy for
which the participant is not on active anticancer therapy.
9. Prior treatment with more than 1 anti-CD38 antibody.
10. Requires the use of drugs known to prolong the corrected QT interval (QTc) (during
Phase 1 only).
11. History of QT interval with Fridericia's correction (QTcF) >480 ms.
12. History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C
13. Systemic infection requiring systemic antibiotic therapy.
14. Active or history pneumonitis.
15. Receipt of any live vaccine within 4 weeks of initiation of study drug.
16. Receiving strong or moderate Cytochrome P450 (CYP3A4/5) inhibitors or inducers.
17. History of unstable cardiac comorbidities in the following 6 months.