The drug being tested in this study is called TAK-981. TAK-981 in combination with an
anti-CD38 monoclonal antibody (mAbs) 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 participants; 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 with fixed doses as follows:
- Phase 1b, Part 1 - Dose Escalation: Arm A - TAK-981 Twice Weekly (BIW) + Mezagitamab
- Phase 1b, Part 1 - Dose Escalation: Arm B - TAK-981 Weekly (QW) + Mezagitamab
- Phase 1b, 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 2 years. 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
drug.
Inclusion Criteria:
1. Participants must have RRMM with measurable disease:
a) Has measurable disease defined as one of the following:
- Serum M-protein â¥0.5 g/dL (â¥5 g/L).
- Urine M-protein â¥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 â¥10 mg/dL (â¥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 immunomodulatory drug ( 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.
5.Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale.
6.Have recovered to Grade 1 or baseline from all toxicity associated with previous therapy
or have the toxicity established as sequela.
Exclusion Criteria:
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 1b 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
infection.
13. Systemic infection requiring systemic antibiotic therapy.
14. Active or history pneumonitis.
15. Receipt of any live vaccine (eg, varicella, pneumococcus) within 4 weeks of initiation
of study drug.
16. Receiving strong or moderate Cytochrome P450 (CYP) 3A4/5 inhibitors or inducers.
17. History of unstable cardiac comorbidities in the following 6 months.
