A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK), and Efficacy of TAK-169 in Participants With Relapsed or Refractory Multiple Myeloma

Overview

Multiple Myeloma is a type of blood cancer in cells made in the bone marrow. Relapsed means the previous cancer treatment worked for a while but stopped working, over time. Refractory means people did not respond to previous cancer treatment. TAK-169 is a medicine that binds to the surface of multiple myeloma cells called CD38 cells. It delivers a dose of chemotherapy to the CD38 cells.

This study is in 2 parts.

The main aims of Part 1 of the study are to check how much TAK-169 a person can receive without getting side effects from it, and to work out the best dose of TAK-169 to give people to treat their cancer. The main aim of Part 2 of the study is to learn if the condition of people with multiple myeloma improves after treatment with TAK-169. Another aim is to check for side effects from TAK-169.

In Part 1, at the first visit, the study doctor will check who can take part. Participants who can take part will receive TAK-169 slowly through the vein (infusion). This will happen once a week during a 28-day cycle. Different small groups of participants will receive lower to higher doses of TAK-169. The study doctors will check for side effects after each dose of TAK 169. In this way, researchers can work out the best dose of TAK-169 to give participants in Part 2 of the study. Each participant will stay in the clinic for at least 24 hours after they have received their first infusion of TAK-169.

Once the best dose has been worked out, different small groups of participants will receive lower to higher doses of TAK-169 every 2 weeks, starting at the best dose.

In Part 2, at the first visit, the study doctor will check who can take part, as only some participants with multiple myeloma can take part.

Participants who previously did not respond to daratumumab or it worked for a while but stopped working, over time will have 1 of 2 treatments.

  • Some will receive TAK-169 once a week.
  • Others will receive TAK-169 every 2 weeks.

Participants who have never previously received other medicines that bind to the multiple myeloma CD38 cells can also take part. They will receive TAK-169 once a week.

All participants in Part 2 will receive the best dose of TAK-169 worked out in Part 1.

In both parts of the study, participants can receive TAK-169 for up to 1 year. They could receive TAK-169 for longer than 1 year if their multiple myeloma continues to improve or remains stable during treatment. After treatment has finished, participants will visit the clinic for a check-up every 12 weeks.

SparkCures ID 1074
Trial Phase Phase 1
Enrollment 102 Patients
Treatments
Tags
  • CD38
  • Engineered Toxin Body (EBT)
Trial Sponsors
  • Takeda Oncology
NCT Identifier

NCT04017130
ACCEPTING

This trial is currently open and accepting patients.

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

Inclusion Criteria:

Inclusion Criteria Part 1

  1. With a confirmed diagnosis of MM.
  2. With RRMM who have failed treatment with, are intolerant to, or are not candidates for available therapies that are known to confer clinical benefit in this participant population.
  3. Must meet all of the following criteria for prior therapy:
    • Must be refractory to at least one proteasome inhibitor (PI), at least one immunomodulatory drug (IMiD), and at least 1 steroid.
    • Must either have received >=3 prior lines of therapy or must have received at least two prior lines of therapy if one of those lines included a combination of PI and IMiD.
    • Prior treatment with an anti-CD38 therapy (including daratumumab) is permitted.
  4. With measurable disease, defined as at least 1 of the following:
      • Serum M-protein >=500 mg/dL (>=5 g/L) on serum protein electrophoresis (SPEP).
      • Urine M-protein >=200 mg/24 h on urine protein electrophoresis (UPEP).
      • Serum FLC assay result with an involved FLC level >=10 mg/dL (>=100 milligram per liter [mg/L]), provided the serum FLC ratio is abnormal.
  5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  6. With normal QT interval corrected by the Fridericia method (QTcF) on screening electrocardiogram (ECG), defined as QTcF of <=450 millisecond (ms) in males or <=470 ms in females
  7. Must meet the following clinical laboratory criteria at study entry:
    • Total bilirubin <=1.5*the upper limit of the normal range (ULN), except for participant with Gilbert's syndrome, in whom the direct bilirubin must be <2.0*ULN.
    • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be <=2.5*ULN.
    • Estimated glomerular filtration rate (eGFR) >=30 milliliters per minute (mL/min/1.73 square meter [m^2], using the modification of diet in renal disease (MDRD) equation.
    • Absolute neutrophil count (ANC) >=1000 per cubic millimeter (/mm^3) (>=1.0*10^ 9 per liter [/L]); a count of >=750/mm^3 (>=0.75*10^ 9/L) may be acceptable for participants with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Platelet count >=75,000/ mm^3 (>=75*10^ 9/L); a value of >=50,000/ mm^3 (>=50*10^ 9/L) may be acceptable for participants with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Hemoglobin >=7.5 g/dL (it is not permissible to transfuse a participant to reach this level).

Inclusion Criteria Part 2

  1. With a confirmed diagnosis of MM.
  2. Must meet all of the following criteria for prior therapy:
    • Must be refractory or intolerant to at least 1 PI and at least 1 IMiD.
    • Must either have received >=3 prior lines of therapy or must have received at least 2 prior lines of therapy if 1 of those lines included a combination of PI and IMiD.
    • Prior treatment with an anti-CD38 therapy (including daratumumab) is permitted, except for participants enrolled into the anti-CD38-therapy naïve expansion cohort.
    • Daratumumab-RR cohorts (once weekly and once every two weeks TAK-169 dosing): Participant must be RR to daratumumab at any time during treatment. Of note, participant's RR to other anti-CD38 therapies are excluded.
    • Anti-CD38 Therapy Naïve cohort (once weekly dosing): Participants must not have received any prior anti-CD38 therapy.
  3. With measurable disease, defined as at least 1 of the following:
      • Serum M-protein >=500 mg/dL (>=5 g/L) on SPEP.
      • Urine M-protein >=200 mg/24 hours on UPEP.
      • Serum FLC assay result with an involved FLC level >=10 mg/d (>=100 mg/L), provided the serum FLC ratio is abnormal
  4. ECOG performance status score of 0 or 1.
  5. With normal QTcF on screening ECG, defined as QTcF of <=450 ms in males or <=470 ms in females
  6. Must meet the following clinical laboratory criteria at study entry:
    • Total bilirubin <=1.5*the ULN, except for participant with Gilbert's syndrome, in whom the direct bilirubin must be <2.0*ULN.
    • Serum ALT and ASTmust be <=2.5*ULN.
    • eGFR >=30 mL/min/1.73 m^2, using the MDRD equation.
    • ANC >=1000 mm^3 (>=1.0*10^ 9 /L); a count of >=750/mm^3 (>=0.75*10^ 9/L) may be acceptable for participant with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Platelet count >=75,000/ mm^3 (>=75*10^ 9/L); a value of >=50,000/ mm^3 (>=50*10^ 9/L) may be acceptable for participants with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Hemoglobin >=7.5 g/dL (it is not permissible to transfuse a participant to reach this level).

Exclusion Criteria:

 

  1. With polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, or Immunoglobulin M (IgM) myeloma.
  2. With sensory or motor neuropathy of NCI CTCAE Grade >=3.
  3. Have received a final dose of any of the following treatments/procedures within the following minimum interval before the first dose of TAK-169:
    • Myeloma-specific therapy, including PIs and IMiDs-14 days
    • Anti-CD38 (a) therapy (Once the MTD/RP2D has been established, the washout period may be adjusted in the expansion phase (Part 2) of the study for participants who have received anti-CD38 therapy )-90 days
    • Corticosteroid therapy for myeloma- 7 days
    • Radiation therapy for localized bone lesions- 14 days
    • Major surgery-30 days
    • Autologous stem cell transplant- 90 days
    • Investigational therapy- 30 days
  4. Have received an allogeneic stem cell transplant or organ transplantation.
  5. Have not recovered, to NCI CTCAE V5 Grade <=1 or baseline, from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia.
  6. With clinical signs of central nervous system (CNS) involvement of MM.
  7. With known or suspected light chain amyloidosis of any organ (the presence of amyloid on the bone marrow biopsy without other evidence of amyloidosis is acceptable).
  8. With congestive heart failure (New York Heart Association) class >=II or left ventricular ejection fraction (LVEF <40%, cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris or myocardial infarction within the past 6 months, clinically significant arrhythmia requiring therapy including anticoagulants, or clinically significant uncontrolled hypertension. Participants are also excluded if cardiac MRI demonstrates evidence of infiltrative disease of the myocardium, such as amyloid cardiomyopathy.
  9. With chronic or active infection requiring systemic therapy, as well as a history of symptomatic viral infection that has not been fully cured (example, human immunodeficiency viruses (HIV) or viral hepatitis B or C).
  10. With a history of systemic inflammatory response syndrome (SIRS)/ cytokine release syndrome (CRS) reactions following infusion with any monoclonal antibodies or Chimeric Antigen Receptor (CAR) T-cell therapy
  11. With a chronic condition requiring the use of systemic corticosteroids at a dose of >10 milligram per day (mg/day) of prednisone or equivalent.

The following criteria is provided for health care professionals.

Inclusion Criteria:

Inclusion Criteria Part 1

  1. With a confirmed diagnosis of MM.
  2. With RRMM who have failed treatment with, are intolerant to, or are not candidates for available therapies that are known to confer clinical benefit in this participant population.
  3. Must meet all of the following criteria for prior therapy:
    • Must be refractory to at least one proteasome inhibitor (PI), at least one immunomodulatory drug (IMiD), and at least 1 steroid.
    • Must either have received >=3 prior lines of therapy or must have received at least two prior lines of therapy if one of those lines included a combination of PI and IMiD.
    • Prior treatment with an anti-CD38 therapy (including daratumumab) is permitted.
  4. With measurable disease, defined as at least 1 of the following:
      • Serum M-protein >=500 mg/dL (>=5 g/L) on serum protein electrophoresis (SPEP).
      • Urine M-protein >=200 mg/24 h on urine protein electrophoresis (UPEP).
      • Serum FLC assay result with an involved FLC level >=10 mg/dL (>=100 milligram per liter [mg/L]), provided the serum FLC ratio is abnormal.
  5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  6. With normal QT interval corrected by the Fridericia method (QTcF) on screening electrocardiogram (ECG), defined as QTcF of <=450 millisecond (ms) in males or <=470 ms in females
  7. Must meet the following clinical laboratory criteria at study entry:
    • Total bilirubin <=1.5*the upper limit of the normal range (ULN), except for participant with Gilbert's syndrome, in whom the direct bilirubin must be <2.0*ULN.
    • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be <=2.5*ULN.
    • Estimated glomerular filtration rate (eGFR) >=30 milliliters per minute (mL/min/1.73 square meter [m^2], using the modification of diet in renal disease (MDRD) equation.
    • Absolute neutrophil count (ANC) >=1000 per cubic millimeter (/mm^3) (>=1.0*10^ 9 per liter [/L]); a count of >=750/mm^3 (>=0.75*10^ 9/L) may be acceptable for participants with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Platelet count >=75,000/ mm^3 (>=75*10^ 9/L); a value of >=50,000/ mm^3 (>=50*10^ 9/L) may be acceptable for participants with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Hemoglobin >=7.5 g/dL (it is not permissible to transfuse a participant to reach this level).

Inclusion Criteria Part 2

  1. With a confirmed diagnosis of MM.
  2. Must meet all of the following criteria for prior therapy:
    • Must be refractory or intolerant to at least 1 PI and at least 1 IMiD.
    • Must either have received >=3 prior lines of therapy or must have received at least 2 prior lines of therapy if 1 of those lines included a combination of PI and IMiD.
    • Prior treatment with an anti-CD38 therapy (including daratumumab) is permitted, except for participants enrolled into the anti-CD38-therapy naïve expansion cohort.
    • Daratumumab-RR cohorts (once weekly and once every two weeks TAK-169 dosing): Participant must be RR to daratumumab at any time during treatment. Of note, participant's RR to other anti-CD38 therapies are excluded.
    • Anti-CD38 Therapy Naïve cohort (once weekly dosing): Participants must not have received any prior anti-CD38 therapy.
  3. With measurable disease, defined as at least 1 of the following:
      • Serum M-protein >=500 mg/dL (>=5 g/L) on SPEP.
      • Urine M-protein >=200 mg/24 hours on UPEP.
      • Serum FLC assay result with an involved FLC level >=10 mg/d (>=100 mg/L), provided the serum FLC ratio is abnormal
  4. ECOG performance status score of 0 or 1.
  5. With normal QTcF on screening ECG, defined as QTcF of <=450 ms in males or <=470 ms in females
  6. Must meet the following clinical laboratory criteria at study entry:
    • Total bilirubin <=1.5*the ULN, except for participant with Gilbert's syndrome, in whom the direct bilirubin must be <2.0*ULN.
    • Serum ALT and ASTmust be <=2.5*ULN.
    • eGFR >=30 mL/min/1.73 m^2, using the MDRD equation.
    • ANC >=1000 mm^3 (>=1.0*10^ 9 /L); a count of >=750/mm^3 (>=0.75*10^ 9/L) may be acceptable for participant with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Platelet count >=75,000/ mm^3 (>=75*10^ 9/L); a value of >=50,000/ mm^3 (>=50*10^ 9/L) may be acceptable for participants with >50% of plasma cells in bone marrow, after discussion with the sponsor.
    • Hemoglobin >=7.5 g/dL (it is not permissible to transfuse a participant to reach this level).

Exclusion Criteria:

 

  1. With polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome, monoclonal gammopathy of unknown significance, smoldering myeloma, solitary plasmacytoma, amyloidosis, Waldenström macroglobulinemia, or Immunoglobulin M (IgM) myeloma.
  2. With sensory or motor neuropathy of NCI CTCAE Grade >=3.
  3. Have received a final dose of any of the following treatments/procedures within the following minimum interval before the first dose of TAK-169:
    • Myeloma-specific therapy, including PIs and IMiDs-14 days
    • Anti-CD38 (a) therapy (Once the MTD/RP2D has been established, the washout period may be adjusted in the expansion phase (Part 2) of the study for participants who have received anti-CD38 therapy )-90 days
    • Corticosteroid therapy for myeloma- 7 days
    • Radiation therapy for localized bone lesions- 14 days
    • Major surgery-30 days
    • Autologous stem cell transplant- 90 days
    • Investigational therapy- 30 days
  4. Have received an allogeneic stem cell transplant or organ transplantation.
  5. Have not recovered, to NCI CTCAE V5 Grade <=1 or baseline, from adverse reactions to prior myeloma treatment or procedures (chemotherapy, immunotherapy, radiation therapy) excluding alopecia.
  6. With clinical signs of central nervous system (CNS) involvement of MM.
  7. With known or suspected light chain amyloidosis of any organ (the presence of amyloid on the bone marrow biopsy without other evidence of amyloidosis is acceptable).
  8. With congestive heart failure (New York Heart Association) class >=II or left ventricular ejection fraction (LVEF <40%, cardiac myopathy, active ischemia, or any other uncontrolled cardiac condition such as angina pectoris or myocardial infarction within the past 6 months, clinically significant arrhythmia requiring therapy including anticoagulants, or clinically significant uncontrolled hypertension. Participants are also excluded if cardiac MRI demonstrates evidence of infiltrative disease of the myocardium, such as amyloid cardiomyopathy.
  9. With chronic or active infection requiring systemic therapy, as well as a history of symptomatic viral infection that has not been fully cured (example, human immunodeficiency viruses (HIV) or viral hepatitis B or C).
  10. With a history of systemic inflammatory response syndrome (SIRS)/ cytokine release syndrome (CRS) reactions following infusion with any monoclonal antibodies or Chimeric Antigen Receptor (CAR) T-cell therapy
  11. With a chronic condition requiring the use of systemic corticosteroids at a dose of >10 milligram per day (mg/day) of prednisone or equivalent.
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US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Mayo Clinic (Jacksonville)

Jacksonville, FL

Mayo Clinic (Rochester)

Rochester, MN

Florida
Mayo Clinic (Jacksonville)

Jacksonville, FL

  • Recruiting
Minnesota
Mayo Clinic (Rochester)

Rochester, MN

  • Recruiting

Resources

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