TAK-169 for Relapsed or Refractory Multiple Myeloma (RRMM)

Trial Summary

Official Title

A Phase 1, Open-Label, Dose-Escalation, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TAK-169 in Patients With Relapsed or Refractory Multiple Myeloma

Status

Recruiting

Condition

Relapsed and/or Refractory Multiple Myeloma

About the Trial

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

The drug being tested in this study is called TAK-169. The study will evaluate the safety, tolerability, preliminary efficacy, PK, pharmacodynamic, and immunogenicity of TAK-169 monotherapy in participants with RRMM.

The study will be conducted in 2 phases: Dose Escalation Phase (Part 1) and an Expansion Phase (Part 2). The study will enroll approximately 81 to 102 participants (39 to 60 participants in Part 1 and approximately 54 participants in Part 2).

In the Dose Escalation Phase (Part 1), the starting dose level will be 50 microgram/kilogram (mcg/kg), once weekly. On the basis of investigator and sponsor review of available safety, PK, pharmacodynamic, and efficacy data from Cohort 1, the dose will be escalated in the subsequent cohorts to 100, 200, 335, 500, and 665 mcg/kg, once weekly. A separate dose escalation may also occur in which TAK-169 will be administered once every 2 weeks.

In the Expansion Phase (Part 2), the study will evaluate two types of RRMM cohorts: Daratumumab-relapsed or Refractory (RR) Cohorts (once weekly and once every 2 weeks TAK-169 administration) and an Anti-CD38 Therapy Naive Cohort (once weekly TAK-169 administration). The starting dose for each expansion cohort will be the MTD/RP2D (once weekly and once every 2 weeks) determined in Part 1 after review of the available safety, efficacy, PK, and pharmacodynamic data from the dose escalation phase of the study.

This multi-center trial will be conducted in the United States. The overall duration of the study is 34 months. Participants will be followed up for 30 days after the last dose of study drug for a follow-up assessment.

Detailed Info

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of TAK-169, establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), and to provide a preliminary evaluation of the clinical activity of TAK-169 monotherapy in participants with RRMM.

Study Phase

Phase 1

Estimated Enrollment

102

Study Type

Interventional

Interventions

Drug: TAK-169

Sponsor

Millennium Pharmaceuticals, Inc.

Eligibility

Inclusion Criteria Exclusion Criteria

Gender

Male & Female

Age

18 Years and older

Inclusion Criteria Part 1

With a confirmed diagnosis of MM.
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.
Should meet all of the following criteria for prior therapy:
- Should be refractory to at least one proteasome inhibitor (PI), at least one immunomodulatory drug (IMiD), and at least 1 steroid.
- Should either have received >=3 prior lines of therapy or should 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.
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.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
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
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

With a confirmed diagnosis of MM.
Should meet all of the following criteria for prior therapy:
- Should be refractory or intolerant to at least 1 PI and at least 1 IMiD.
- Should either have received >=3 prior lines of therapy or should 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.
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
ECOG performance status score of 0 or 1.
With normal QTcF on screening ECG, defined as QTcF of <=450 ms in males or <=470 ms in females
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).

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.
With sensory or motor neuropathy of NCI CTCAE Grade >=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
Have received an allogeneic stem cell transplant or organ transplantation.
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.
With clinical signs of central nervous system (CNS) involvement of MM.
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).
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.
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).
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
With a chronic condition requiring the use of systemic corticosteroids at a dose of >10 milligram per day (mg/day) of prednisone or equivalent.

Location

The following cities have clinical trial sites. Please check back often as locations will be updated.

Mayo Clinic - Jacksonville
Jacksonville, Florida 32224
United States
Recruiting

Mayo Clinic - Rochester
Rochester, Minnesota 55905
United States
Recruiting

Enrollment

For more information on enrollment in our current clinical trials, please visit clinicaltrials.gov for location information.

Visit clinicaltrials.gov

About Relapsed or Refractory Multiple Myeloma (RRMM)

Multiple myeloma (MM) is a cancer of plasma cells. Plasma cells are found mainly in the bone marrow and they make the antibodies (also known as immunoglobulins) that help the body fight and kill germs. MM is a cancer that develops when plasma cells grow out of control.

Relapsed (or recurrent) multiple myeloma is the term for when cancer returns after treatment or after a period of remission. Most multiple myeloma patients will relapse at some point as this cancer is still incurable. Refractory multiple myeloma refers to when the cancer does not respond to therapy. In some cases, the cancer will respond to initial treatment, but not to treatments following relapse.

Frequently Asked Questions

What is a clinical trial?

A Clinical Trial is a type of research study that examines how well a potential therapy works in humans.

Why is this trial being done?

The purpose of this study is to evaluate the safety and tolerability of TAK-169, establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), and to provide a preliminary evaluation of the clinical activity of TAK-169 monotherapy in participants with RRMM.