A Study of Modakafusp Alfa on Adult Participants With Relapsed/Refractory Multiple Myeloma

Official Title

A Phase 1/2 Open-label Study to Investigate the Safety and Tolerability, Efficacy, Pharmacokinetics, and Immunogenicity of Modakafusp Alfa (TAK-573) as a Single Agent in Patients With Relapsed Refractory Multiple Myeloma

Summary:

The main aims of this 3-part study are as follows:

Part 1: To determine any side effects from modakafusp alfa single treatment and how often they occur. The dose of modakafusp alfa will be increased a little at a time until the highest dose that does not cause harmful side effects is found.

Part 2: To assess clinical activity of one or more dosing schedules of modakafusp alfa alone in participants with relapsed/refractory multiple myeloma. Dexamethasone standard dose will be administered with one or more selected dose of modakafusp alfa in selected group of participants.

Part 3: To find the optimal dose with the more favorable risk-benefit profile of modakafusp alfa.

Participants will receive modakafusp alfa at one of two doses which will be given through a vein.

Trial Description

Primary Outcome:

  • Part 1: Percentage of Participants Reporting one or More Treatment Emergent Adverse Events (TEAEs)
  • Part 1: Percentage of Participants With Dose-limiting Toxicities (DLTs)
  • Part 1: Percentage of Participants Reporting one or More Grade 3 TEAEs
  • Part 1: Percentage of Participants Reporting one or More Serious Adverse Events (SAEs)
  • Part 1: Percentage of Participants Who Discontinue the Treatment Because of TEAE
  • Part 1: Percentage of Participants With Dose Modifications: Dose Delay
  • Part 1: Percentage of Participants With Dose Modifications: Dose Interruptions
  • Part 1: Percentage of Participants With Dose Modifications: Dose Reductions
  • Part 1: Percentage of Participants With Clinically Significant Laboratory Values
  • Part 1: Percentage of Participants With Clinically Significant Vital Signs Measurements
  • Part 2: Overall Response Rate (ORR)
  • Part 3: Overall Response Rate (ORR) Assessed by Independent Review Committee (IRC)
Secondary Outcome:
  • Part 1 and 2: Percentage of Participants With Dose-limiting Toxicities (DLTs)- Like Events
  • Part 1: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa
  • Part 1: Tmax: Time to Reach the Cmax for Modakafusp alfa
  • Part 1: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa
  • Part 1: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Modakafusp alfa
  • Part 1: λz: Terminal Disposition Rate Constant for Modakafusp alfa
  • Part 1: T1/2: Terminal Elimination Half-life for Modakafusp alfa
  • Part 1: CL: Clearance for Modakafusp alfa
  • Part 1: Vss: Volume of Distribution at Steady State for Modakafusp alfa
  • Parts 1, 2 and 3: Percentage of Participants with Positive Anti-drug Antibodies (ADA)
  • Part 1: Objective Response Rate (ORR)
  • Parts 1 and 2: Clinical Benefit Rate (CBR)
  • Parts 1 and 2: Disease Control Rate (DCR)
  • Parts 1, 2 and 3: Duration of Response (DOR)
  • Parts 1 and 2: Time to Response
  • Parts 1, 2 and 3: Progression Free Survival (PFS)
  • Parts 2 and 3: Overall Survival (OS)
  • Part 2: Cmax: Maximum Observed Serum Concentration for Modakafusp alfa
  • Part 2: AUC∞: Area Under the Serum Concentration-time Curve from Time 0 to Infinity for Modakafusp alfa
  • Part 2: AUClast: Area Under the Serum Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Modakafusp alfa
  • Part 2: λz: Terminal Disposition Rate Constant for Modakafusp alfa
  • Part 2: Tmax: Time to Reach the Cmax for Modakafusp alfa
  • Part 2: CL: Clearance for Modakafusp alfa
  • Part 2: Vss: Volume of Distribution at Steady State for Modakafusp alfa
  • Part 2: T1/2z: Terminal Elimination Half-life for Modakafusp alfa
  • Part 3: Objective Response Rate (ORR) by Investigator Assessment
  • Part 3: Clinical Benefit Rate (CBR) by IRC and Investigator assessment
  • Part 3: Duration of Clinical Benefit
  • Part 3: Disease Control Rate (DCR) by IRC and Investigator Assessment
  • Part 3: Duration of Disease Control
  • Part 3: Time to Progression (TTP) by IRC and Investigator Assessment
  • Part 3: Rate of Minimal Residual Disease (MRD) Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR
  • Part 3:Duration of MRD Negativity Status at a Sensitivity of 10^-5 in Participants Achieving CR
  • Part 3: Percentage of Participants With Adverse Events (AEs)
  • Part 3: Percentage of Participants With Serious Adverse Events (SAEs)
  • Part 3: Percentage of Participants With Clinically Significant Laboratory Values
  • Part 3: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Status
  • Part 3: Health Care Utilization: Length of Hospital Stays
  • Part 3: Percentage of Participants With Neutralizing Antibodies (NAb)
  • Part 3: Health Care Utilization: Number of Participants With at Least One Medical Encounter
  • Part 3: Patient-reported Outcome (PRO): Instrument European Organisation for Research and Treatment of Cancer QLQ Questionnaire Multiple Myeloma Module (EORTC QLQ-MY20)

The drug being tested in this study, and which will be given through a vein, is called modakafusp alfa (TAK-573 ) as single agent or in combination with dexamethasone. The study will determine the safety, tolerability, and efficacy of modakafusp alfa as single agent and in combination with dexamethasone in participants with relapsed/refractory multiple myeloma (RRMM). The study consists of 3 Parts:

Part 1: Dose Escalation, Part 2: Dose Expansion, Part 3: Dose Extension

The study will enroll approximately 65 participants in Part 1, 35 in Part 2, and 236 in Part 3. Participants will be assigned to one of the following treatment groups in Parts 1 and 2 of the study. Participants will be randomly assigned in Part 3 of the study as given below:

  • Part 1 (Dose Escalation) Schedule A: Modakafusp alfa 0.001 Up to 14 mg/kg
  • Part 1 (Dose Escalation) Schedule B: Modakafusp alfa TBD
  • Part 1 (Dose Escalation) Schedule C: Modakafusp alfa TBD
  • Part 1 (Dose Escalation) Schedule D: Modakafusp alfa TBD
  • Part 2 (Dose Expansion): Modakafusp alfa TBD + Dexamethasone 40 mg
  • Part 3 (Dose Extension): Modakafusp alfa 120 mg
  • Part 3 (Dose Extension): Modakafusp alfa 240 mg

The Part 1 (Dose Escalation) portion of the study will follow a 3+3 dose escalation design to evaluate once-weekly up to 4 different schedules of administration of modakafusp alfa starting at 0.001 mg/kg for dose limiting toxicity (DLT) evaluation and to determine the maximum tolerated dose (MTD) or an optimal biological dose (OBD) for assessments in Part 2.

The Part 2 (Dose Expansion) will further assess the safety profile of modakafusp alfa and its efficacy at MTD or OBD.

For Part 3 (Dose Extension) participants will be randomized 1:1 to receive single-agent modakafusp alfa 120 mg or 240 mg Q4W.

Parts 1 and 2 will be conducted at multiple centers in the United States. Part 3 will be conducted worldwide. The maximum treatment duration in this study is up to 12 months (Parts 1 and 2) or until disease progression (Part 3) and overall time to participate in the study is approximately up to 90 months. Participants with clinical benefit may continue treatment after sponsor approval.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society