A Study of TAK-981 in Combination With Rituximab in Participants With Relapsed/Refractory (r/r) CD20-positive (CD20+) Non-Hodgkin Lymphoma (NHL)

Titre officiel

Phase 1/2 Study of TAK-981 in Combination With Rituximab in Patients With Relapsed/Refractory CD20-Positive Non-Hodgkin Lymphoma

Sommaire:

The purpose of this study is to determine the safety, tolerability and to establish the recommended Phase 2 dose (RP2D) of TAK-981 in combination with rituximab in participants with r/r CD20+ NHL in Phase 1, and to evaluate the efficacy of TAK-981 in combination with rituximab in select r/r CD20+ NHL indications in Phase 2.

Description de l'essai

Primary Outcome:

  • Phase 1: Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)
  • Phase 1: Number of Participants with Grade 3 or Higher TEAEs
  • Phase 1: Duration of TEAEs
  • Phase 1: Number of Participants With Clinically Significant Laboratory Values
  • Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs) per Dose Level
  • Phase 2: Overall Response Rate (ORR) Assessed by Investigator According to Lugano Classification for Lymphomas
Secondary Outcome:
  • Cmax: Maximum Observed Plasma Concentration for TAK-981
  • Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-981
  • AUCt: Area Under the Plasma Concentration-time Curve from Time 0 to Time t Over the Dosing Interval for TAK-981
  • AUC∞: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-981
  • t1/2z: Terminal Disposition Phase Half-life for TAK-981
  • CL: Total Clearance After Intravenous Administration for TAK-981
  • Vss: Volume of Distribution at Steady State After Intravenous Administration for TAK-981
  • Phase 1: Overall Response Rate (ORR) Assessed by Investigator According to Lugano Classification for Lymphomas
  • Disease Control Rate (DCR) Assessed by Investigator According to Lugano Classification for Lymphomas
  • Duration of Response (DOR) Assessed by Investigator According to Lugano Classification for Lymphoma
  • Progression-Free Survival (PFS) Assessed by Investigator According to Lugano Classification for Lymphoma
  • Time to Progression (TTP) Assessed by Investigator According to Lugano Classification for Lymphoma
  • Number of Participants With TAK-981-Small Ubiquitin-like Modifier (TAK-981-SUMO) Adduct Formation and SUMO Pathway Inhibition in Skin and Blood During Phase 1 and in Skin, Blood and Tumour Tissues During Phase 2
The drug being tested in this study is called TAK-981 in combination with rituximab. The study will include a dose escalation phase (Phase 1) and an expansion phase in select NHL indications (Phase 2). The study will enroll approximately 130 participants, approximately 35 participants in Phase 1 and approximately 95 participants in Phase 2. The participants with indolent or aggressive relapsed or refractory (r/r) NHL in Phase 1 will identify the maximum tolerated dose (MTD) and/or pharmacologically active dose (PAD). PAD can be defined retrospectively once MTD is reached and it can below MTD or coincide with it. In the dose escalation phase, the starting dose of TAK-981 will be 10 mg. The RP2D will be determined based on the available safety, preliminary pharmacokinetic (PK), pharmacodynamic information data, and after any early antitumour activity observed along with the statistical inference from the Bayesian Logistic Regression Modeling (BLRM). Participants in the Phase 2 will be enrolled once the Phase 1 of the study is completed, and MTD and/or PAD is determined. Phase 2 will explore the efficacy and safety of TAK-981 in combination with rituximab in participants with select r/r NHL types and indications. Participants in Phase 2 will be enrolled in one of the three treatment arms based on Cohorts:
  • Cohort A: r/r DLBCL Progressed to CAR T-cell therapy
  • Cohort B: r/r DLBCL with no CAR T-cell Prior Therapy
  • Cohort C: r/r FL Progressed to Systemic Therapies This multi-centre trial will be conducted in the United States and Canada. The overall time to participate in this study is approximately 48 months. Participants will make multiple visits to the clinic, and will attend the end of treatment (EOT) visit 30 days after receiving their last dose of drug or before the start of subsequent systemic anticancer therapy, whichever occurs first for a follow-up assessment.

Voir cet essai sur ClinicalTrials.gov

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