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

Official Title

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

Summary:

The purpose of this study is to determine the safety and tolerability of TAK-981 in combination with rituximab in participants with r/r CD20+ NHL in Phase 1b, and to evaluate the efficacy of TAK-981 in combination with rituximab in r/r CD20+ NHL in Phase 2.

Trial Description

Primary Outcome:

• Phase 1b: Number of Participants With Overall and per Dose Level Treatment-emergent Adverse Events (TEAEs)
• Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) per Dose Level
• Phase 1b: Number of Participants With Greater Than or Equal to (>=) Grade 3 TEAEs
• Phase 1b: Number of Participants With one or More Serious Adverse Events (SAEs)
• Phase 1b: Number of Participants With Treatment Related Dose Modifications Including Dose Delays, Dose interruption and Dose Reductions, and Who Discontinued Due to TEAEs
• Phase 1b: Number of Participants With Clinically Significant Laboratory Values
• 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
• ORR According to Lugano Classification With Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) Modification
• Duration of Response (DOR)
• Progression-free Survival (PFS)
• Time to Response (TTR)
• 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 1b 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 determine the safety, tolerability and efficacy of TAK-981 in combination with rituximab in participants with r/r CD20+ NHL. The study will include a dose escalation phase (Phase 1b) and an open label study (Phase 2). The study will enroll approximately 90 participants, approximately 34 participants in Phase 1b and approximately 56 participants in Phase 2. The phase 1b will identify the maximum tolerated dose (MTD) and/or pharmacologically active dose (PAD). In the dose escalation phase, the starting dose of TAK-981 will be 3 mg, however, a starting dose of TAK-981 that is greater than (>) 3 mg may be considered if emerging preliminary safety experience from the ongoing TAK-981-1002 single agent study supports it. The starting dose level will be escalated based on available safety, PK and pharmacodynamic data, and after any early antitumour activity is observed. Participants in the Phase 2 will be enrolled once the Phase 1b of the study is completed, and MTD and/or PAD is determined. Participants in Phase 2 will be enrolled in 2 treatment arms: indolent non-Hodgkin lymphoma (iNHL) and aggressive non-Hodgkin lymphoma (aNHL). This multi-centre trial will be conducted in the United States and Canada. The overall time to participate in this study is approximately 36 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.

View this trial on ClinicalTrials.gov