Lymphoma, Non-Hodgkin
Conditions
Keywords
Drug Therapy
Brief summary
The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) for TAK-659 when administered in combination with NKTR-214.
Detailed description
The drugs that are being tested in this study are TAK-659 and NKTR-214. TAK-659 in combination with NKTR-214 is being tested for participants with advanced B-cell NHL, including DLBCL, FL, MZL, or MCL, after 2 prior lines of therapy. The study will determine the MTD or the RP2D of TAK-659 when administered with NKTR-214. The study will enroll approximately 40 participants, approximately 18 to 24 participants in a dose escalation phase, and approximately 12 participants will be added after determination of MTD/RP2D in the safety expansion phase. This study consists of 2 phases: a dose escalation phase and a safety expansion phase. TAK-659 and NKTR-214 doses will be escalated according to a modified 3+3 dose escalation schema. TAK-659 60 milligram (mg) + NKTR-214 0.003 milligram per kilogram (mg/kg) is the starting dose. Participants could also receive 80 mg once daily (QD) TAK-659 during dose escalation and 0.003mg/kg or 0.006mg/kg of NKTR-214. Lower doses (example 40 mg) and/or alternative regimens (including intermittent dosing) or schedules of TAK-659 are permissible following discussion between sponsor and investigators. In dose escalation phase, dose levels will be escalated based on available safety and tolerability data to determine the MTD or RP2D. Dose for safety expansion phase will be based on available safety, pharmacodynamics, and preliminary efficacy data. For participants enrolled in either the dose escalation or safety expansion phases, the maximum duration of treatment will be 12 months unless, in the opinion of the investigator and with the agreement of the sponsor, the participant would derive benefit from continued therapy beyond 12 months. Participants will make multiple visits to the clinic, and will have an end of treatment visit 30 days after the last dose of TAK-659 or NKTR-214 or before the start of subsequent alternative anticancer therapy, whichever occurs first. Participants will be followed for 90 days after the last dose or subsequent anti-cancer therapy, whichever occurs first, to permit the detection of any delayed treatment-related adverse events (AEs).
Sponsors
Nektar Therapeutics
Calithera Biosciences, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Histologically or cytologically confirmed diagnosis of advanced B-cell NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL) (Waldenstrom macroglobulinemia \[WM\] and chronic lymphocytic leukemia \[CLL\]/small lymphocytic leukemia \[SLL\] are excluded). 2. Radiographically or clinically measurable disease with at least 1 target lesion per (greater than \[\>\] 1.5 centimeter \[cm\] in the longest diameter for a lymph node or nodal mass, or \>1.0 cm in the longest diameter for extranodal disease) Lugano 2014 criteria for malignant lymphoma. 3. Participants who are refractory or relapsed after at least 2 prior lines of therapy due to progression, intolerance, or physician/participant decision, and for whom no effective standard therapy is available per the investigator's assessment. The sponsor may restrict prior lines of therapy in the expansion phase of the study based on emerging data. The decision may be documented and shared with investigators in a memo before the initiation of the dose expansion phase followed by updating the
Exclusion criteria
in a subsequent amendment, if deemed necessary. Requirements for prior therapy depending on disease type are outlined in the protocol, however all patients must be ineligible for or have already failed hematopoietic stem cell transplant. 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and life expectancy of \>3 months. 5. Must have adequate organ function. 6. Recovered (that is, less than or equal to \[\<=\] Grade 1 toxicity) from the clinically significant reversible effects of prior anticancer therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MTD of TAK-659 in Combination with NKTR-214 | 3 weeks after last dose of last participant in dose escalation or up to 6 months |
| RP2D of TAK-659 in Combination with NKTR-214 | 3 weeks after last dose of last participant in dose escalation or up to 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUCτ: Area Under the Plasma Concentration-time Curve From Time During the Dosing Interval for TAK-659 | Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days) | — |
| Cmax: Maximum Observed Plasma Concentration for NKTR-214 | Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days) | — |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for NKTR-214 | Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days) | — |
| Cmax: Maximum Observed Plasma Concentration for TAK-659 | Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days) | — |
| Overall Response Rate (ORR) | Through study completion, approximately 40 months | ORR is defined as the percentage of participants in the response-evaluable population who achieved either complete response (CR) or partial response (PR) as assessed by the investigator according to the Lugano 2014 criteria. |
| Duration of Response (DOR) | From first CR or PR to progressive disease (PD) or relapse (through study completion, approximately 40 months) | DOR is defined as the time from first CR or PR to PD or relapse in the response-evaluable population. |
| Progression-free Survival (PFS) | From first dose of study drug to PD or death (through study completion, approximately 40 months) | PFS is defined as the time from first dose to PD or death in the response-evaluable population. |
| AUC: Area Under the Plasma Concentration-time Curve for NKTR-214 | Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days) | — |
| Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 | Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days) | — |
Countries
Canada, United States
Outcome results
None listed