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A Study of TAK-659 in Combination With NKTR-214 in Participants With Advanced Non-Hodgkin Lymphoma (NHL)

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ClinicalTrials.gov Identifier: NCT03772288
Recruitment Status : Not yet recruiting
First Posted : December 11, 2018
Last Update Posted : December 11, 2018
Sponsor:
Collaborator:
Nektar Therapeutics
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

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.

Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin Drug: TAK-659 Drug: NKTR-214 Phase 1

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 NHL after 2 but no more than 3 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/MAD 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 standard 3+3 dose escalation schema. TAK-659 60 mg + NKTR-214 0.003 mg/kg is the starting dose. Participants could also receive 40 mg, 80 mg or 100 mg QD TAK-659 during dose escalation and .003mg/kg or .006mg/kg of NKTR-214. Alternative regimens 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 MAD 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 the start of subsequent alternative anticancer therapy, whichever occurs first. Participants will be followed for 90 days after the last dose to permit the detection of any delayed treatment-related adverse events (AEs).


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Study of TAK-659 in Combination With NKTR-214 in Patients With Advanced Non-Hodgkin Lymphoma
Estimated Study Start Date : January 23, 2019
Estimated Primary Completion Date : November 10, 2021
Estimated Study Completion Date : November 17, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: Dose Escalation: TAK-659 + NKTR-214
TAK-659 tablet, orally, once daily along with NKTR-214, infusion, intravenously, once on Day 1 in a 21-day treatment cycle, until disease progression, unacceptable toxicities, or discontinuation by participant. The dose escalation phase will determine the MTD or maximally administered dose (MAD) or RP2D of TAK-659. Dose escalation of TAK-659 will be based on available safety and tolerability data.
Drug: TAK-659
Tablets.

Drug: NKTR-214
Intravenous infusion.

Experimental: Safety Expansion: TAK-659 + NKTR-214
TAK-659, tablet, orally, once daily along with NKTR-214, infusion, intravenously, once on Day 1 of 21-day treatment cycle, until disease progression, unacceptable toxicities, or discontinuation by participants. TAK-659 and NKTR-214 MTD/RP2D will be determined from the dose escalation phase.
Drug: TAK-659
Tablets.

Drug: NKTR-214
Intravenous infusion.




Primary Outcome Measures :
  1. MTD of TAK-659 in Combination with NKTR-214 [ Time Frame: Up to 6 months ]
  2. RP2D of TAK-659 in Combination with NKTR-214 [ Time Frame: Up to 6 months ]

Secondary Outcome Measures :
  1. Cmax: Maximum Observed Plasma Concentration for TAK-659 [ Time Frame: Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days) ]
  2. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 [ Time Frame: Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days) ]
  3. AUCτ: Area Under the Plasma Concentration-time Curve From Time During the Dosing Interval for TAK-659 [ Time Frame: Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days) ]
  4. Cmax: Maximum Observed Plasma Concentration for NKTR-214 [ Time Frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days) ]
  5. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for NKTR-214 [ Time Frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days) ]
  6. AUC: Area Under the Plasma Concentration-time Curve for NKTR-214 [ Time Frame: Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days) ]
  7. Overall Response Rate (ORR) [ Time Frame: Up to 6 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.

  8. Duration of Response (DOR) [ Time Frame: From first CR or PR to progressive disease or relapse (up to 6 months) ]
    DOR is defined as the time from first CR or PR to progressive disease or relapse in the response-evaluable population.

  9. Time to Progression (TTP) [ Time Frame: From first dose to progressive disease or relapse (up to 6 months) ]
    TTP is defined as the time from first dose to PD or relapse in the response-evaluable population. Progressive disease is defined as any new lesion or increase by greater than (>) 50 percent (%) of previously involved sites.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically confirmed diagnosis of advanced NHL of any histology (with the exception of participants with Waldenstrom macroglobulinemia [WM] and chronic lymphocytic leukemia [CLL]).
  2. Radiographically or clinically measurable disease with at least 1 target lesion per Lugano 2014 criteria for malignant lymphoma.
  3. Participants who are refractory or relapsed after at least 2 prior lines of therapy but no more than 3 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. Requirements for prior therapy depending on disease type are outlined in the protocol, however all patients must be ineligible for 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.

Exclusion Criteria:

  1. Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or computed tomography (CT) scan/magnetic resonance imaging. Exceptions include those participants who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids, and do not have neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
  2. Known HIV infection or HIV-related malignancy, hepatitis B surface antigen positive, or known or suspected active hepatitis C infection.
  3. History of drug-induced pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  4. Systemic anticancer treatment (including investigational agents) or radiotherapy less than 2 weeks before the first dose of study treatment (<=4 weeks for antibody-based therapy including unconjugated antibody, antibody-drug conjugate, and bi-specific T-cell engager agents; <=8 weeks for cell-based therapy or antitumor vaccine).
  5. Prior chimeric antigen receptor T-cell (CAR-T) therapy.
  6. Participants in need of immediate cytoreductive therapy.
  7. Prior autologous stem cell transplant (ASCT) within 12 months or prior ASCT at any time without full hematopoietic recovery before Cycle 1 Day 1 or allogeneic stem cell transplant any time.
  8. Prior treatment with a SYK inhibitor or interleukin-2 (IL-2) therapy.
  9. Active, known, or suspected autoimmune disease. Participants requiring systemic treatment within the past 3 months or with a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents. (Exceptions include any patient taking 10 mg or less of prednisone or equivalent, participants with vitiligo, hypothyroidism stable on hormone replacement, type 1 diabetes, Graves disease, Hashimoto disease, alopecia areata, eczema, or with medical monitor approval.)
  10. History of organ or tissue transplant that requires systemic use of immunosuppressive agents.
  11. Major surgery within 14 days before the first dose of study drug and not recovered fully from any complications from surgery or systemic infection requiring intravenous antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
  12. Use of >2 antihypertensive medications for management of hypertension (including diuretics).
  13. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of TAK-659, including difficulty swallowing tablets or diarrhea Grade >1 despite supportive therapy.
  14. Treatment with high-dose corticosteroids for anticancer purposes within 14 days before the first dose of TAK-659; daily dose equivalent to 10 mg oral prednisone or less is permitted.
  15. Use or consumption of:

    • Medications or supplements that are known to be inhibitors of P-gp and/or strong reversible inhibitors of cytochrome (CYP3A), strong CYP3A mechanism-based inhibitors, strong CYP3A inducers or P-gp inducers within 5 times the inhibitor half-life or within 7 days before the first dose of study drug. In general, the use of these agents is not permitted during the study except in cases in which an AE must be managed.
    • Grapefruit-containing food or beverages within 5 days before the first dose of study drug. Note that grapefruit-containing food and beverages are not permitted during the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03772288


Contacts
Contact: Takeda Study Registration Call Center +1-866-835-2233 globaloncologymedinfo@takeda.com

Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Nektar Therapeutics
Investigators
Study Director: Medical Director Millennium Pharmaceuticals, Inc.

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03772288     History of Changes
Other Study ID Numbers: C34015
U1111-1218-4372 ( Registry Identifier: WHO )
First Posted: December 11, 2018    Key Record Dates
Last Update Posted: December 11, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: "Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment."

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases