Overview

A Study of TAK-659 in Adult Participants With Advanced Solid Tumor and Lymphoma Malignancies

Status:
Completed
Trial end date:
2021-06-29
Target enrollment:
0
Participant gender:
All
Summary
This study is an open-label, multicenter, phase 1, dose escalation study of TAK-659 in adult participants with advanced solid tumor and lymphoma malignancies. This study will be the first to administer TAK-659 to humans. The participants population during dose escalation (Part A) will consist of adults previously diagnosed with any form of a solid tumor or lymphoma for which standard, curative, or life-prolonging treatment does not exist or is no longer effective. This first-in-human (FIH) study will include 5 dose expansion cohorts in refractory and/or relapsed Chronic Lymphocytic Leukemia (CLL), Diffuse Large B Cell Lymphoma (DLBCL), indolent Non Hodgkin Lymphoma (iNHL), Mantle Cell Lymphoma (MCL), Post Transplant Lymphoproliferative Disorder (PTLD) (Part B) following completion of dose escalation (Part A).
Phase:
Phase 1
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Millennium Pharmaceuticals, Inc.
Criteria
Inclusion Criteria:

Each participant must meet all of the following inclusion criteria to be enrolled in the
study:

1. Male or female participants 18 years or older.

2. To be enrolled to the dose escalation (Part A), participants must have

1. histologically or cytologically confirmed diagnosis of metastatic and/or advanced
solid tumor malignancy or lymphoma, for which no effective standard treatment is
available. However, participants with primary brain tumors or WM will be
excluded.

2. Radiographically or clinically measurable or nonmeasurable (but evaluable)
disease. Radiographically measurable disease is determined by RECIST (version
1.1) for solid tumors or by International Working Group (IWG) criteria for
malignant lymphoma (2007 IWG).

3. To be enrolled to the dose expansion cohorts (Part B), participants must meet the
following criteria:

1. Diagnosis of CLL that meets International Workshop on Chronic Lymphocytic
Leukemia (IWCLL) 2008 criteria for Cohort 1; pathologically confirmed diagnosis
of DLBCL for Cohort 2; histologically confirmed diagnosis of B-cell NHL
(follicular lymphoma [FL] [Grade 1, 2, or 3a], small lymphocytic lymphoma (SLL),
lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM), marginal zone
lymphoma (MZL) [splenic, nodal, or extra-nodal]) for Cohort 3; histologically
confirmed diagnosis of MCL for Cohort 4; and histologically confirmed diagnosis
of PTLD (early lesion, polymorphic, monomorphic, classical Hodgkin lymphoma-type,
Epstein-Barr virus (EBV) -positive DLBCL of the elderly, DLBCL associated with
chronic inflammation; along with documented or documentable Epstein-Barr
virus-encoded small RNA (EBER) status by tissue in situ hybridization [ISH]) for
Cohort 5; histologically confirmed DLBCL (de novo or transformed disease from
iNHL) for Cohort 6.

2. Must have received greater than or equal to (>=) 1 prior therapy (excluding
radiation); documented PD (MCL); either treatment naïve to, relapsed/refractory
to, or treatment failure due to other reasons with ibrutinib, idelalisib, or any
other investigational B-cell receptor (BCR) in pathway inhibitors not directly
targeting Spleen tyrosine kinase (SYK); considered not appropriate for treatment
or retreatment with purine analog-based therapy (CLL); or considered ineligible
for at least 1 prior therapy (PTLD); or relapsed or refractory to >= 2 prior
lines of chemotherapy (including standard first line therapy including Rituximab
and an anthracycline [or equivalent if contraindicated] and one additional
systemic multiagent chemotherapy as second-line salvage therapy that may have
included autologous stem cell transplant (ASCT) [unless ineligible for salvage
therapy and ASCT]) and should not have failed more than 4 prior lines of therapy
(DLBCL Cohort 6).

3. Radiographically or clinically measurable and/or evaluable disease as specified
in the protocol.

4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

5. Participants must have adequate organ function, including bone marrow reserve,
hepatic, renal, pancreatic function and controlled blood pressure as described in the
protocol.

6. Female participants who are postmenopausal for at least 1 year, are surgically
sterile, or if of childbearing potential who agree to use 2 effective method(s) of
contraception during the study treatment period through 6 months after the last dose
of study drug or practice true abstinence.

Male participants, even if surgically sterilized, who agree to practice effective
barrier contraception during the study treatment period through 6 months after the
last dose of study drug or practice true abstinence.

7. Voluntary written consent must be given before performance of any study related
procedure not part of standard medical care, with the understanding that consent may
be withdrawn by the participant at any time without prejudice to future medical care.

8. Participants must have recovered from the reversible effects of prior anticancer
therapy (to Grade less than or equal to (<=) 1).

Exclusion Criteria:

Participants meeting any of the following exclusion criteria are not to be enrolled in the
study.

1. Participants with brain metastasis, or participants with central nervous system (CNS)
lymphoma or participants with another malignancy within two years of study start, with
exceptions as described in the protocol.

2. Any serious medical or psychiatric illness, including drug or alcohol abuse, that
could, in the investigator's opinion, potentially interfere with the completion of
treatment according to this protocol.

3. Life-threatening illness unrelated to cancer; major surgery within 14 days before the
first dose of study drug; systemic infection requiring intravenous (IV) antibiotic
therapy or other serious infection (bacterial, fungal, or viral) within 21 days before
the first dose of study drug.

4. Female participants who are pregnant or lactating.

5. Any immunotherapy, chemotherapy, radiotherapy, or investigational therapy within 3-4
weeks before the first dose of study treatment, as detailed in the protocol.

6. For escalation cohort or expansion cohorts excluding PTLD, ASCT within 6 months before
Day 1 of Cycle 1, or prior ASCT at any time without full hematopoietic recovery before
Day 1 of Cycle 1, or prior allogeneic stem cell transplant at any time.

7. Treatment with high dose corticosteroids (> daily dose equivalent to 10 milligram (mg)
oral prednisone) for anticancer purposes within 7 days before the first dose of
TAK-659.

8. Known human immunodeficiency virus (HIV) positive; known hepatitis B surface
antigen-positive; or known or suspected active hepatitis C infection (testing not
required).

9. Evidence of currently uncontrolled cardiovascular conditions as listed in the
protocol.

10. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral
absorption or tolerance of TAK-659 including difficulty swallowing tablets; diarrhea >
Grade 1 despite supportive therapy.

11. Lack of suitable venous access for required blood sampling.

12. Use or consumption of P-glycoprotein (P-gp) inducers/inhibitors and/or strong CYP3A
inducers/inhibitors as described in the protocol, and grapefruit-containing food or
beverages as described in the protocol.