A Study of TAK-007 in Adults With Relapsed or Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL)

A Phase 2, Open-label, Multicenter Study of the Safety and Efficacy of TAK-007 in Adult Patients With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

This study has 2 parts.

The main aim of Part 1 is to check for side effects from TAK-007 in adults with relapsed or refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL),

The main aim of Part 2 is to learn whether lymphoma disease responds to treatment with TAK-007 in adults with r/r B-cell NHL or iNHL.

Participants will receive 3 days of chemotherapy to reduce a type of white blood cells called lymphocytes, in the blood. This is called lymphodepleting chemotherapy (LDC) or lymphodepletion. After LDC, patients will receive a single injection of TAK-007 or three weekly injections of TAK-007 (multi-dose injection). After this, participants will regularly visit the clinic for check-ups.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed or Refractory (r/r) B-cell Non-Hodgkin Lymphoma (NHL)
• Intervention / Treatment: Biological: TAK-007; Drug: Chemotherapy Agents

Detailed Description

The product being tested in this study is called TAK-007. TAK-007 is being tested to evaluate the safety and tolerability in adult participants with r/r B-cell NHL. The study will include 2 parts: Part 1 (Dose escalation and dose expansion) and Part 2.

In Part 1, dose escalation cohorts' participants will receive TAK-007 as follows:

Part 1 dose escalation:

• Part 1: Dose escalation: TAK-007 - 200×10^6 CD19-CAR+ Viable NK (Natural Killer) Cells (±30%)
• Part 1: Dose escalation: TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells (±25%)

In Part 1 dose expansion phase, separate expansion cohorts for LBCL and iNHL (Cohorts 1A [LBCL 3L+] and 2A [iNHL 3L+]) and two additional dose expansion cohorts with a multi-dose regimen will be added (i.e., Cohort 1B and 1C) to evaluate more than 1 doses of TAK-007 after a 3-day regimen of lymphodepleting chemotherapy.

Part 1 dose expansion cohorts' participants will receive TAK-007 as follows:

• Part 1: Dose expansion: Cohort 1 (LBCL 3L+): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells on Day 0 of the study.
• Part 1: Dose expansion: Cohort 2 (iNHL 3L+): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells on Day 0 of the study.

Based on the data in Part 1, a single TAK-007 dose level will be selected by the sponsor and investigators as the recommended phase 2 dose (RP2D).

Once RP2D is determined, participants will be enrolled in Part 2 of the study in the following cohorts:

• Cohort 1: TAK-007 (LBCL)
• Cohort 2: TAK-007 (iNHL)

This multi-center trial will be conducted worldwide. Part 1 of the study will be conducted in the US, and Part 2 will be conducted worldwide. The overall time to participate in this study is 5 years. Participants will make multiple visits to the clinic and will enroll in a separate, long-term, follow-up study for continued safety assessments for up to 15 years after TAK-007 administration.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • MedStar Georgetown University Medical Center
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center University of Miami Hospitals and Clinics
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern Memorial Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • The Bronx, New York, United States, 10467
      • Montefiore Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • DUHS Duke Blood Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Sidney Kimmer Cancer Center, Clinical Research Organization
  • Texas
    • Austin, Texas, United States, 78704
      • Saint Davids South Austin Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participants who have a life expectancy ≥12 weeks.
2. Participants who have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

3. Participants with a diagnosis of previously treated r/r histologically proven Cluster of Differentiation (CD)19 expressing disease of the following types:

   a. LBCL, including the following subtypes defined by the World Health Organization (WHO): i. Diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS). ii. High-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangement iii. HGBL NOS without translocations. iv. DLBCL arising from iNHL including follicular lymphoma (FL) or marginal zone lymphoma (MZL).

   v. T-cell/histiocyte-rich LBCL. vi. DLBCL associated with chronic inflammation. vii. Epstein-Barr virus-positive DLBCL-NOS. viii. Primary cutaneous DLBCL, leg type. ix. Primary mediastinal large B-cell lymphoma (PMBCL). x. FL Grade 3B. b. iNHL, including the following subtypes defined by the WHO: i. FL Grades 1, 2, 3A. ii. MZL (nodal, extranodal, and splenic).

4. Participants who have measurable disease, defined as at least 1 lesion per the Lugano classification. Lesions situated in a previously irradiated area are considered measurable if radiographic progression has been documented in such lesions following completion of radiation therapy. LBCL should have positron emission tomography (PET) -positive disease per the Lugano classification.

5. Participants who have r/r LBCL or r/r iNHL after ≥2 prior lines of systemic therapy: (Expansion Cohorts 1A and 1B [LBCL 3L+], and 2A [iNHL 3L +]) or r/r LBCL after 1 prior line of systemic therapy (Expansion Cohort 1C [LBCL 2L]):

   1. Participants with r/r LBCL must have received an anti-CD20 monoclonal antibody (mAb) and an anthracycline containing chemotherapy regimen and failed or be ineligible for high-dose chemotherapy and autologous stem cell transplantation (ASCT).
   2. Participants with iNHL must have received an anti-CD20 mAb and an alkylating agent (eg, bendamustine or cyclophosphamide).
   3. Preinduction salvage chemotherapy and ASCT should be considered 1 line of therapy.
   4. Any consolidation/maintenance therapy after a chemotherapy regimen (without intervening relapse) should be considered 1 line of therapy with the preceding combination therapy. Maintenance antibody therapy should not be considered a line of therapy.
   5. Single-agent anti-CD20 mAb therapy should not be considered a line of therapy.
   6. Bridging chemotherapy given just prior to CAR-T cell therapy treatment should be considered one line of therapy together with cell therapy.
   7. Participants who have received prior CD19-targeting CAR-T cell therapy must have achieved at least a partial response to the most recent CD19-targeting CAR-T cell therapy.

   8. Participants with 1 prior line of therapy in Part 1 Cohort 1C must have either:

      • refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy OR
      • relapsed or refractory disease and be ineligible for intensive chemoimmunotherapy and/or high-dose chemotherapy followed by ASCT due to comorbidities and/or age.

6. Participants who have adequate bone marrow function defined as follows:

   1. Absolute neutrophil count >500/μL.
   2. Platelet count of >50,000/μL at screening. Participants with transfusion-dependent thrombocytopenia are excluded.

7. Participants who have adequate renal, hepatic, cardiac, and pulmonary function as defined in the study protocol:

   1. Estimated glomerular filtration rate (GFR; Modification of Diet in Renal Disease equation [MDRD]) ≥30 mL/min.
   2. Serum alanine aminotransferase/aspartate aminotransferase ≤5 times the upper limit of normal range (ULN), as long as participant is asymptomatic.
   3. Total bilirubin ≤2 mg/dL. Participants with Gilbert's syndrome may have a bilirubin level >2 × ULN, per discussion between the investigator and the medical monitor.
   4. Left ventricular ejection fraction (LVEF) ≥40% as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed within 1 month of determination of eligibility.
   5. No evidence of clinically relevant pericardial effusion, and no acute clinically significant electrocardiogram (ECG) findings.
   6. Absence of Grade ≥2 pleural effusion. Grade 1 stable pleural effusions are allowed.
   7. Baseline oxygen saturation >92% on room air.
8. Participants are required to consent to provide either sufficient archived formalin-fixed paraffin embedded (at least 10 unstained slides, ideally 20 unstained slides) or fresh tumor tissue obtained after the last relapse (see laboratory manual for details). Exception may be granted by sponsor medical monitor per discussion with investigator.

Exclusion Criteria:

1. Participants with total body weight of <40 kg.
2. Participants with primary or secondary central nervous system (CNS) involvement by lymphoma. Participants with a history of secondary CNS involvement by lymphoma without evidence of CNS involvement at screening may be included.
3. Participants with Burkitt lymphoma, mantle cell lymphoma, lymphoplasmocytic lymphoma, or transformation from CLL/small lymphocytic lymphoma (Richter transformation).
4. Participants with a history of malignancy other than nonmelanoma skin cancer, carcinoma in situ (eg, cervix, bladder, breast), low-grade tumors deemed to be cured and not treated with systemic therapy (eg, by gastro-endoscopy curatively removed gastric cancer) or unless disease free for ≥3 years at screening.
5. Participants who have undergone autologous or allogeneic transplant or Chimeric antigen receptor T cells (CAR-T) or Chimeric antigen receptor Natural Killer cells (CAR-NK) therapy within 3 months of planned enrollment. Participants after allogeneic transplant have to be off systemic immunosuppressive therapy and without the evidence of clinically relevant acute or chronic graft-versus-host disease (GvHD) at the time of enrollment.
6. Treatment with any investigational products or any systemic anticancer treatment within 14 days or 2 half-lives of the treatment (whichever is longer) before conditioning therapy. For rituximab, a half-life of 22 days should be considered.
7. Participants with active infection, including fungal, bacterial, viral, or other infection that is uncontrolled or requires IV antimicrobials for management within 3 days before enrollment.
8. Participants with a history or presence of active or clinically relevant CNS disorder, such as seizure, encephalopathy, cerebrovascular ischemia/hemorrhage, severe dementia, cerebellar disease, or any autoimmune disease with CNS involvement. For CNS disorders that recover or are in remission, participants without recurrence within 2 years of planned study enrollment may be included.
9. Participants with any of the following within 6 months of enrollment: myocardial infarction, cardiac angioplasty or stenting, unstable angina, symptomatic congestive heart failure (ie, New York Heart Association Class II or greater), clinically significant arrythmia (including uncontrolled atrial fibrillation), or any other clinically significant cardiac disease.
10. Participants who have received a live vaccine ≤6 weeks before the start of the conditioning regime.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation: TAK-007 - 200×10^6 CD19-CAR+ Viable NK Cells; Participants received lymphodepleting chemotherapy per day intravenously (IV) for 3 days followed by TAK-007 200×10^6 anti-CD19 chimeric antigen receptor (CD19-CAR+) viable NK cells, single-dose, IV infusion, once on Day 0.	Biological: TAK-007; TAK-007 intravenous injection.; Drug: Chemotherapy Agents; Fludarabine and cyclophosphamide as per standard of care.
Experimental: Dose Escalation: TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells; Participants received lymphodepleting chemotherapy per day IV for 3 days followed by TAK-007 - 800×10^6 CD19-CAR+ viable NK cells, single-dose, IV infusion, once on Day 0.	Biological: TAK-007; TAK-007 intravenous injection.; Drug: Chemotherapy Agents; Fludarabine and cyclophosphamide as per standard of care.
Experimental: Dose Expansion: Cohort 1 (LBCL 3L+): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells; Participants with r/r LBCL received lymphodepleting chemotherapy per day IV for 3 days followed by TAK-007 at the dose level selected based on the dose escalation part (800×10^6 CD19-CAR+ viable NK cells), as a single-dose, IV infusion, once on Day 0 to determine recommended phase 2 dose (RP2D).	Biological: TAK-007; TAK-007 intravenous injection.; Drug: Chemotherapy Agents; Fludarabine and cyclophosphamide as per standard of care.
Experimental: Dose Expansion: Cohort 2 (iNHL 3L+): TAK-007 - 800×10^6 CD19-CAR+ Viable NK Cells; Participants with r/r iNHL received lymphodepleting chemotherapy per day IV for 3 days followed by TAK-007 at the dose level(s) selected based on the dose escalation part (800×10^6 CD19-CAR+ viable NK cells), as a single-dose, IV infusion, once on Day 0 to determine RP2D.	Biological: TAK-007; TAK-007 intravenous injection.; Drug: Chemotherapy Agents; Fludarabine and cyclophosphamide as per standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAE is defined as any event emerging or manifesting at or after the initiation of treatment with a study intervention or medicinal product or any existing event that worsens in either intensity or frequency following exposure to the study intervention or medicinal product.	Up to 24 months
Number of Participants With Clinically Significant Changes in Laboratory Parameters	Laboratory parameters included hematology, clinical chemistry, serum immunoglobulin and urinalysis tests.	Up to 24 months
Number of Participants With Notable Changes in Vital Signs	Vital signs included body temperature (oral or tympanic measurement), sitting blood pressure (after the participant had rested for at least 5 minutes), and pulse rate (beats per minute [bpm]).	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR Per Investigator	ORR is defined as the percentage of participants with CR or PR as best response to treatment, determined by the investigator per the Lugano 2014 criteria after TAK-007 administration. CR is defined as percentage of participants with target nodes/nodal masses must regress to ≤1.5 cm in the longest transverse diameter of all lesions and no extralymphatic sites of disease. PR is defined as ≥50% decrease in sum of the product of the perpendicular diameters of up to 6 target measurable nodes and extranodal sites; absent/normal, regressed, but no increase in nonmeasured lesion; Spleen must have regressed by >50% in length beyond normal.	Up to 24 months
Complete Response (CR) Per Investigator	CR is defined per Lugano 2014 criteria as percentage of participants with target nodes/nodal masses must regress to ≤1.5 cm in the longest transverse diameter of all lesions and no extralymphatic sites of disease.	Up to 24 months
Duration of Response (DOR) Per Investigator	DOR is defined only for participants who experienced objective response (complete response or partial response) and is the time from the date of first documented objective response to the date of first documented disease progression or death, whichever comes first. Participants not meeting the criteria for progression or death will be censored at the last disease assessment.	Up to 24 months
Progression-free Survival (PFS) Per Investigator	Progression-free survival is defined as the time from TAK-007 administration to the date of disease progression or death from any cause, whichever comes first. Participants who do not have disease progression or die were censored at the last disease assessment. Participants who do not have postbaseline disease assessment prior to new anticancer therapy (excluding SCT) in the absence of death were censored at the dosing date of TAK-007.	Up to 24 months
Overall Survival (OS)	OS is defined as the time from TAK-007 administration to the date of death. Participants who did not die were censored at the last contact date.	Up to 24 months
Cmax - Maximum Observed Blood Concentration of TAK-007	The unit of measure 'copies per microgram' indicates copies of TAK-007 transgene per micrograms of genomic deoxyribonucleic acid (DNA).	At 1 hour (±15 minutes) predose and postdose (Day 0) and once on Days 1, 3, 7, 10, 14, 21, 28/Month 1, Months 2, 3, 4, 6, 9, 12, 18, 24
Tmax - Time of First Occurrence of Cmax of TAK-007		At 1 hour (±15 minutes) predose and postdose (Day 0) and once on Days 1, 3, 7, 10, 14, 21, 28/Month 1, Months 2, 3, 4, 6, 9, 12, 18, 24
Tlast - Time of Last Measurable Concentration Above the Lower Limit of Quantitation of TAK-007		At 1 hour (±15 minutes) predose and postdose (Day 0) and once on Days 1, 3, 7, 10, 14, 21, 28/Month 1, Months 2, 3, 4, 6, 9, 12, 18, 24
AUClast - Area Under the Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration of TAK-007	The unit of measure 'day*copies/µg' indicates day*copies of TAK-007 transgene per µg of genomic DNA.	At 1 hour (±15 minutes) predose and postdose (Day 0) and once on Days 1, 3, 7, 10, 14, 21, 28/Month 1, Months 2, 3, 4, 6, 9, 12, 18, 24
Concentration of Interleukin (IL)-15 and Other Soluble Immune Factors in Plasma Over Time	Concentration of IL-15 and soluble immune factors (eg, Interferon (IFN)-gamma (γ) and IL-6) in plasma over time were reported.	Baseline, pre-dose (Day 0) and post-dose at Days 1, 7, 14, 21, 28 and Months 2,3,4,6,9,12
Percentage of Participants With B-cell Aplasia Before and After TAK-007 Administration	B-cell aplasia is defined as <50 B-cells per microliters (µl) of blood.	Pre-dose at Days -5, -4, 0 and post-dose at Days 0, 7, 28 and Months 2, 3, 4, 6, 9, 12
Percentage of Participants With Detectable Anti-human Leukocyte Antigen (HLA) and Anti-chimeric Antigen Receptor (CAR) Antibodies Before (Prevalence) and After (Incidence) TAK-007 Administration Over Time		Up to 12 months
Percentage of Participants With Positive Replication Competent Retrovirus (RCR) Test Results Before (Prevalence) and After (Incidence) TAK-007 Administration Over Time		Up to 60 months

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Medical Director, Takeda

Publications and helpful links

Helpful Links

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• Click here for more information about this trial in easy-to-understand language, including a Plain Language Summary of the results if the trial has been completed.

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2021
• Primary Completion (Actual): June 16, 2024
• Study Completion (Estimated): December 20, 2038

Study Registration Dates

• First Submitted: August 20, 2021
• First Submitted That Met QC Criteria: August 20, 2021
• First Posted (Actual): August 25, 2021

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Drug Therapy; Allogeneic; Cell therapy; Chimeric antigen receptor; Natural killer cells
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, B-Cell
• Other Study ID Numbers: TAK-007-2001; 2021-002086-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No