A Study of JNJ-75348780 in Participants With Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

A Phase 1, First-in-Human, Dose Escalation Study of the JNJ-75348780 Bispecific Antibody Targeting CD3 and CD22 in Participants With NHL and CLL

Sponsors

Lead Sponsor: Janssen Research & Development, LLC

Source Janssen Research & Development, LLC
Brief Summary

The purpose of this study is to characterize safety and to determine the putative recommended Phase 2 dose(s) (RP2D[s]) and optimal dosing schedule(s) of JNJ-75348780 in participants with relapsed/ refractory B-cell Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL) in Part A and to further characterize the safety at the RP2D(s) in Part B.

Detailed Description

B-cell lymphoid malignancies include CLL and NHL and are defined by clonal populations of B-lymphocytes expressing identical surface antigens. CD22 is a surface protein specifically expressed on B-lymphocytes and is expressed in B-lymphocytic malignancies. It is known to negatively regulate the B-cell receptor via its cytosolic immunoreceptor tyrosine-based inhibitory motifs. JNJ-75348780 is a novel human bispecific antibody that recognizes the CD3 antigen on T-lymphocytes and the CD22 antigen on mature and malignant B-lymphocytes. JNJ-75348780 is hypothesized to lead to cytotoxicity, T-cell activation, and induction of cytokines upon engagement of CD3 on T-cells and CD22 on malignant B-lymphocytes. The study consists of screening phase, treatment phase and post-treatment phase. The total study duration will be up to 2 years 10 months. Efficacy assessments will include radiographic image assessments, positron emission tomography scan, bone marrow assessment, endoscopy or colonoscopy, physical examinations. Safety will be monitored throughout the study.

Overall Status Recruiting
Start Date 2020-11-20
Completion Date 2024-03-05
Primary Completion Date 2023-05-11
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Part A and Part B: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability Up to 2 years 10 months
Part A and Part B: Number of Participants with AEs by Severity Up to 2 years 10 months
Part A and Part B: Number of Participants with Dose-Limiting Toxicity (DLT) Up to 28 days
Secondary Outcome
Measure Time Frame
Area Under the Concentration-time Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-75348780 Up to 2 years 10 months
Maximum Observed Serum Concentration (Cmax) of JNJ-75348780 Predose, 48 hours postdose (up to 2 years 10 months)
Minimum Observed Serum Concentration (Cmin) of JNJ-75348780 Predose, 48 hours postdose (up to 2 years 10 months)
Objective Response Rate (ORR) Up to 2 years 10 months
Complete Response (CR) Rate Up to 2 years 10 months
Time to Response (TTR) Up to 2 years 10 months
Duration of Response (DOR) Up to 2 years 10 months
Enrollment 120
Condition
Intervention

Intervention Type: Drug

Intervention Name: JNJ-75348780

Description: Participants will receive JNJ-75348780 by subcutaneous (SC) administration.

Eligibility

Criteria:

Inclusion Criteria: - Histologic documentation of disease: B-cell NHL or CLL requiring therapy; All participants must have relapsed or refractory disease with no other approved therapies available that would be more appropriate in the investigator's judgment. B cell NHL as defined per the 2016 World Health Organization (WHO) classification: In addition, the following disease-specific criteria outlined below must be met a) If diffuse large B-cell lymphoma (DLBCL): received, or not eligible for high-dose chemotherapy and autologous stem cell transplantation with curative intent, b) If follicular lymphoma (FL)/ marginal zone lymphoma (MZL) (except mucosa-associated lymphoid tissue [MALT]), or Waldenstrom macroglobulinemia (WM): previously treated with a minimum of 2 prior lines of systemic therapy, with at least 1 prior line containing an anti-CD20 antibody, c) If mantle cell lymphoma (MCL): previously treated with at least 1 prior line of systemic therapy containing an anti-CD20 antibody. CLL or small lymphocytic lymphoma (SLL): relapsed or refractory with at least 2 prior lines of therapy to include a bruton tyrosine kinase inhibitor (BTKi) and/or a B-cell lymphoma (BCL)2 inhibitor, if eligible. For Part B: participants must have measurable disease as defined by the appropriate disease response criteria - Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0 or 1 - Cardiac parameters within the following range: corrected QT interval (QTc intervals corrected using Fridericia's formula [QTcF]) less than or equal to (<=) 480 milliseconds (ms) based on the average of triplicate assessments performed no more than 5 (plus minus [+ -] 3) minutes apart - Women of childbearing potential must have a negative highly sensitive serum pregnancy test (Beta human chorionic gonadotropin) at screening and prior to the first dose of study drug - Women must be: a) not of childbearing potential, b) of childbearing potential and practicing a highly effective, preferably user independent method of contraception (failure rate of less than (<) 1 percent (%) per year when used consistently and correctly) and agrees to remain on a highly effective method while receiving study drug and until 90 days after last dose Exclusion Criteria: - Known active central nervous system (CNS) involvement with lymphoma - Prior solid-organ transplantation - Either of the following: a) received an autologous stem cell transplant <=3 months before the first dose of JNJ 75348780, b) prior treatment with allogenic stem cell transplant <= 6 months before the first dose of JNJ-75348780, or has evidence of graft versus host disease that requires immunosuppressant therapy - Prior chemotherapy, targeted therapy, immunotherapy or radiotherapy (with the exclusion of palliative radiation to limited sites that do not interfere with response assessment based on a sufficient number of other sites), within 2 weeks before the first administration of study drug. For investigational agents where the half-life is known, there should be a treatment-free window of at least 2 weeks or 5 half-lives, whichever is longer. For investigational agents with long half-lives a wash-out of 4 weeks is acceptable. Participants who received prior treatment with anti-CD20 * anti-CD3 bispecific therapy will be excluded until a dedicated cohort(s) is opened as determined by the SET - Active autoimmune disease that requires systemic immunosuppressive medications (example, chronic corticosteroid, methotrexate, or tacrolimus) - History of malignancy (other than the disease under study in the cohort to which the participant is assigned) within 1 year prior to the first administration of study drug. Exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy which in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 1 year before the first dose of study drug. Concomitant malignancies that are unlikely to progress and/or preclude evaluation of study endpoints may be allowed after discussion with the Study Responsible Physician

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Janssen Research & Development, LLC Clinical Trial Study Director Janssen Research & Development, LLC
Overall Contact

Last Name: Study Contact

Phone: 844-434-4210

Email: [email protected]

Location
Facility: Status:
University of Alabama at Birmingham | Birmingham, Alabama, 35233, United States Recruiting
Icahn School of Medicine at Mount Sinai | New York, New York, 10029, United States Not yet recruiting
University of Oklahoma Stephenson Cancer Center | Oklahoma City, Oklahoma, 73104, United States Not yet recruiting
The University of Texas MD Anderson Cancer Center | Houston, Texas, 77030, United States Recruiting
St. Vincent's Hospital Sydney | Darlinghurst, 2010, Australia Withdrawn
Austin Hospital | Heidelberg, 3084, Australia Recruiting
Linear Clinical Research Ltd | Nedlands, 6009, Australia Recruiting
Beijing Cancer Hospital | Beijing, 100142, China Not yet recruiting
Beijing Tongren Hospital, CMU | Beijing, 102600, China Not yet recruiting
Sun Yat-Sen University Cancer Center | Guangzhou, 510060, China Not yet recruiting
Zhejiang Cancer Hospital | Hang Zhou, 310022, China Not yet recruiting
CHRU de Lille - Hôpital Claude Huriez | Lille, 59037, France Recruiting
CHU Nantes | NANTES Cedex 1, 44093, France Recruiting
Centre hospitalier Lyon-Sud | Pierre Benite, 69495, France Recruiting
Rambam Medical Center | Haifa, 31096, Israel Recruiting
Carmel Medical Center | Haifa, 34362, Israel Recruiting
Hadassah Medical Center | Jerusalem, 9112001, Israel Recruiting
Sheba Medical Center | Ramat Gan, 74047, Israel Recruiting
Tel Aviv Sourasky MC | Tel Aviv, 6423906, Israel Recruiting
Seoul National University Hospital | Seoul, 03080, Korea, Republic of Recruiting
Severance Hospital, Yonsei University Health System | Seoul, 03722, Korea, Republic of Recruiting
Asan Medical Center | Seoul, 05505, Korea, Republic of Recruiting
Samsung Medical Center | Seoul, 06351, Korea, Republic of Recruiting
The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul, 06591, Korea, Republic of Recruiting
Hospital de Vall D'Hebron | Barcelona, 08035, Spain Recruiting
Hosp. Univ. Germans Trias I Pujol | Barcelona, 8916, Spain Recruiting
Hosp. Univ. Fund. Jimenez Diaz | Madrid, 28040, Spain Recruiting
Clinica Univ. de Navarra | Pamplona, 31008, Spain Recruiting
Hosp. Clinico Univ. de Salamanca | Salamanca, 37007, Spain Recruiting
Chang-Gung Memorial Hospital, Kaohsiung | Kaohsiung, 83301, Taiwan Recruiting
China Medical University Hospital | Taichung, 40402, Taiwan Recruiting
Taichung Veterans General Hospital | Taichung, 40705, Taiwan Recruiting
National Cheng Kung University Hospital | Tainan, 70403, Taiwan Recruiting
National Taiwan University Hospital | Taipei, 10048, Taiwan Recruiting
Birmingham Heartlands Hospital | Birmingham, B9 5ST, United Kingdom Withdrawn
Leicester Royal Infirmary | Leicester, LE1 5WW, United Kingdom Recruiting
King's College Hospital | London, SE5 9RS, United Kingdom Recruiting
The Christie Nhs Foundation Trust | Manchester, M20 4BX, United Kingdom Recruiting
Plymouth Hospital NHS Trust | Plymouth, PL6 8DH, United Kingdom Recruiting
Location Countries

Australia

China

France

Israel

Korea, Republic of

Spain

Taiwan

United Kingdom

United States

Verification Date

2022-08-01

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Part A: Dose Escalation

Type: Experimental

Description: Participants will receive once weekly dose or may receive every 2 weeks (Q2W) administration of JNJ-75348780. The dose levels will be escalated sequentially based on the decisions of the Study Evaluation Team (SET), along with the potential exploration of other routes of administration and schedules, until one or more recommended Phase 2 Doses (RP2D) have been identified.

Label: Part B: Cohort Expansion

Type: Experimental

Description: Participants will receive JNJ-75348780 at one of the putative RP2Ds determined in Part A.

Patient Data Yes
Study Design Info

Allocation: Non-Randomized

Intervention Model: Sequential Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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