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

• Sponsor: Janssen Research & Development, LLC (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04540796
• Collaborator: (none)
• Enrollment: 120
• Locations: 39
• Arms: 2
• Anticipated Duration (Months): 39.5
• Patients Per Site: 3.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell	Drug: JNJ-75348780	Phase 1

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 120 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Nov 20, 2020
• Anticipated Primary Completion Date: May 11, 2023
• Anticipated Study Completion Date: Mar 5, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A: Dose Escalation 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.	Drug: JNJ-75348780; Participants will receive JNJ-75348780 by subcutaneous (SC) administration.
Experimental: Part B: Cohort Expansion Participants will receive JNJ-75348780 at one of the putative RP2Ds determined in Part A.	Drug: JNJ-75348780; Participants will receive JNJ-75348780 by subcutaneous (SC) administration.

Outcome Measures

Primary Outcome Measures

1. 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]

   An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

2. Part A and Part B: Number of Participants with AEs by Severity [Up to 2 years 10 months]

   Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.

3. Part A and Part B: Number of Participants with Dose-Limiting Toxicity (DLT) [Up to 28 days]

   Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.

Secondary Outcome Measures

1. Area Under the Concentration-time Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-75348780 [Up to 2 years 10 months]

   AUCtau is the measure of the serum drug concentration from time zero to end of dosing interval.

2. Maximum Observed Serum Concentration (Cmax) of JNJ-75348780 [Predose, 48 hours postdose (up to 2 years 10 months)]

   Cmax is the maximum observed serum concentration of JNJ-75348780.

3. Minimum Observed Serum Concentration (Cmin) of JNJ-75348780 [Predose, 48 hours postdose (up to 2 years 10 months)]

   Cmin is the minimum observed serum concentration of JNJ-75348780.

4. Objective Response Rate (ORR) [Up to 2 years 10 months]

   ORR is defined as the percentage of participants who achieve a partial response (PR) or better according to the revised response criteria for malignant lymphoma, the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) response criteria and International Workshop for Waldenstrom Macroglobulinemia (IWWM) response criteria.

5. Complete Response (CR) Rate [Up to 2 years 10 months]

   CR rate is defined as the percentage of participants who achieve a best response of CR according to the revised response criteria for malignant lymphoma, iwCLL response criteria and IWWM response criteria.

6. Time to Response (TTR) [Up to 2 years 10 months]

   TTR is defined for participants who achieved PR or CR as the time from the first dose of study drug to first response of PR or CR according to the revised response criteria for malignant lymphoma, iwCLL response criteria and IWWM response criteria.

7. Duration of Response (DOR) [Up to 2 years 10 months]

   DOR is defined for participants who achieved PR or CR as the time between the date of initial documentation of PR or CR to the date of either the first documented evidence of disease progression or death according to the revised response criteria for malignant lymphoma, iwCLL response criteria and IWWM response criteria.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
3	University of Oklahoma Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104
4	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
5	St. Vincent's Hospital Sydney	Darlinghurst		Australia	2010
6	Austin Hospital	Heidelberg		Australia	3084
7	Linear Clinical Research Ltd	Nedlands		Australia	6009
8	Beijing Cancer Hospital	Beijing		China	100142
9	Beijing Tongren Hospital, CMU	Beijing		China	102600
10	Sun Yat-Sen University Cancer Center	Guangzhou		China	510060
11	Zhejiang Cancer Hospital	Hang Zhou		China	310022
12	CHRU de Lille - Hôpital Claude Huriez	Lille		France	59037
13	CHU Nantes	NANTES Cedex 1		France	44093
14	Centre hospitalier Lyon-Sud	Pierre Benite		France	69495
15	Rambam Medical Center	Haifa		Israel	31096
16	Carmel Medical Center	Haifa		Israel	34362
17	Hadassah Medical Center	Jerusalem		Israel	9112001
18	Sheba Medical Center	Ramat Gan		Israel	74047
19	Tel Aviv Sourasky MC	Tel Aviv		Israel	6423906
20	Seoul National University Hospital	Seoul		Korea, Republic of	03080
21	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
22	Asan Medical Center	Seoul		Korea, Republic of	05505
23	Samsung Medical Center	Seoul		Korea, Republic of	06351
24	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
25	Hospital de Vall D'Hebron	Barcelona		Spain	08035
26	Hosp. Univ. Germans Trias I Pujol	Barcelona		Spain	8916
27	Hosp. Univ. Fund. Jimenez Diaz	Madrid		Spain	28040
28	Clinica Univ. de Navarra	Pamplona		Spain	31008
29	Hosp. Clinico Univ. de Salamanca	Salamanca		Spain	37007
30	Chang-Gung Memorial Hospital, Kaohsiung	Kaohsiung		Taiwan	83301
31	China Medical University Hospital	Taichung		Taiwan	40402
32	Taichung Veterans General Hospital	Taichung		Taiwan	40705
33	National Cheng Kung University Hospital	Tainan		Taiwan	70403
34	National Taiwan University Hospital	Taipei		Taiwan	10048
35	Birmingham Heartlands Hospital	Birmingham		United Kingdom	B9 5ST
36	Leicester Royal Infirmary	Leicester		United Kingdom	LE1 5WW
37	King's College Hospital	London		United Kingdom	SE5 9RS
38	The Christie Nhs Foundation Trust	Manchester		United Kingdom	M20 4BX
39	Plymouth Hospital NHS Trust	Plymouth		United Kingdom	PL6 8DH

Sponsors and Collaborators

• Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT04540796
• Other Study ID Numbers: CR108882; 2020-001183-29; 75348780LYM1001
• First Posted: Sep 7, 2020
• Last Update Posted: Aug 12, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell

Study Results

No Results Posted as of Aug 12, 2022