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

• ClinicalTrials.gov Identifier: NCT04540796
• Recruitment Status: Recruiting
• First Posted: September 7, 2020
• Last Update Posted: May 20, 2022
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: September 2, 2020
• First Posted Date: September 7, 2020
• Last Update Posted Date: May 20, 2022
• Actual Study Start Date: November 20, 2020
• Estimated Primary Completion Date: May 11, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 21, 2022)

• Part A and Part B: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: 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.
• Part A and Part B: Number of Participants with AEs by Severity [ Time Frame: 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.
• Part A and Part B: Number of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: September 2, 2020)

• Part A and Part B: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Up to 2.7 years ]
  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.
• Part A and Part B: Number of Participants with AEs by Severity [ Time Frame: Up to 2.7 years ]
  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.
• Part A and Part B: Number of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: Up to 14 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.

Current Secondary Outcome Measures (submitted: January 21, 2022)

• Area Under the Concentration-time Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-75348780 [ Time Frame: Up to 2 years 10 months ]
  AUCtau is the measure of the serum drug concentration from time zero to end of dosing interval.
• Maximum Observed Serum Concentration (Cmax) of JNJ-75348780 [ Time Frame: Predose, 48 hours postdose (up to 2 years 10 months) ]
  Cmax is the maximum observed serum concentration of JNJ-75348780.
• Minimum Observed Serum Concentration (Cmin) of JNJ-75348780 [ Time Frame: Predose, 48 hours postdose (up to 2 years 10 months) ]
  Cmin is the minimum observed serum concentration of JNJ-75348780.
• Objective Response Rate (ORR) [ Time Frame: 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.
• Complete Response (CR) Rate [ Time Frame: 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.
• Time to Response (TTR) [ Time Frame: 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.
• Duration of Response (DOR) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: September 2, 2020)

• Area Under the Concentration-time Curve From Time Zero to End of Dosing Interval (AUCtau) of JNJ-75348780 [ Time Frame: Up to 2.7 years ]
  AUCtau is the measure of the serum drug concentration from time zero to end of dosing interval.
• Maximum Observed Serum Concentration (Cmax) of JNJ-75348780 [ Time Frame: Predose, 48 hours postdose (up to 2.7 years) ]
  Cmax is the maximum observed serum concentration of JNJ-75348780.
• Minimum Observed Serum Concentration (Cmin) of JNJ-75348780 [ Time Frame: Predose, 48 hours postdose (up to 2.7 years) ]
  Cmin is the minimum observed serum concentration of JNJ-75348780.
• Objective Response Rate (ORR) [ Time Frame: Up to 2.7 years ]
  ORR is defined as the percentage of participants who achieve a complete response (CR) and 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.
• Complete Response (CR) Rate [ Time Frame: Up to 2.7 years ]
  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.
• Time to Response (TTR) [ Time Frame: Up to 2.7 years ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to 2.7 years ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of JNJ-75348780 in Participants With Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)
• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Lymphoma, Non-Hodgkin
• Leukemia, Lymphocytic, Chronic, B-Cell

Intervention

Drug: JNJ-75348780

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

Study Arms

• 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.
  Intervention: Drug: JNJ-75348780
• Experimental: Part B: Cohort Expansion
  Participants will receive JNJ-75348780 at one of the putative RP2Ds determined in Part A.
  Intervention: Drug: JNJ-75348780

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 2, 2020): 120
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 21, 2023
• Estimated Primary Completion Date: May 11, 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Australia, China, France, Israel, Korea, Republic of, Spain, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT04540796
• Other Study ID Numbers: CR108882; 2020-001183-29 ( EudraCT Number ); 75348780LYM1001 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinicaltrials/ transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Responsible Party: Janssen Research & Development, LLC
• Study Sponsor: Janssen Research & Development, LLC
• Collaborators: Not Provided

Investigators

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

• PRS Account: Janssen Research & Development, LLC
• Verification Date: May 2022