A Study of JNJ-87801493 in Combination With T-Cell Engagers in Participants With B-cell Non-Hodgkin Lymphoid (NHLs) Cancer

A Phase 1, First-in-human Study of JNJ-87801493 in Combination With CD3 T-Cell Engagers in Participants With Relapsed/Refractory B-cell Non-Hodgkin Lymphoid Malignancies (NHLs)

The purpose of this study is to characterize safety and to determine the recommended phase 2 regimen (RP2R) for JNJ-87801493 in combination with T-cell engagers (TCEs) [Part A: Dose Escalation] and to further assess the safety of JNJ-87801493 at the RP2R in combination with TCEs [Part B: Dose Expansion].

Study Overview

• Status: Recruiting
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Drug: JNJ-87801493; Drug: JNJ-80948543; Drug: JNJ-75348780

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Recruiting
    • Linear Clinical Research Ltd
  • Randwick, Australia, 2031
    • Recruiting
    • Scientia Clinical Research
• Denmark
  • Copenhagen, Denmark, DK-2100
    • Recruiting
    • Rigshospitalet
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
• Israel
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Sourasky (Ichilov) Medical Center
• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp. Univ. Fund. Jimenez Diaz
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Univ. de Navarra
  • Salamanca, Spain, 37007
    • Recruiting
    • Hosp. Clinico Univ. de Salamanca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologic documentation of B-cell NHL. All participants must have relapsed or refractory disease with no other approved therapies available that would be more appropriate in the investigator's judgment
• Part 1 and Part 2 participants must have either evaluable or measurable disease as defined by the appropriate disease response criteria
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Hematologic laboratory parameters must meet the required criterias and the values must be without a transfusion or growth factors for at least 7 days prior to the first dose of study drug
• Participants of childbearing potential must have a negative highly sensitive serum pregnancy test (beta (β)-human chorionic gonadotropin) at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.

Exclusion Criteria:

• Known active central nervous system involvement (CNS) or leptomeningeal involvement. CNS involvement may be allowed in specific cohorts as determined by the Study Evaluation Team (SET)
• Prior solid-organ transplantation
• Prior treatment with JNJ-80948543 and/or JNJ-75348780
• Chemotherapy, targeted therapy, or immunotherapy within 14 days before the first dose of study treatment
• Malignancy diagnosis other than the disease under study within 1 year prior to screening. Exceptions are squamous and basal cell carcinoma of the skin, carcinoma in situ of the cervix and any malignancy that is considered cured or has minimal risk of recurrence within 1 year of first dose of the study drugs in the opinion of both the investigator and sponsor's medical monitor
• Autoimmune or inflammatory disease requiring systemic corticosteroids or other immunosuppressive agents within 1 year prior to first dose of study treatment
• Evidence of active viral, bacterial, or uncontrolled systemic fungal infection requiring systemic treatment within 7 days before the first dose of study treatment
• Abnormal cardiac function

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose escalation; Participants will receive one cycle of TCE monotherapy (step up to target dose) with either JNJ-80948543 or JNJ-75348780 followed by initiation of combination therapy with JNJ-87801493 one week later.	Drug: JNJ-87801493; JNJ-87801493 will be administered subcutaneously.; Drug: JNJ-80948543; JNJ-80948543 will be administered subcutaneously.; Drug: JNJ-75348780; JNJ-75348780 will be administered subcutaneously.
Experimental: Part 2:Dose expansion; Participants with specific B-cell NHL histologies will receive recommended phase 2 regimen (RP2R) of JNJ-87801493 with TCE as determined in Part 1.	Drug: JNJ-87801493; JNJ-87801493 will be administered subcutaneously.; Drug: JNJ-80948543; JNJ-80948543 will be administered subcutaneously.; Drug: JNJ-75348780; JNJ-75348780 will be administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants with Dose Limiting Toxicity (DLTs)	Number of participants with DLTs will be reported. The DLTs are specific adverse events and are defined as any of the following: fatal toxicity, high grade non-hematologic toxicity, or hematologic toxicity	Up to 2 years 7 months
Part 1 and 2: Percentage of Participants with Adverse Events (AEs) by Severity	An AE is any untoward medical occurrence in a clinical study participant administered an investigational or non-investigational product and it does not necessarily have a causal relationship with the investigational product. Severity for AEs will be specified as per: NCI-CTCAE grades which are Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (potentially life-threatening) and; American Society for Transplantation and Cellular Therapy (ASTCT) guidelines which is Grade 5 (death related to adverse event) Cytokine release syndrome (CRS) and associated neurologic toxicity events (immune effector cell-associated neurotoxicity syndrome events [ICANS]).	Up to 2 years 7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response as Assessed by the Investigator	Overall response is defined as a best response of partial response (PR) or better.	Up to 2 years 7 months
Complete Response (CR) as Assessed by the Investigator	Complete response (CR) is defined as a best response of CR.	Up to 2 years 7 months
Very Good Partial Response (VGPR) or better for Waldenström Macroglobulinemia (WM) Participants as Assessed by the Investigator	Very good partial response (VGPR) is defined as a best response of VGPR or better.	Up to 2 years 7 months
Time to Response (TTR) as Assessed by the Investigator	Time to response (TTR) is defined for participants who achieve a response of PR or better as the time from the first dose of any study drug to the first response of PR or better.	Up to 2 years 7 months
Duration of Response (DOR) as Assessed by the Investigator	Duration of response (DOR) is defined for participants who achieved a response of PR or better as the time from the first efficacy evaluation at which the participant meet all criteria for a response of PR or better to the date of first documented evidence of progressive disease or death.	Up to 2 years 7 months
Serum Concentration for JNJ-87801493, JNJ-80948543 and JNJ-75348780	Serum Concentration for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.	Up to 2 years 7 months
Area Under the Curve (AUCtau) for JNJ-87801493, JNJ-80948543 and JNJ-75348780	AUC tau is defined as area under the serum concentration-time curve during a dosing interval (tau).Area under the serum concentration curve (AUCtau) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.	Up to 2 years 7 months
Maximum Serum Concentration (Cmax) for JNJ-87801493, JNJ-80948543 and JNJ-75348780	Maximum observed serum concentration (Cmax) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.	Up to 2 years 7 months
Minimum Serum Concentration (Cmin) for JNJ-87801493, JNJ-80948543 and JNJ-75348780	Minimum observed serum concentration (Cmin) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.	Up to 2 years 7 months
Area Under the Curve (AUC[0-t]) for JNJ-87801493, JNJ-80948543 and JNJ-75348780	Area under the curve from time zero to t (AUC[0-t]) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.	Up to 2 years 7 months
Half-life (t1/2) for JNJ-87801493, JNJ-80948543 and JNJ-75348780	Half-life (t1/2) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.	Up to 2 years 7 months
Time to Reach Cmax (Tmax) for JNJ-87801493, JNJ-80948543 and JNJ-75348780	Tmax is the time to reach maximum observed serum concentartion for JNJ-87801493, JNJ-80948543 and JNJ-75348780.	Up to 2 years 7 months
Apparent Total Body Clearance (CL/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780	Apparent total body clearance (CL/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.	Up to 2 years 7 months
Apparent Volume of Distribution (V/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780	Apparent volume of distribution (V/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.	Up to 2 years 7 months
Number of Participants with Presence of Anti-JNJ-87801493, Anti-JNJ- 80948543 and Anti-JNJ-75348780 Antibodies	Number of participants with presence of antibodies binding to JNJ-87801493 or each combination partner (JNJ- 80948543 and JNJ-75348780).	Up to 2 years 7 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2023
• Primary Completion (Estimated): July 8, 2026
• Study Completion (Estimated): July 8, 2026

Study Registration Dates

• First Submitted: November 15, 2023
• First Submitted That Met QC Criteria: November 15, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: 87801493LYM1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical-trials/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

Drug and device information, study documents

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