Clinical trial NCT06139406: A Study of JNJ-87801493 in Combination With T-Cell Engagers in Participants With B-cell Non-Hodgkin Lymphoid (NHLs) Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2023-11-18
Enrollment: 235
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 \[Part B: Dose Expansion\].


Eligibility criteria: Inclusion Criteria:

* Histologic documentation of B-cell NHL. All participants in part 1 must have relapsed or refractory disease with no other approved therapies available that would be more appropriate in the investigator's judgment. In Part 2, participants with diffuse large B-cell lymphoma (DLBCL) or other high-grade B cell lymphoma and participants with transformed lymphoma from low-grade B cell malignancies who relapsed or failed to respond to only one prior systemic treatment regimen can be included
* Part 1 participants must have evaluable or measurable disease and Part 2 participants must have measurable disease; all as defined by the Lugano criteria for non-Hodgkin lymphoid malignancies (NHL) and the international workshop on Waldenstrom's Macroglobulinemia (IWWM-6) for WM
* 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. In addition, history of known allergies, hypersensitivity, or intolerance to either JNJ-80948543, JNJ-75348780, or JNJ-87801493 or its excipients
* Chemotherapy, targeted therapy, or immunotherapy within 2 weeks before the first dose of study treatment. 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. For checkpoint blockade therapy (example, anti-programmed cell death protein-1 \[anti-PD-1\]), a washout period of up to 6 weeks may be considered
* 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

Primary outcomes:
measure: Part 1: Number of Participants with Dose Limiting Toxicity (DLTs)
timeFrame: Up to 2 years 7 months
measure: Part 1 and 2: Percentage of Participants with Adverse Events (AEs) by Severity
timeFrame: Up to 2 years 7 months
Secondary outcomes:
measure: Serum Concentration for JNJ-87801493, JNJ-80948543 and JNJ-75348780
timeFrame: Up to 2 years 7 months
measure: Area Under the Curve (AUCtau) for JNJ-87801493, JNJ-80948543 and JNJ-75348780
timeFrame: Up to 2 years 7 months
measure: Maximum Serum Concentration (Cmax) for JNJ-87801493, JNJ-80948543 and JNJ-75348780
timeFrame: Up to 2 years 7 months
measure: Minimum Serum Concentration (Cmin) for JNJ-87801493, JNJ-80948543 and JNJ-75348780
timeFrame: Up to 2 years 7 months
measure: Area Under the Curve (AUC[0-t]) for JNJ-87801493, JNJ-80948543 and JNJ-75348780
timeFrame: Up to 2 years 7 months
measure: Half-life (t1/2) for JNJ-87801493, JNJ-80948543 and JNJ-75348780
timeFrame: Up to 2 years 7 months
measure: Time to Reach Cmax (Tmax) for JNJ-87801493, JNJ-80948543 and JNJ-75348780
timeFrame: Up to 2 years 7 months
measure: Apparent Total Body Clearance (CL/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780
timeFrame: Up to 2 years 7 months
measure: Apparent Volume of Distribution (V/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780
timeFrame: Up to 2 years 7 months
measure: Number of Participants with Presence of Anti-JNJ-87801493, Anti-JNJ- 80948543 and Anti-JNJ-75348780 Antibodies
timeFrame: Up to 2 years 7 months
measure: Overall Response as Assessed by the Investigator
timeFrame: Up to 2 years 7 months
measure: Complete Response (CR) as Assessed by the Investigator
timeFrame: Up to 2 years 7 months
measure: Very Good Partial Response (VGPR) or better for Waldenström Macroglobulinemia (WM) Participants as Assessed by the Investigator
timeFrame: Up to 2 years 7 months
measure: Time to Response (TTR) as Assessed by the Investigator
timeFrame: Up to 2 years 7 months
measure: Duration of Response (DOR) as Assessed by the Investigator
timeFrame: Up to 2 years 7 months
Other outcomes:
Locations:
city: Heidelberg
country: Australia
facility: Austin Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
city: Randwick
country: Australia
facility: Scientia Clinical Research
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky (Ichilov) Medical Center
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: