About this trial

The purpose of this study is to determine the putative recommended Phase 2 doses (RP2Ds) and optimal dose schedule(s) for JNJ-95566692 as a single agent (Arm A) and in combination with JNJ-87801493 (Arm B) and for JNJ-95566692 with or without JNJ-87801493 with various standard of care (SOC) regimens (Arms C-G) in Part 1: Dose Escalation part of the study. Part 2: Dose Expansion part of the study will further characterize the safety.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

B-cell non-Hodgkin lymphoid malignancies (NHL) according to World Health Organization (WHO) 2022 and no other approved therapies available that would be more appropriate in the investigator's judgment. -Histologic documentation of the following large B-cell lymphomas: -diffuse large B-cell lymphoma not otherwise specified (NOS), -T-cell/histiocyte-rich large B-cell lymphoma, -diffuse large B-cell lymphoma/high grade B-cell lymphoma with MYC and BCL2 rearrangements, -large B-cell lymphoma with IRF4 rearrangement, -high grade B-cell lymphoma with 11q aberrations, -Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma, -diffuse large B-cell lymphoma associated with chronic inflammation, -primary large B-cell lymphoma of immune privileged sites, -primary cutaneous diffuse large B-cell lymphoma-leg type , -primary mediastinal large B-cell lymphoma, -high-grade B-cell lymphoma NOS, -transformations of indolent B-cell lymphoma (For US sites). -Other B-cell NHL may be enrolled based on emerging data in specific cohorts as stipulated by study evaluation team (SET)

Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Participants must have measurable disease as defined by the disease criteria (Lugano criteria)

While on study treatment and for 3 months after the last dose of study treatment, a participant must: not breastfeed or become pregnant; not donate gametes (that is, eggs or sperm) or freeze for future use for the purposes of assisted reproduction; and wear an external condom; -Participants of childbearing potential must have a negative highly sensitive (for example, beta [β]-human chorionic gonadotropin) pregnancy test at screening and within 24 hours before the first dose of study treatment and agree to further pregnancy tests, -For Arm E ONLY: Practice 2 methods of reliable birth control simultaneously, including 1 highly effective form of contraception and 1 additional effective contraceptive method., -Participants on Arms C-G should also follow the pregnancy and contraception restrictions in the respective local corresponding product label

Disqualifiers

Known active central nervous system involvement (CNS) or leptomeningeal involvement

Prior solid-organ transplantation

Malignancy diagnosis other than the disease under study within 1 year prior to the first dose of the study treatment; 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 treatment in the opinion of both the investigator and sponsor's medical monitor

Autoimmune or inflammatory disease requiring systemic steroids or other immunosuppressive agents (for example, methotrexate or tacrolimus) within 3 months prior to first dose of study treatment

Trial design

Design model

Sequential

Treatments tested in this trial

JNJ-95566692
Drug
JNJ-95566692 will be administered subcutaneously.
JNJ-87801493
Drug
JNJ-87801493 will be administered subcutaneously.
loncastuximab tesirine
Drug
Loncastuximab tesirine will be administered intervenously.
Lenalidomide
Drug
Lenalidomide will be administered orally.
Rituximab
Drug
Rituximab will be administered intravenously and may be administered subcutaneously after the first administration.
Gemcitabine
Drug
Gemcitabine will be administered intravenously.
Oxaliplatin
Drug
Oxaliplatin will be administered intravenously.
Cyclophosphamide
Drug
Cyclophosphamide will be administered intravenously.
Doxorubicin
Drug
Doxorubicin will be administered intravenously.
Vincristine
Drug
Vincristine will be administered intravenously.
Prednisone
Drug
Prednisone will be administered orally.
Polatuzumab vedotin
Drug
Polatuzumab vedotin will be administered intravenously.

Treatment groups

340 Participants

are divided into 7 treatment groups

7

Treatment groups

See each treatment group below.

Group A: Arm A: JNJ-95566692Experimental treatment 1 intervention

Group B: Arm B: JNJ-95566692 in combination with JNJ-87801493Experimental treatment 2 interventions

Group C: Arm C: JNJ-95566692 and loncastuximab tesirine with or without JNJ-87801493Experimental treatment 3 interventions

Group D: Arm D: JNJ-95566692 and R-GemOx with or without JNJ-87801493Experimental treatment 5 interventions

Group E: Arm E: JNJ-95566692 and lenalidomide with or without JNJ-87801493Experimental treatment 3 interventions

Group F: Arm F: JNJ-95566692 and R-CHOP with or without JNJ-87801493Experimental treatment 7 interventions

Group G: Arm G: JNJ-95566692 and Pola-R-CHP with or without JNJ-87801493Experimental treatment 7 interventions

Trial outcomes

Primary outcomes

1

Part 1 and 2: Number of Participants with Adverse Events (AEs) And Serious Adverse Events (SAEs) 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: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grades which are Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (potentially life-threatening) and Grade 5 (death related to adverse event). SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.

Time frame