A Study of JNJ-95566692 in Participants With Non-Hodgkin Lymphoid Malignancies

A Phase 1, First-in-Human Study of a Novel CD79bxCD20xCD3 Trispecific Antibody in B-Cell Non-Hodgkin Lymphoid Malignancies (NHLs)

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.

Study Overview

• Status: Recruiting
• Conditions: Lymphoma, Non-Hodgkin
• Intervention / Treatment: Drug: Lenalidomide; Drug: Cyclophosphamide; Drug: Prednisone; Drug: JNJ-87801493; Drug: JNJ-95566692; Drug: loncastuximab tesirine; Drug: Rituximab; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Doxorubicin; Drug: Vincristine; Drug: Polatuzumab vedotin

• Study Type: Interventional
• Enrollment (Estimated): 340
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study1@its.jnj.com

Study Locations

• Australia
  • Clayton, Australia, 3168
    • Recruiting
    • Monash Medical Centre
  • Melbourne, Australia, 3000
    • Recruiting
    • Peter Maccallum Cancer Centre
  • North Ryde, Australia, 2109
    • Recruiting
    • Macquarie University Hospital
  • Randwick, Australia, 2031
    • Recruiting
    • Scientia Clinical Research
• Belgium
  • Edegem, Belgium, 2650
    • Recruiting
    • UZ Antwerpen
  • Liège, Belgium, 4000
    • Recruiting
    • Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
• France
  • Lille, France, 59000
    • Recruiting
    • Hôpital Claude Huriez
  • Paris, France, 75013
    • Recruiting
    • CHU Pitie Salpetriere
  • Pierre-Bénite, France, 69495
    • Recruiting
    • CHU Lyon Sud
  • Toulouse, France, 31100
    • Recruiting
    • Institut Universitaire du Cancer Toulouse Oncopole
• Spain
  • Barcelona, Spain, 8036
    • Recruiting
    • Hosp. Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Recruiting
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28041
    • Recruiting
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • Hosp Univ Fund Jimenez Diaz
  • Madrid, Spain, 28050
    • Recruiting
    • Hosp Univ Hm Sanchinarro
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06200
    • Recruiting
    • SBU Ankara Dr. Abdurrahman Yurtaslan Onkoloji Egitim ve Arastirma Hastanesi Faz 1 Merkezi
  • Ankara, Turkey (Türkiye), 06620
    • Recruiting
    • Ankara Universitesi Hastaneleri Tibbi Farmakoloji Anabilim Dali Faz 1 Klinik Arastirma Merkezi
  • Antalya, Turkey (Türkiye), 07025
    • Recruiting
    • Memorial Antalya Hastanesi Faz 1 Klinik Arastirma Merkezi
  • Istanbul, Turkey (Türkiye), 34010
    • Recruiting
    • Koc Universitesi Hastanesi Faz 1 Klinik Arastirma Merkezi

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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
• Toxicity from prior anticancer therapy that has not resolved to baseline levels or to Grade less than or equal to (<=) 1 (except alopecia, vitiligo, peripheral neuropathy, or Grade <=2 endocrinopathies that are stable on hormone replacement)

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

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: JNJ-95566692; Participants will receive escalating doses of JNJ-95566692 in Part 1 (Dose escalation) to determine the putative recommended Phase 2 doses (RP2D[s]) and dosing schedule(s). Participants in Part 2 (Dose expansion) will receive JNJ-95566692 at the putative RP2D(s) determined in Part 1 to further characterize safety, PK (pharmacokinetic), pharmacodynamic (PD) and clinical activity.	Drug: JNJ-95566692; JNJ-95566692 will be administered subcutaneously.
Experimental: Arm B: JNJ-95566692 in combination with JNJ-87801493; Participants will receive escalating doses of JNJ-95566692 in combination with JNJ-87801493 in Part 1 (Dose escalation) to determine the putative RP2D[s] and dosing schedule(s). Participants in Part 2 (Dose expansion) will receive JNJ-95566692 in combination with JNJ-87801493 at the putative RP2D(s) determined in Part 1 to further characterize safety, PK, PD and clinical activity.	Drug: JNJ-87801493; JNJ-87801493 will be administered subcutaneously.; Drug: JNJ-95566692; JNJ-95566692 will be administered subcutaneously.
Experimental: Arm C: JNJ-95566692 and loncastuximab tesirine with or without JNJ-87801493; Participants will receive escalating doses for JNJ-95566692 and loncastuximab tesirine with or without JNJ-87801493 followed by the target dose in Part 1 (Dose escalation) to determine the putative RP2D[s] and dosing schedule(s). Participants in Part 2 (Dose expansion) will receive JNJ-95566692 and loncastuximab tesirine with or without JNJ-87801493 at the putative RP2D(s) determined in Part 1.	Drug: JNJ-87801493; JNJ-87801493 will be administered subcutaneously.; Drug: JNJ-95566692; JNJ-95566692 will be administered subcutaneously.; Drug: loncastuximab tesirine; Loncastuximab tesirine will be administered intervenously.
Experimental: Arm D: JNJ-95566692 and R-GemOx with or without JNJ-87801493; Participants will receive escalating doses of JNJ-95566692 and R-GemOx (rituximab, gemcitabine, oxaliplatin) with or without JNJ-87801493 followed by the target dose in Part 1 (Dose escalation) to determine the putative RP2D[s] and dosing schedule(s). Participants in Part 2 (Dose expansion) will receive JNJ-95566692 and R-GemOx with or without JNJ-87801493 at the putative RP2D(s) determined in Part 1.	Drug: JNJ-87801493; JNJ-87801493 will be administered subcutaneously.; Drug: JNJ-95566692; JNJ-95566692 will be administered subcutaneously.; Drug: Rituximab; Rituximab will be administered intravenously and may be administered subcutaneously after the first administration.; Drug: Gemcitabine; Gemcitabine will be administered intravenously.; Drug: Oxaliplatin; Oxaliplatin will be administered intravenously.
Experimental: Arm E: JNJ-95566692 and lenalidomide with or without JNJ-87801493; Participants will receive escalating doses of JNJ-95566692 and lenalidomide with or without JNJ-87801493 in Part 1 (Dose escalation) to determine the putative RP2D[s] and dosing schedule(s). Participants in Part 2 (Dose expansion) will receive JNJ-95566692 and lenalidomide with or without JNJ-87801493 at the putative RP2D(s) determined in Part 1.	Drug: Lenalidomide; Lenalidomide will be administered orally.; Drug: JNJ-87801493; JNJ-87801493 will be administered subcutaneously.; Drug: JNJ-95566692; JNJ-95566692 will be administered subcutaneously.
Experimental: Arm F: JNJ-95566692 and R-CHOP with or without JNJ-87801493; Participants will receive escalating doses of JNJ-95566692 and R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) with or without JNJ-87801493 followed by the target dose in Part 1 (Dose escalation) to determine the putative RP2D[s] and dosing schedule(s). Participants in Part 2 (Dose expansion) will receive JNJ-95566692 and R-CHOP with or without JNJ-87801493 at the putative RP2D(s) determined in Part 1.	Drug: Cyclophosphamide; Cyclophosphamide will be administered intravenously.; Drug: Prednisone; Prednisone will be administered orally.; Drug: JNJ-87801493; JNJ-87801493 will be administered subcutaneously.; Drug: JNJ-95566692; JNJ-95566692 will be administered subcutaneously.; Drug: Rituximab; Rituximab will be administered intravenously and may be administered subcutaneously after the first administration.; Drug: Doxorubicin; Doxorubicin will be administered intravenously.; Drug: Vincristine; Vincristine will be administered intravenously.
Experimental: Arm G: JNJ-95566692 and Pola-R-CHP with or without JNJ-87801493; Participants will receive escalating doses of JNJ-95566692 and Pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) with or without JNJ-87801493 followed by the target dose in Part 1 (Dose escalation) to determine the putative RP2D[s] and dosing schedule(s). Participants in Part 2 (Dose expansion) will receive JNJ-95566692 and Pola-R-CHP with or without JNJ-87801493 at the putative RP2D(s) determined in Part 1.	Drug: Cyclophosphamide; Cyclophosphamide will be administered intravenously.; Drug: Prednisone; Prednisone will be administered orally.; Drug: JNJ-87801493; JNJ-87801493 will be administered subcutaneously.; Drug: JNJ-95566692; JNJ-95566692 will be administered subcutaneously.; Drug: Rituximab; Rituximab will be administered intravenously and may be administered subcutaneously after the first administration.; Drug: Doxorubicin; Doxorubicin will be administered intravenously.; Drug: Polatuzumab vedotin; Polatuzumab vedotin will be administered intravenously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Approximately 2 years and 8 months
Part 1: Number of Participants with Dose Limiting Toxicity (DLTs)	Number of participants with DLTs for JNJ-95566692 (arm A), in combination with JNJ-87801493 (arm B) and in arms C to G will be reported. The DLTs are drug-related toxicities and are defined as any of the following: fatal toxicity, high grade non-hematologic toxicity, or hematologic toxicity.	Approximately 2 years and 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Concentration for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G)	Serum concentration for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be assessed using a validated assay method.	Approximately 2 years and 8 months
Area Under the Curve During a Dosing Interval (AUCtau) in JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G)	AUC tau is defined as area under the serum concentration-time curve during a dosing interval (tau).	Approximately 2 years and 8 months
Maximum Serum Concentration (Cmax) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G)	Cmax for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.	Approximately 2 years and 8 months
Minimum Serum Concentration (Cmin) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G)	Cmin for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.	Approximately 2 years and 8 months
Area Under the Curve (AUC[0-t]) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G)	AUC(0-t) for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.	Approximately 2 years and 8 months
Half-life (t1/2) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G)	Half-life (t1/2) for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.	Approximately 2 years and 8 months
Time to Reach Cmax (Tmax) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G)	Tmax is the time to reach maximum observed serum concentration for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.	Approximately 2 years and 8 months
Apparent Total Body Clearance (CL/F) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G)	CL/F for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.	Approximately 2 years and 8 months
Apparent Volume of Distribution (V/F) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G)	V/F for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.	Approximately 2 years and 8 months
Number of Participants with Anti-JNJ-95566692 Antibodies in Arms A to G	Participants with presence of antibodies binding to JNJ-95566692 in arm A to G will be reported.	Approximately 2 years and 8 months
Number of Participants with Anti-JNJ-87801493 Antibodies in Arms B to G	Participants with presence of antibodies binding to JNJ-87801493 in arm B to G (as appropriate) will be reported.	Approximately 2 years and 8 months
Part 2: Overall Response for JNJ-95566692 (Arm A), in Combination With JNJ-87801493 (Arm B) And for JNJ-95566692 ± JNJ-87801493 with Combination Therapies In Arms C to G	Overall response is defined as a best response of partial response (PR) or better as assessed by the investigator according to standard response criteria per Lugano.	Approximately 2 years and 8 months
Part 2: Complete Response (CR) for JNJ-95566692 (Arm A), in Combination With JNJ-87801493 (Arm B) And for JNJ-95566692 ± JNJ-87801493 with Combination Therapies In Arms C to G	Complete response (CR) is defined as a best response of CR as assessed by the investigator according to standard response criteria per Lugano.	Approximately 2 years and 8 months
Part 2: Time to Response (TTR) for JNJ-95566692 (Arm A), in Combination With JNJ-87801493 (Arm B) And for JNJ-95566692 ± JNJ-87801493 with Combination Therapies In Arms C to G	TTR is defined for participants who achieved a response of PR or better as the time from the first dose of study treatment to the first response of PR or better.	Approximately 2 years and 8 months
Part 2: Duration of Response (DOR) for JNJ-95566692 (Arm A), in Combination With JNJ-87801493 (Arm B) And for JNJ-95566692 ± JNJ-87801493 with Combination Therapies In Arms C to G	DOR is defined for participants who achieved a response of PR or better as the time between the date of initial documentation of first response of PR or better to the date of first documented evidence of progressive disease, initiation of a new systemic anti-cancer therapy or death.	Approximately 2 years and 8 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): January 20, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): October 31, 2029

Study Registration Dates

• First Submitted: December 15, 2025
• First Submitted That Met QC Criteria: December 15, 2025
• First Posted (Actual): December 29, 2025

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 4, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Non-Hodgkin; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Carboxylic Acids; Alkaloids; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Piperidines; Indoles; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Anthracyclines; Naphthacenes; Aminoglycosides; Antibodies, Monoclonal, Murine-Derived; Daunorubicin; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; Oxaliplatin; Rituximab; Gemcitabine; Prednisone; Cyclophosphamide; Doxorubicin; Vincristine; polatuzumab vedotin; loncastuximab tesirine
• Other Study ID Numbers: 95566692LYM1001 (Other Identifier: Janssen Research & Development, LLC); 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk); 2025-523297-16-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of Johnson & Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes