Lymphoma, Non-Hodgkin

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.

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

Lymphoma, B-Cell

Lymphoma, Mantle-Cell

Mantle Cell Lymphoma

Lymphoma

Blood Cancer

Hematologic Neoplasms

Hematologic Malignancies

Hematology

Hematological Malignancies

Lenalidomide

Prednisone

Gemcitabine

Rituximab

Vincristine

Doxorubicin

Cyclophosphamide

Oxaliplatin

JNJ-87801493

JNJ-95566692

loncastuximab tesirine

Polatuzumab vedotin

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

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.

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.

Serum concentration for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be assessed using a validated assay method.

AUC tau is defined as area under the serum concentration-time curve during a dosing interval (tau).

Cmax for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.

Cmin for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.

AUC(0-t) for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.

Half-life (t1/2) for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.

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.

CL/F for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.

V/F for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported.

Participants with presence of antibodies binding to JNJ-95566692 in arm A to G will be reported.

Participants with presence of antibodies binding to JNJ-87801493 in arm B to G (as appropriate) will be reported.

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.

Complete response (CR) is defined as a best response of CR as assessed by the investigator according to standard response criteria per Lugano.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The purpose of this study is to determine the putative recommended Phase 2 doses (RP2Ds)
and optimal dose schedule(s) for JNJ-95566692 (Part 1: Dose Escalation) and to further
characterize the safety and clinical activity of JNJ-95566692 at the putative RP2D(s)
(Part 2: Dose Expansion).

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.

Number of participants with DLTs 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.

Serum concentration for JNJ-95566692 will be assessed using a validated assay method.

AUC tau is defined as area under the serum concentration-time curve during a dosing
interval (tau).

AUC[0-t] for JNJ-95566692 will be reported.

Half-life (t1/2) for JNJ-95566692 will be reported.

Tmax is the time to reach maximum observed serum concentration for JNJ-95566692.

Participants with presence of antibodies binding to JNJ-95566692 will be reported.

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.

Complete response (CR) is defined as a best response of CR as assessed by the
investigator according to standard response criteria per Lugano.

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.

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.

PFS is defined as the time from the date of first dose of study treatment to the date of
first documented evidence of progressive disease (as defined in the disease-specific
response criteria; unless) or death due to any cause, whichever occurs first.

Participants will receive escalating doses of JNJ-95566692 in Part 1 (Dose escalation) to
determine the putative recommended Phase 2 doses (RP2D[s]) and optimal 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), PD and clinical activity.

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

Trials at a glance

Trials at a glance

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

Outcome measures

Primary outcome measures

Secondary outcome measures