Lymphoma, Non-Hodgkin
Conditions
Brief summary
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.
Interventions
DRUGJNJ-95566692
JNJ-95566692 will be administered subcutaneously.
DRUGJNJ-87801493
JNJ-87801493 will be administered subcutaneously.
DRUGloncastuximab tesirine
Loncastuximab tesirine will be administered intervenously.
DRUGLenalidomide
Lenalidomide will be administered orally.
DRUGRituximab
Rituximab will be administered intravenously and may be administered subcutaneously after the first administration.
DRUGGemcitabine
Gemcitabine will be administered intravenously.
DRUGOxaliplatin
Oxaliplatin will be administered intravenously.
DRUGCyclophosphamide
Cyclophosphamide will be administered intravenously.
DRUGDoxorubicin
Doxorubicin will be administered intravenously.
DRUGVincristine
Vincristine will be administered intravenously.
DRUGPrednisone
Prednisone will be administered orally.
DRUGPolatuzumab vedotin
Polatuzumab vedotin will be administered intravenously.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1 and 2: Number of Participants with Adverse Events (AEs) And Serious Adverse Events (SAEs) by Severity | Approximately 2 years and 8 months | 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. |
| Part 1: Number of Participants with Dose Limiting Toxicity (DLTs) | Approximately 2 years and 8 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Volume of Distribution (V/F) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G) | Approximately 2 years and 8 months | V/F for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported. |
| Number of Participants with Anti-JNJ-95566692 Antibodies in Arms A to G | Approximately 2 years and 8 months | Participants with presence of antibodies binding to JNJ-95566692 in arm A to G will be reported. |
| Number of Participants with Anti-JNJ-87801493 Antibodies in Arms B to G | Approximately 2 years and 8 months | Participants with presence of antibodies binding to JNJ-87801493 in arm B to G (as appropriate) will be reported. |
| 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 | Approximately 2 years and 8 months | 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. |
| 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 | Approximately 2 years and 8 months | Complete response (CR) is defined as a best response of CR as assessed by the investigator according to standard response criteria per Lugano. |
| 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 | Approximately 2 years and 8 months | 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. |
| 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 | Approximately 2 years and 8 months | 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. |
| Serum Concentration for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G) | Approximately 2 years and 8 months | Serum concentration for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be assessed using a validated assay method. |
| Area Under the Curve During a Dosing Interval (AUCtau) in JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G) | Approximately 2 years and 8 months | AUC tau is defined as area under the serum concentration-time curve during a dosing interval (tau). |
| Maximum Serum Concentration (Cmax) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G) | Approximately 2 years and 8 months | Cmax for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported. |
| Minimum Serum Concentration (Cmin) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G) | Approximately 2 years and 8 months | Cmin for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported. |
| Area Under the Curve (AUC[0-t]) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G) | Approximately 2 years and 8 months | AUC(0-t) for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported. |
| Time to Reach Cmax (Tmax) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G) | Approximately 2 years and 8 months | 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. |
| Half-life (t1/2) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G) | Approximately 2 years and 8 months | Half-life (t1/2) for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported. |
| Apparent Total Body Clearance (CL/F) for JNJ-95566692 (Arms A-G) And JNJ-87801493 (Arms B-G) | Approximately 2 years and 8 months | CL/F for JNJ-95566692 (Arms A-G) and JNJ-87801493 (Arms B-G), where applicable will be reported. |
Countries
Australia, Belgium, France, Spain, Turkey (Türkiye)
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed