A Study of JNJ-87801493 in Combination With T-Cell Engagers in Participants With B-cell Non-Hodgkin Lymphoid (NHLs) Cancer
Study Details
Study Description
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].
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part 1: Dose escalation Participants will receive one cycle of TCE monotherapy (step up to target dose) with either JNJ-80948543 or JNJ-75348780 followed by initiation of combination therapy with JNJ-87801493 one week later. |
Drug: JNJ-87801493
JNJ-87801493 will be administered subcutaneously.
Drug: JNJ-80948543
JNJ-80948543 will be administered subcutaneously.
Drug: JNJ-75348780
JNJ-75348780 will be administered subcutaneously.
|
| Experimental: Part 2:Dose expansion Participants with specific B-cell NHL histologies will receive recommended phase 2 regimen (RP2R) of JNJ-87801493 with TCE as determined in Part 1. |
Drug: JNJ-87801493
JNJ-87801493 will be administered subcutaneously.
Drug: JNJ-80948543
JNJ-80948543 will be administered subcutaneously.
Drug: JNJ-75348780
JNJ-75348780 will be administered subcutaneously.
|
Outcome Measures
Primary Outcome Measures
- Part 1: Number of Participants with Dose Limiting Toxicity (DLTs) [Up to 2 years 7 months]
Number of participants with DLTs will be reported. The DLTs are specific adverse events and are defined as any of the following: fatal toxicity, high grade non-hematologic toxicity, or hematologic toxicity
- Part 1 and 2: Percentage of Participants with Adverse Events (AEs) by Severity [Up to 2 years 7 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: NCI-CTCAE grades which are Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (potentially life-threatening) and; American Society for Transplantation and Cellular Therapy (ASTCT) guidelines which is Grade 5 (death related to adverse event) Cytokine release syndrome (CRS) and associated neurologic toxicity events (immune effector cell-associated neurotoxicity syndrome events [ICANS]).
Secondary Outcome Measures
- Serum Concentration for JNJ-87801493, JNJ-80948543 and JNJ-75348780 [Pre-dose, up to 168 hours post dose on Day 1]
Serum Concentration for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.
- Area Under the Curve (AUCtau) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 [Pre-dose, up to 168 hours post dose on Day 1]
AUC tau is defined as area under the serum concentration-time curve during a dosing interval (tau).Area under the serum concentration curve (AUCtau) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.
- Maximum Serum Concentration (Cmax) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 [Pre-dose, up to 168 hours post dose on Day 1]
Maximum observed serum concentration (Cmax) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.
- Minimum Serum Concentration (Cmin) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 [Pre-dose, up to 168 hours post dose on Day 1]
Minimum observed serum concentration (Cmin) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.
- Area Under the Curve (AUC[0-t]) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 [Pre-dose, up to 168 hours post dose on Day 1]
Area under the curve from time zero to t (AUC[0-t]) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.
- Half-life (t1/2) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 [Pre-dose, up to 168 hours post dose on Day 1]
Half-life (t1/2) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.
- Time to Reach Cmax (Tmax) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 [Pre-dose, up to 168 hours post dose on Day 1]
Tmax is the time to reach maximum observed serum concentartion for JNJ-87801493, JNJ-80948543 and JNJ-75348780.
- Apparent Total Body Clearance (CL/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 [Pre-dose, up to 168 hours post dose on Day 1]
Apparent total body clearance (CL/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.
- Apparent Volume of Distribution (V/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 [Pre-dose, up to 168 hours post dose on Day 1]
Apparent volume of distribution (V/F) for JNJ-87801493, JNJ-80948543 and JNJ-75348780 will be reported.
- Number of Participants with Presence of Anti-JNJ-87801493, Anti-JNJ- 80948543 and Anti-JNJ-75348780 Antibodies [Pre-dose, up to 168 hours post dose on Day 1]
Number of participants with presence of antibodies binding to JNJ-87801493 or each combination partner (JNJ- 80948543 and JNJ-75348780).
- Overall Response as Assessed by the Investigator [Up to 2 years 7 months]
Overall response is defined as a best response of partial response (PR) or better.
- Complete Response (CR) as Assessed by the Investigator [Up to 2 years 7 months]
Complete response (CR) is defined as a best response of CR.
- Very Good Partial Response (VGPR) or better for Waldenström Macroglobulinemia (WM) Participants as Assessed by the Investigator [Up to 2 years 7 months]
Very good partial response (VGPR) is defined as a best response of VGPR or better.
- Time to Response (TTR) as Assessed by the Investigator [Up to 2 years 7 months]
Time to response (TTR) is defined for participants who achieve a response of PR or better as the time from the first dose of any study drug to the first response of PR or better.
- Duration of Response (DOR) as Assessed by the Investigator [Up to 2 years 7 months]
Duration of response (DOR) is defined for participants who achieved a response of PR or better as the time from the first efficacy evaluation at which the participant meet all criteria for a response of PR or better to the date of first documented evidence of progressive disease or death.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Histologic documentation of B-cell NHL. All participants must have relapsed or refractory disease with no other approved therapies available that would be more appropriate in the investigator's judgment
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Part 1 and Part 2 participants must have either evaluable or measurable disease as defined by the appropriate disease response criteria
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Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
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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
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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:
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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)
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Prior solid-organ transplantation
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Prior treatment with JNJ-80948543 and/or JNJ-75348780
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Chemotherapy, targeted therapy, or immunotherapy within 14 days before the first dose of study treatment
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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
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Autoimmune or inflammatory disease requiring systemic corticosteroids or other immunosuppressive agents within 1 year prior to first dose of study treatment
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Evidence of active viral, bacterial, or uncontrolled systemic fungal infection requiring systemic treatment within 7 days before the first dose of study treatment
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Abnormal cardiac function
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 87801493LYM1001