A Phase 1, First-in-human Study of JNJ-80948543, a T-cell Redirecting Antibody, in Participants With NHL and CLL
Overview
- Phase
- Phase 1
- Intervention
- JNJ-80948543
- Conditions
- Lymphoma, Non-Hodgkin
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 167
- Locations
- 51
- Primary Endpoint
- Number of Participants with Dose-limiting Toxicity (DLT)
- Status
- Active, not recruiting
- Last Updated
- 19 days ago
Overview
Brief Summary
The purpose of this study is to characterize safety and to determine the putative recommended Phase 2 dose(s) (RP2D[s]), optimal dosing schedule(s) and route(s) of administration of JNJ-80948543 in Part A (Dose Escalation) and to further characterize the safety of JNJ-80948543 at the putative RP2D(s) in Part B (Cohort Expansion).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologic documentation of disease: B-cell non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) requiring therapy.
- •All participants must have relapsed or refractory disease with no other approved therapies available that would be more appropriate in the investigator's judgment.
- •B-cell NHL as defined per the 2016 world health organization (WHO) classification. In addition, the following disease-specific criteria outlined below must be met:
- •If diffuse large B-cell lymphoma (DLBCL) or other high-Grade B-cell lymphoma: Received, or not eligible for high-dose chemotherapy and autologous stem cell transplantation with curative intent or deemed not eligible or fit for an alternative 2nd line therapy. Participants may be eligible if relapsing after chimeric antigen receptors (CAR-T) cell treatment or while waiting for a CAR-T cell treatment.
- •If transformed lymphoma from low Grade B-cell malignancies: Received or not a candidate for an approved first-line regimen for DLBCL and received or not eligible for high-dose chemotherapy and autologous stem cell transplantation with curative intent.
- •If follicular lymphoma (FL) (all grades): Previously treated with a minimum of 2 prior lines of systemic therapy, with at least one prior line containing an anti-CD20 antibody.
- •If mantle cell lymphoma (MCL), marginal zone lymphoma (MZL) (including nodal, extranodal/MALT, and splenic MZL subtypes): Previously treated with at least 2 lines of systemic therapy. H.pylori-positive gastric MALT lymphoma must have failed prior H. pylori eradication therapy as one of their prior lines .
- •Waldenstrom macroglobulinemia (WM): Previously treated with at least 1 line of systemic therapy.
- •small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL/SLL): Relapsed or refractory with at least 2 prior lines of therapy, including a Bruton tyrosine kinase inhibitor (BTK) inhibitor or a BCL2 inhibitor, if eligible. In addition for part B Participants must have measurable disease as defined by the appropriate disease response criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status Grade of 0 or 1
Exclusion Criteria
- •Known active central nervous system (CNS) involvement; Lymphoma with CNS involvement may be allowed in pharmacokinetic/ pharmacodynamic (PK/PD) and expansion cohorts if approved by the study evaluation team (SET)
- •Prior solid-organ transplantation
- •Autoimmune or inflammatory disease requiring systemic steroids or other immunosuppressive agents (example, methotrexate or tacrolimus) within 1 year prior to first dose of study drug
- •Toxicity from prior anticancer therapy has not resolved to baseline levels or to Grade \<= 1 (except alopecia, vitiligo, peripheral neuropathy, or endocrinopathies that are stable on hormone replacement, which may be Grade 2)
- •Clinically significant pulmonary compromise, particularly the need for supplemental oxygen use to maintain adequate oxygenation
Arms & Interventions
Part B: Cohort Expansion
Participants will receive JNJ-80948543 by SC or IV administration.
Intervention: JNJ-80948543
Part A: Dose Escalation
Participants will receive JNJ-80948543 either by subcutaneous (SC) or intravenous (IV) administration to determine the putative recommended Phase 2 dose (RP2D) dosing schedule(s) and route(s) of administration based on safety, pharmacokinetic, pharmacodynamic, and preliminary assessment of efficacy across several dose regimens.
Intervention: JNJ-80948543
Outcomes
Primary Outcomes
Number of Participants with Dose-limiting Toxicity (DLT)
Time Frame: Up to 4 Years 3 months
Number of participants with DLT will be reported. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Number of Participants with AE by Severity
Time Frame: Up to 4 Years 3 months
Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Severity scale ranges from Grade 1 (Mild) to Grade 4 (Life-threatening). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) will be graded as per American Society for Transplantation and Cellular Therapy (ASTCT).
Number of Participants with Adverse Events (AEs)
Time Frame: Up to 4 Years 3 months
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.
Secondary Outcomes
- Serum Concentration of JNJ-80948543(Up to 4 Years 3 months)
- Number of Participants with Presence of Anti-Drug Antibodies of JNJ-80948543(Up to 4 Years 3 months)
- Overall Response Rate (ORR)(Up to 4 Years 3 months)
- Rate of VGPR or Better for Participants with Waldenstrom Macroglobulinemia (WM)(Up to 4 Years 3 months)
- Duration of Response (DOR)(Up to 4 Years 3 months)
- Complete Response (CR) Rate(Up to 4 Years 3 months)
- Time to Response (TTR)(Up to 4 Years 3 months)