Clinical trial NCT05424822: A Study of JNJ-80948543, a T-cell Redirecting CD79b x CD20 x CD3 Trispecific Antibody, in Participants With Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)
Official title: A Phase 1, First-in-human Study of JNJ-80948543, a T-cell Redirecting Antibody, in Participants With NHL and CLL
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin
Leukemia, Lymphocytic, Chronic, B-Cell
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-06-21
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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
* Cardiac parameters within the following range: corrected QT interval (QTc intervals corrected using Fridericia's formula \[QTcF\]) less than or equal to (\<=) 480 milliseconds based on the average of triplicate assessments performed no more than 5 (plus minus \[+-\] 3) minutes apart
* A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test (beta- human chorionic gonadotropin) at screening and must agree to further serum or urine pregnancy tests prior to the first dose, during the study and until 3 months after the last dose of study treatment
* A female participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study treatment

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

Primary outcomes:
measure: Number of Participants with Dose-limiting Toxicity (DLT)
timeFrame: Up to 4 Years 3 months
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to 4 Years 3 months
measure: Number of Participants with AE by Severity
timeFrame: Up to 4 Years 3 months
Secondary outcomes:
measure: Serum Concentration of JNJ-80948543
timeFrame: Up to 4 Years 3 months
measure: Number of Participants with Presence of Anti-Drug Antibodies of JNJ-80948543
timeFrame: Up to 4 Years 3 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 4 Years 3 months
measure: Complete Response (CR) Rate
timeFrame: Up to 4 Years 3 months
measure: Rate of VGPR or Better for Participants with Waldenstrom Macroglobulinemia (WM)
timeFrame: Up to 4 Years 3 months
measure: Time to Response (TTR)
timeFrame: Up to 4 Years 3 months
measure: Duration of Response (DOR)
timeFrame: Up to 4 Years 3 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Macquarie University
country: Australia
facility: Macquarie University Hospital
city: Melbourne
country: Australia
facility: The Alfred Hospital
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
city: Randwick
country: Australia
facility: Scientia Clinical Research
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
city: Tianjin
country: China
facility: Tianjin cancer hospital
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College of Huazhong University of Science and Technology
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense University Hospital
city: Lille Cedex
country: France
facility: CHRU de Lille Hopital Claude Huriez
city: Paris
country: France
facility: Institut Curie
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe ICANS
city: Toulouse Cedex 9
country: France
facility: Institut Universitaire du cancer de Toulouse-Oncopole
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Nagoya Shi
country: Japan
facility: Aichi Cancer Center
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
city: Skorzewo
country: Poland
facility: Aidport Sp z o o
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: