JNJ-80948543 for Lymphoma and Leukemia

Not currently recruiting at 40 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must not be taking: Systemic steroids

Disqualifiers: CNS involvement, Organ transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, JNJ-80948543 (a trispecific antibody), for individuals with certain types of lymphoma and leukemia, such as non-Hodgkin lymphoma and chronic lymphocytic leukemia, who have not succeeded with other treatments. The main goal is to determine the safest and most effective dose and method of administration, either by injection under the skin or directly into a vein. It suits those whose disease has returned or not responded to at least two other treatments and who lack other treatment options. Participants will engage in two phases: one to determine the best dosage and another to confirm safety and effectiveness. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroids or other immunosuppressive agents, you may not be eligible to participate.

Is there any evidence suggesting that JNJ-80948543 is likely to be safe for humans?

Research has shown that JNJ-80948543 is under study for its safety in treating lymphoma and leukemia. This treatment is a trispecific antibody, targeting three different proteins on cancer cells to help the immune system attack them.

Since JNJ-80948543 remains in early clinical trials, detailed safety information is not yet fully available. However, these trials aim to determine the safest dose and the best method of administration. Researchers closely monitor for any side effects or adverse reactions.

Early trials like this primarily focus on ensuring safety. While some risks may exist, the goal is to find a well-tolerated treatment. For questions or concerns, consulting a doctor can help determine if this trial might be suitable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy options for lymphoma and leukemia, JNJ-80948543 is unique because it can be administered both subcutaneously and intravenously, offering flexibility in treatment delivery. Researchers are particularly excited about its innovative mechanism of action, targeting specific pathways that might lead to better outcomes and potentially fewer side effects compared to traditional treatments. This could pave the way for a more tailored and effective approach to treating these types of cancers.

What evidence suggests that JNJ-80948543 might be an effective treatment for lymphoma and leukemia?

Research has shown that JNJ-80948543 could be a promising treatment for certain blood cancers, such as lymphoma and leukemia. This trial will evaluate JNJ-80948543, a special type of antibody targeting specific proteins on cancer cells, CD79b and CD20, and a protein on T-cells, CD3. This targeting helps the immune system find and attack cancer cells more effectively. Early studies demonstrated that this approach can shrink tumors in some patients. While researchers are still collecting full results, these initial findings suggest potential benefits for people with these types of cancers. ^{1 2 3 5 6}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for adults with B-cell non-Hodgkin lymphoma or chronic lymphocytic leukemia who need treatment and have tried other therapies without success. They should be in good physical condition (ECOG Grade 0 or 1) and not pregnant, breastfeeding, or planning pregnancy soon. People with active brain involvement by cancer, recent organ transplants, autoimmune diseases needing strong medication within the last year, unresolved side effects from previous treatments (except certain stable conditions), or significant lung problems are excluded.

Inclusion Criteria

My lymphoma meets specific criteria for the trial.

I am a woman who can have children, not pregnant, and agree to regular pregnancy tests.

I am fully active or can carry out light work.

Exclusion Criteria

My cancer has spread to my brain or spinal cord.

I haven't taken steroids or immunosuppressants for my autoimmune disease in the last year.

I need extra oxygen to breathe properly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive JNJ-80948543 to determine the recommended Phase 2 dose, dosing schedule, and route of administration based on safety and preliminary efficacy

Up to 4 Years 3 months

Cohort Expansion

Participants receive JNJ-80948543 at the recommended Phase 2 dose to further characterize safety

Up to 4 Years 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• JNJ-80948543

Trial Overview

The study tests JNJ-80948543, a new type of antibody designed to target cancer cells in two phases: first to find the safest dose (Part A) and then to confirm its safety at that dose in more people (Part B). It's given to patients whose disease has returned after treatment or hasn't responded well to existing options.

How Is the Trial Designed?

Group I: Part B: Cohort Expansion Experimental Treatment 1 Intervention

Participants will receive JNJ-80948543 by SC or IV administration.

Group II: Part A: Dose Escalation Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

Blinatumomab, a bispecific T-cell engager, is effective for treating relapsed/refractory B-cell precursor acute lymphoblastic leukemia, but its short plasma half-life and the emergence of CD19-negative leukemic cells limit its clinical use.

The newly developed antibodies A-319 and A-2019 show strong antitumor activity, with A-319 being more effective against tumors, while A-2019 can target CD20 in cases where CD19 is absent, providing a potential treatment option for resistant leukemic cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical characterization and comparison between CD3/CD19 bispecific and novel CD3/CD19/CD20 trispecific antibodies against B-cell acute lymphoblastic leukemia: targeted immunotherapy for acute lymphoblastic leukemia. Wang, S., Peng, L., Xu, W., et al.[2022]

The study developed innovative triplebodies that retarget natural killer (NK) cells against chronic lymphocytic leukemia (CLL) cells, showing superior effectiveness in killing tumor cells compared to traditional bispecific antibodies.

One specific triplebody, ULBP2-aCD19-aCD19, demonstrated significant in vivo activity in a mouse model, indicating its potential as a promising therapeutic option for CLL by effectively triggering NK cell functions against both CLL cell lines and primary tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mono- and dual-targeting triplebodies activate natural killer cells and have anti-tumor activity in vitro and in vivo against chronic lymphocytic leukemia. Vyas, M., Schneider, AC., Shatnyeva, O., et al.[2021]

A newly designed bispecific antibody targeting both CD3ε and PD-L1 showed enhanced antitumor immune responses in various tumor models compared to conventional bispecific T-cell engagers (BiTEs).

The mechanism of action involves rejuvenating CD8 T cells through blocking PD-L1 on dendritic cells, leading to more durable and effective T-cell responses, suggesting a promising approach for long-lasting cancer immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rejuvenation of tumour-specific T cells through bispecific antibodies targeting PD-L1 on dendritic cells. Liu, L., Chen, J., Bae, J., et al.[2022]

Anti-CD20 antibodies, such as rituximab, ofatumumab, and obinutuzumab, have significantly improved response rates and survival in patients with chronic lymphocytic leukemia when added to chemotherapy regimens.

Newer anti-CD20 antibodies like ocaratuzumab, veltuzumab, and ublituximab are currently being tested in clinical trials, potentially expanding treatment options and allowing for combinations with novel small molecule agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dancing partners at the ball: Rational selection of next generation anti-CD20 antibodies for combination therapy of chronic lymphocytic leukemia in the novel agents era. Butler, LA., Tam, CS., Seymour, JF.[2018]

The bispecific antibody CD20-TDB effectively targets and kills CD20-expressing B cells, including those from leukemia and lymphoma patients, showing strong activity in both laboratory and animal studies.

In cynomolgus monkeys, a single dose of 1 mg/kg of CD20-TDB significantly depleted B cells in the blood and lymphoid tissues, with pharmacokinetics comparable to traditional monoclonal antibodies, suggesting it could be a promising treatment for B cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sun, LL., Ellerman, D., Mathieu, M., et al.[2021]

The study developed trispecific antibodies that can engage T cells and target tumor cells, showing that certain combinations of T cell receptor (TCR) and accessory molecules can enhance T cell activation and tumor cell lysis.

Two groups of trispecific antibodies were identified: one group showed minimal cytotoxicity despite effective T cell activation, while another group demonstrated high cytotoxicity against tumor cells, suggesting that the signals required for T cell proliferation differ from those needed for effective tumor lysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trispecific F(ab')3 derivatives that use cooperative signaling via the TCR/CD3 complex and CD2 to activate and redirect resting cytotoxic T cells. Tutt, A., Stevenson, GT., Glennie, MJ.[2017]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05424822

A Study of JNJ-80948543, a T-cell Redirecting CD79b x ...

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 ...

2.

cancer.gov

cancer.gov/publications/dictionaries/cancer-drug/def/anti-cd79b-cd20-cd3-trispecific-antibody-jnj-80948543

anti-CD79b/CD20/CD3 trispecific antibody JNJ-80948543

Upon administration, anti-CD79b/CD20/CD3 trispecific antibody JNJ-80948543 targets and binds to CD79b- and/or CD20-expressing tumor B-cells and CD3 antigen on ...

3.

prod-globaltrialfinder.janssen.com

prod-globaltrialfinder.janssen.com/trial/cr109174

A Study of JNJ-80948543, a T-cell Redirecting CD79b x CD20 ...

A Study of JNJ-80948543, a T-cell Redirecting CD79b x CD20 x CD3 Trispecific Antibody, in Participants With Non-Hodgkin Lymphoma (NHL) and ...

4.

clinicaltrials.jnj.com

clinicaltrials.jnj.com/en/study-detail/NCT06660563?

J&J Study NCT06660563

A Study of JNJ-80948543 in Combination With Other CD3 T-Cell Engagers in Participants With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (R/R B-Cell NHL).

5.

isrctn.com

isrctn.com/ISRCTN10023611

A study of JNJ-80948543 in combination with other CD3 T- ...

A study of JNJ-80948543 in combination with other CD3 T-cell engagers in participants with relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-Cell NHL)

6.

isrctn.com

isrctn.com/pdf/10023611

A study of JNJ-80948543 in combination with other CD3 T- ...

A T-cell redirecting trispecific (CD79b x CD20 x CD3) antibody is a novel treatment for patients with B- cell malignancies developed by drug ...