JNJ-80948543 for Lymphoma and Leukemia

Recruiting at 37 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

167 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests JNJ-80948543, a new medicine that helps the immune system fight B-cell non-Hodgkin lymphoid malignancies. It works by connecting immune cells to cancer cells, aiding in their destruction. The study aims to find the best dose and schedule while monitoring safety and effectiveness over an extended period.

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.

What makes the drug JNJ-80948543 unique for treating lymphoma and leukemia?

JNJ-80948543 is a trispecific antibody that targets CD79b, CD20, and CD3, which allows it to engage T cells to attack cancer cells more effectively. This approach is novel because it can target multiple antigens on cancer cells, potentially overcoming resistance seen with other treatments that target only one or two antigens. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment JNJ-80948543 for Lymphoma and Leukemia?

Research on similar trispecific antibodies, like the CD3/CD19/CD20 trispecific antibody, shows they can effectively recruit T cells to target and kill cancer cells, suggesting potential for JNJ-80948543 in treating leukemia and lymphoma. ^{1 3 4 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

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]

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 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]

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]

Citations

1. United States 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. [2021]

2. China 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. [2022]

3. United States 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. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Rejuvenation of tumour-specific T cells through bispecific antibodies targeting PD-L1 on dendritic cells. [2022]

5. England 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. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. [2021]