CLN-978 for B-Cell Lymphoma

Not currently recruiting at 5 trial locations

Overseen By Maria Akhondzadeh

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cullinan Oncology, LLC

Must not be taking: CD19 antibodies, CAR-T

Disqualifiers: CNS lymphoma, Cardiac disease, Autoimmune, Infections, 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 called CLN-978 for individuals with certain types of B-cell lymphoma, a blood cancer affecting the lymphatic system. The study explores how different doses of CLN-978 work in patients whose cancer has returned or hasn't responded to at least two other treatments. Participants should have a type of B-cell lymphoma, such as diffuse large B-cell lymphoma or follicular lymphoma, and must have experienced a relapse or resistance to previous treatments. The goal is to find a safe and effective dose to help manage this challenging condition. As a Phase 1 trial, this research focuses on understanding how CLN-978 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like recent chemotherapy, monoclonal antibodies, or radiation therapy may need to be paused before starting the trial.

Is there any evidence suggesting that CLN-978 is likely to be safe for humans?

Research shows that CLN-978 is a new treatment under testing for B-cell lymphoma, a type of blood cancer. In early studies, CLN-978 has shown promise in attacking cancer cells without causing severe side effects.

Patients in previous trials handled CLN-978 well, experiencing side effects typical of treatments that activate the immune system. These side effects can include mild fever or tiredness, but serious issues have been rare.

Since this trial is in the early stages, the main goal is to learn more about the treatment's safety and determine the right dose. Researchers are closely monitoring the treatment to ensure it is safe for more people in the future. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for B-cell lymphoma, such as chemotherapy and monoclonal antibodies, CLN-978 is a bispecific T-cell engager. This means it can simultaneously bind to both cancer cells and T-cells, potentially enhancing the immune system's ability to target and destroy cancerous cells. Researchers are excited about CLN-978 because this dual-targeting approach offers a new mechanism that could lead to more precise and effective treatment options, especially for patients with relapsed or refractory forms of the disease. Additionally, the ability to adjust the dosage in a controlled manner during the trial might help optimize its safety and efficacy, offering hope for a more tailored treatment approach.

What evidence suggests that CLN-978 might be an effective treatment for B-cell lymphoma?

Research has shown that CLN-978 holds promise for treating B-cell Non-Hodgkin Lymphoma. Early studies found that CLN-978 can help the body's T cells locate and destroy cancer cells using a protein called CD19. It performed well in both lab and animal tests. This trial will evaluate CLN-978 in two parts: Part A involves dose escalation for patients with relapsed or refractory B-cell Non-Hodgkin Lymphoma, and Part B involves dose expansion for patients with relapsed or refractory diffuse large B-cell lymphoma, follicular lymphoma, and other B-cell Non-Hodgkin Lymphomas. Although more research is needed, these early results suggest it could be a strong new treatment option. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with B-cell Non-Hodgkin Lymphoma that has come back or didn't respond to treatment. They must have tried at least two prior therapies and be in fairly good physical shape (ECOG PS ≤ 2). People can't join if they've had certain recent treatments, like CAR-T therapy, organ transplants, or are pregnant. Also excluded are those with autoimmune diseases needing immune suppression, active infections including COVID-19, or significant heart disease.

Inclusion Criteria

Measurable disease defined as specific criteria on imaging

Laboratory parameters meeting specified ranges

I can take care of myself and perform daily activities.

Exclusion Criteria

I have a serious brain or spinal cord condition.

I have or had cancer types other than the one I'm seeking treatment for.

My lymphoma affects my brain or central nervous system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Patients with R/R B-NHL treated with CLN-978 in dose escalation cohorts

24 months

Dose Expansion

Patients with R/R DLBCL, R/R FL and other R/R B-NHL treated with CLN-978 at a dose selected from the Part A Dose Escalation arm

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• CLN-978

Trial Overview The study tests CLN-978 in patients whose B-NHL has relapsed or hasn't responded to other treatments. It's an early-phase trial where researchers first find the best dose of CLN-978 and then see how well it works on different types of this lymphoma.

How Is the Trial Designed?

Group I: Part B Dose Expansion Experimental Treatment 1 Intervention

Patients with R/R DLBCL, R/R FL and other R/R B-NHL treated with CLN-978 at a dose selected from the Part A Dose Escalation arm.

Group II: Part A Dose Escalation Experimental Treatment 1 Intervention

Patients with R/R B-NHL treated with CLN-978 in dose escalation cohorts

Who Is Running the Clinical Trial?

Cullinan Oncology, LLC

Lead Sponsor

Trials

7

Recruited

990+

Cullinan Therapeutics Inc.

Lead Sponsor

Trials

9

Recruited

1,000+

Cullinan Oncology Inc.

Lead Sponsor

Trials

6

Recruited

710+

Published Research Related to This Trial

Acalabrutinib, a Bruton's tyrosine kinase inhibitor, has been shown to be effective and safe for treating chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), with significant improvements in efficacy observed in both monotherapy and combination treatments.

In clinical studies, acalabrutinib demonstrated a high rate of molecular remission when combined with venetoclax, while maintaining an acceptable safety profile, although some adverse events occurred in over 20% of patients, including myelosuppression and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib and its use in the treatment of chronic lymphocytic leukemia. Egyed, M., Lueff, S., Borbely, J., et al.[2022]

Recent advancements in chronic lymphocytic leukemia (CLL) treatment, particularly with small molecule inhibitors, have shown significant clinical efficacy in both untreated and relapsed patients, but they also come with increased risks of specific adverse events.

An individualized treatment approach is now possible with targeted therapies like B-cell receptor inhibitors and venetoclax, emphasizing the need for a thorough understanding of their mechanisms, efficacy, and side effects to optimize patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimizing and managing treatment-associated complications in patients with chronic lymphocytic leukemia. Iskierka-Jażdżewska, E., Robak, T.[2021]

The combination therapy of obinutuzumab and ibrutinib, following a debulking phase with bendamustine, resulted in a 100% overall response rate in 61 patients with chronic lymphocytic leukemia (CLL), demonstrating its high efficacy.

The treatment was generally safe, with the most common severe side effects being neutropenia (14.8%) and thrombocytopenia (13.1%), and only one reported fatality, indicating a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CLL2-BIG: sequential treatment with bendamustine, ibrutinib and obinutuzumab (GA101) in chronic lymphocytic leukemia. von Tresckow, J., Cramer, P., Bahlo, J., et al.[2022]

New-generation Bruton tyrosine kinase inhibitors (BTKi) show a high overall response rate of 92% in treating chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), particularly benefiting younger patients and those receiving combination therapy.

While BTKi-based therapies are generally well-tolerated, they can lead to significant adverse events like cytopenia and hypertension, and zanubrutinib may offer better efficacy than acalabrutinib as a monotherapy for CLL/SLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of new-generation Bruton tyrosine kinase inhibitors in chronic lymphocytic leukemia/small lymphocytic lymphoma: a systematic review and meta-analysis. Yin, S., Zheng, X., Zhang, W., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05879744

A Study of CLN-978 in Patients With Relapsed or ... CLN-978-001 is a Phase 1, open-label, dose escalation and dose expansion study of CLN-978 in patients with Relapse/Refractory (R/R) B-cell Non-Hodgkin Lymphoma ...

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/3142/501375/A-Phase-1-Open-Label-Dose-Escalation-and-Dose

A Phase 1, Open-Label, Dose Escalation and Dose ... Preclinically, CLN-978 effectively redirects T cells to kill CD19-expressing malignant cells and has demonstrated potent in vitro and in vivo ...

3. targetedonc.com targetedonc.com/view/investigational-cln-978-therapy-starts-in-patients-with-r-r-b-cell-nhl

Investigational CLN-978 Therapy Starts in Patients with R ... Patients with relapsed or refractory B-cell non-Hodgkin lymphoma can receive the experimental chimeric antigen receptor T-cell therapy, CLN-978, in a clinical ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123097446

A Phase 1, Open-Label, Dose Escalation and ... Preclinically, CLN-978 effectively redirects T cells to kill CD19-expressing malignant cells and has demonstrated potent in vitro and in vivo ...

5. bloodcancerstoday.com bloodcancerstoday.com/post/novel-cln-978-elicited-potent-efficacy-against-b-cell-lymphoma-cells

Novel CLN-978 Elicited 'Potent Efficacy' Against B-cell ... The single-chain fusion protein CLN-978 elicited “potent efficacy” against B-cell lymphoma cells expressing very low levels of human CD19 (hCD19).

6. acrabstracts.org acrabstracts.org/abstract/cln-978-a-cd19-directed-t-cell-engager-tce-leads-to-rapid-and-deep-b-cell-depletion-and-has-broad-potential-for-development-in-autoimmune-diseases/

CLN-978, a CD19-directed T Cell Engager (TCE), Leads to ... CLN-978 is a highly potent, SC-administered, CD19-directed TCE with both preclinical and clinical data providing a strong rationale for broad development in ...

7. jitc.bmj.com jitc.bmj.com/content/11/8/e007398

CLN-978, a novel half-life extended CD19/CD3/HSA ... The half-life extension and high affinity for CD19 led to significant antitumor activity in murine lymphoma models at very low doses of CLN-978.