CNTY-101 for B-Cell Malignancies

(ELiPSE-1 Trial)

Not currently recruiting at 16 trial locations

Overseen By Nikolaus Trede

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Century Therapeutics, Inc.

Disqualifiers: CNS-only malignancy, CNS pathology, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on testing CNTY-101, a new treatment for certain types of B-cell malignancies, a group of blood cancers. Researchers aim to understand the safety of CNTY-101, how the body processes it, and its effectiveness for people whose cancer has returned or not responded to previous treatments. The trial includes two treatment schedules: one with a single dose and another with three doses over three weeks. Individuals with specific types of non-Hodgkin's lymphoma, such as aggressive NHL, follicular lymphoma, or marginal zone lymphoma, who have undergone multiple treatments, might be suitable for this trial. As a Phase 1 trial, this research seeks 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 mentions a 'washout period' (time without taking certain medications), but it does not specify which medications are prohibited. It's best to discuss your current medications with the trial team to see if any need to be stopped.

Is there any evidence suggesting that CNTY-101 is likely to be safe for humans?

Research has shown that CNTY-101 has generally been well-tolerated in earlier studies. Initial results, shared at a major medical meeting, indicated that the first dose of CNTY-101 was safe for participants. These participants, considered high-risk and previously treated with many other therapies, suggest CNTY-101 might be safe even in challenging cases.

Another study found that multiple doses of CNTY-101 did not cause serious side effects and led to beneficial changes in the cancer environment. As this is still an early phase trial, the treatment is primarily being tested for safety and the correct dosage, with any serious safety concerns closely monitored. Overall, the initial safety data appears promising. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

CNTY-101 is unique because it targets B-cell malignancies using a novel approach. Unlike traditional treatments such as chemotherapy and radiation, CNTY-101 employs engineered natural killer cells to directly attack cancer cells. This method could potentially offer more precise targeting with fewer side effects. Additionally, CNTY-101 can be administered alone or with supplemental interleukin 2, which may enhance the immune response against cancer. Researchers are excited about this treatment because it represents a shift towards harnessing the body's immune system to combat cancer more effectively.

What evidence suggests that CNTY-101 might be an effective treatment for B-cell malignancies?

Research has shown that CNTY-101 holds promise for treating certain blood cancers. Early findings indicate that CNTY-101 was generally safe, even at higher doses, and helped the immune system respond strongly in patients. Specifically, 38% of patients with acute lymphoblastic leukemia (ALL) experienced complete or partial recovery, while 50% of those with diffuse large B-cell lymphoma had positive results. In this trial, participants will receive CNTY-101 in different dosing schedules. One group will receive a single dose, while another group will receive three doses over three weeks. These early results highlight CNTY-101's potential as a new treatment option for people with these types of blood cancers. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

This trial is for people with CD19-positive B-cell Non-Hodgkin's Lymphoma that has come back or hasn't responded to treatment. They must have tried at least two or three prior therapies, including a CD20-targeted agent and an anthracycline or alkylator. Participants should be fairly active (ECOG 0-1), have measurable disease, good organ function, and a life expectancy of over 12 weeks.

Inclusion Criteria

Measurable disease on screening evaluations

My lymphoma is CD19-positive and has come back or didn't respond to treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

Any condition that confounds the ability to interpret data from the study

I have a significant brain or spinal cord condition.

Use of prohibited medications within the washout period defined in the protocol

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CNTY-101 administration

1 week

Treatment

Participants receive CNTY-101, either as a single dose or three doses over three weeks, with or without supplemental IL-2

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• CNTY-101

Trial Overview The ELiPSE-1 study is testing CNTY-101 in patients with certain types of blood cancer. It's the first phase where they're figuring out safe doses, how the body processes the drug, and if it works well against these cancers. Patients will also receive lymphodepleting chemotherapy and IL-2 as part of their treatment.

How Is the Trial Designed?

Group I: Dose Escalation: Schedule B Experimental Treatment 3 Interventions

LDC will be followed by administration of CNTY-101, 3 times over 3 weeks, alone or with supplemental IL-2.

Group II: Dose Escalation: Schedule A Experimental Treatment 3 Interventions

Lymphodepleting chemotherapy (LDC) will be followed by single dose administration of CNTY-101, alone or with supplemental human recombinant interleukin 2 (IL-2).

Who Is Running the Clinical Trial?

Century Therapeutics, Inc.

Lead Sponsor

Trials

3

Recruited

500+

Published Research Related to This Trial

In a phase I study involving 10 patients with refractory diffuse large B-cell lymphoma (DLBCL), the anti-CD19 CAR T cell therapy (C-CAR011) demonstrated a 50% overall response rate at 12 weeks, indicating promising efficacy for this treatment.

The therapy showed a favorable safety profile, with 90% of patients experiencing cytokine release syndrome but no severe (grade ⩾ 3) cases or neurotoxicity, suggesting it is a safe option for patients with heavily treated DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients. Fan, L., Wang, L., Cao, L., et al.[2022]

In a phase 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

Anti-CD19 CAR-modified T cells have demonstrated a 48% overall response rate in treating B-cell malignancies, with complete responses observed in 24% of patients across six phase I clinical trials involving 50 patients.

The study found that conditioning chemotherapy significantly improves progression-free survival (PFS), making it a crucial factor for enhancing the efficacy of CAR T-cell therapy, while the treatment was generally well tolerated with temporary adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. Zhu, Y., Tan, Y., Ou, R., et al.[2022]

In a study of 20 newly diagnosed patients with Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL), Zytux™ showed an overall response rate of 85%, with 35% achieving a complete response and 50% a partial response, indicating its efficacy in treating these conditions.

Zytux™ demonstrated a safety profile comparable to the reference drug MabThera®, suggesting it may be a viable alternative with similar or improved safety and efficacy for patients with NHL and CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of biosimilar rituximab (ZytuxTM) in newly diagnosed patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia. Alwan, AF., Abdulsahib, MA., Abbas, DD., et al.[2020]

Dual-targeting CAR-T cell therapy shows promising efficacy in treating B cell malignancies, with a 77% overall response rate and 52% complete response rate in patients with B cell non-Hodgkin lymphoma (B-NHL), and a 92% complete response rate in patients with B cell acute lymphoblastic leukemia (B-ALL).

The therapy has a manageable safety profile, with grade ≥3 cytokine release syndrome occurring in 14% of B-NHL patients and 11% of B-ALL patients, indicating that while there are risks, the benefits may outweigh them for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dual-Targeting Chimeric Antigen Receptor-T Therapy for Relapsed or Refractory B Cell Lymphoid Malignancies: A Systematic Review and Meta-Analysis. Yu, M., Zhang, Q., Kong, F., et al.[2023]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.7023

A phase 1, multicenter, open-label study of CNTY-101 in ... The first-in-human Phase 1 clinical trial of CNTY-101, ELiPSE-1 (NCT05336409), evaluates safety, preliminary efficacy, PK, and translational biomarkers in ...

2. investors.centurytx.com investors.centurytx.com/news-releases/news-release-details/century-therapeutics-presents-initial-data-cnty-101-phase-1

Century Therapeutics Presents Initial Data from CNTY-101 ... Data presented at 65th ASH Annual Meeting show CNTY-101 was generally well tolerated at Dose Level 1 (100 million cells) in a high-risk, ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1654/502220/Multiple-Doses-of-Cnty-101-an-iPSC-Derived

Multiple Doses of Cnty-101, an iPSC-Derived Allogeneic ... The treatment was associated with changes in tumor microenvironment within 8 days post-infusion, augmentation of adaptive T cell responses, and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497123082575

Multiple Doses of Cnty-101, an iPSC-Derived Allogeneic ... Importantly, tumor microenvironment analyses demonstrated a dramatic increase in T cells within 8 days of the 1 st CNTY-101 cell infusion.

5. withpower.com withpower.com/trial/phase-1-indolent-non-hodgkins-lymphoma-inhl-11-2022-38a40

CNTY-101 for B-Cell Malignancies (ELiPSE-1 Trial) Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05336409?term=AREA%5BBasicSearch%5D(AREA%5BBasicSearch%5D(AREA%5BConditionSearch%5D(%22Lymphoma,%20Hodgkin,%20Classic%22)%20AND%20AREA%5BInterventionSearch%5D(%22interleukin-2%22)))&rank=2

A Study of CNTY-101 in Participants With CD19-Positive B ... ELiPSE-1 is a Phase 1, multi-center, dose-finding study to evaluate the safety, pharmacokinetics, and preliminary efficacy of CNTY-101 in participants with ...