PBCAR0191 for Blood Cancer

Recruiting at 20 trial locations

Overseen By Imugene Clinical Team

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Imugene Limited

Must not be taking: Antivirals, Immunosuppressants

Disqualifiers: CNS disease, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 week

129 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PBCAR0191, targeting blood cancers such as B-ALL (a type of leukemia) and B-cell NHL (a type of lymphoma). The goal is to evaluate the safety and effectiveness of azer-cel, a type of CAR T-cell therapy that modifies immune cells to fight cancer. Participants will receive varying doses to determine the optimal and safest amount. This trial may suit individuals with specific aggressive blood cancers who have already tried two or more treatments without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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, it mentions that participants should not have received certain cancer treatments or live vaccines within specific time frames before starting the trial. It's best to discuss your current medications with the trial team to get a clear answer.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that azer-cel, also known as PBCAR0191, has been tested for safety in people with certain blood cancers. Early results suggest it is generally well-tolerated. Some patients have experienced side effects, but these are often manageable. For instance, studies found that adjusting the dose can help manage risks, highlighting the importance of careful dosing.

While more information is needed to fully understand its safety, these early studies provide valuable insights. As this treatment remains in the early testing stages, scientists are primarily focused on finding the right dose and checking for any serious side effects. Interested individuals should consult a doctor to understand how these findings might apply to them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about PBCAR0191 for blood cancer because it utilizes a cutting-edge approach called CAR T-cell therapy. Unlike standard treatments like chemotherapy or radiation, CAR T-cell therapy involves genetically modifying a patient's own T-cells to better recognize and attack cancer cells. This personalized method not only offers a targeted attack on cancer but has also shown promise in cases where traditional therapies have failed. Furthermore, the different dosing levels being tested could lead to a more effective and customizable treatment plan, maximizing patient outcomes while minimizing side effects.

What evidence suggests that PBCAR0191 might be an effective treatment for blood cancer?

Research has shown that PBCAR0191, also known as azer-cel, holds promise for treating certain blood cancers. This trial evaluates various dose levels of azer-cel, each as a separate treatment arm, to determine the most effective and safe dosage. Studies have found that azer-cel can lead to high response rates in patients with relapsed or hard-to-treat diffuse large B-cell lymphoma (DLBCL), a type of non-Hodgkin lymphoma. In some cases, azer-cel has even resulted in complete responses, meaning the cancer becomes undetectable after treatment. This treatment uses CAR T-cells, specially modified immune cells that seek out and destroy cancer cells. Early findings suggest that the right dose of azer-cel can be given safely and may have strong cancer-fighting effects. ^{1 2 3 4 5}

Who Is on the Research Team?

John Byon, MD, PhD

Principal Investigator

Imugene Limited

Are You a Good Fit for This Trial?

Adults with aggressive CD19+ B-cell Non-Hodgkin's Lymphoma (NHL) or relapsed/refractory B-cell Acute Lymphoblastic Leukemia (ALL), who have tried at least two prior treatments, can join this trial. They should not have severe heart, lung, kidney, liver issues or active infections and must be HIV negative. Those with a history of CNS disease need to show clear recovery.

Inclusion Criteria

I have had only one treatment for the aggressive part of my lymphoma.

My heart, lungs, liver, kidneys, and bone marrow are functioning well.

My kidney function, measured by eGFR, is above 30 mL/min.

Exclusion Criteria

I have another cancer type that might return in the next 2 years, besides my current B-ALL or NHL.

I have active hepatitis B or C, or I have inactive hepatitis B and am on preventive treatment.

I need urgent treatment because my tumor is causing blockages or pressing on blood vessels.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants receive lymphodepletion treatment prior to azer-cel administration

1 week

Treatment

Participants receive intravenous infusion of azer-cel on Day 0 and Day 5

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

720 days

Long-term follow-up

Participants are followed in a separate long-term follow-up study for up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• PBCAR0191

Trial Overview

The study is testing PBCAR0191 in combination with Fludarabine and Cyclophosphamide for safety and effectiveness in treating NHL and ALL. It involves gradually increasing the dose to find the best balance between benefits and side effects.

How Is the Trial Designed?

Group I: Dose level 4c Experimental Treatment 3 Interventions

Azer-cel, 1000 x 10\^6 CAR T cells (flat dose) given as 2 administrations of 500 × 106 cells/per dose on Day 0 and Day 5.

Group II: Dose Level 4b Experimental Treatment 5 Interventions

Azer-cel, 500 x 10\^6 CAR T cells (flat dose)

Group III: Dose Level 4 Experimental Treatment 3 Interventions

Azer-cel, 6 x 10\^6 CAR T cells per kg body weight as 2 administrations of 3 x 10\^6 CAR T cells per kg body weight administered after a single lymphodepletion.

Group IV: Dose Level 3a Experimental Treatment 3 Interventions

Azer-cel, 3 x 10\^6 CAR T cells per kg body weight.

Group V: Dose Level 2 Experimental Treatment 3 Interventions

Azer-cel, 1 x 10\^6 CAR T cells per kg body weight

Group VI: Dose Level 1 Experimental Treatment 3 Interventions

Azer-cel 3 x 10\^5 CAR T cells per kilogram (kg) body weight. Route of Administration: Intravenous infusion.

Who Is Running the Clinical Trial?

Imugene Limited

Lead Sponsor

Trials

7

Recruited

340+

Precision BioSciences, Inc.

Lead Sponsor

Trials

6

Recruited

330+

Published Research Related to This Trial

In a phase 1 study involving 57 patients with relapsed/refractory multiple myeloma, LCAR-B38M CAR T cell therapy showed an impressive overall response rate of 88%, with 68% of patients achieving a complete response.

While the therapy had a manageable safety profile, with common adverse events including leukopenia and cytokine release syndrome, it demonstrated durable responses with a median progression-free survival of 15 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1, open-label study of LCAR-B38M, a chimeric antigen receptor T cell therapy directed against B cell maturation antigen, in patients with relapsed or refractory multiple myeloma. Zhao, WH., Liu, J., Wang, BY., et al.[2020]

CAR T-cell therapies, such as tisagenlecleucel (Kymriah™) and axicabtagene ciloleucel (Yescarta™), are effective treatments for relapsed/refractory B-cell acute lymphoblastic leukemia and diffuse large B-cell lymphoma, utilizing genetically modified T cells that target the CD19 antigen.

These therapies are classified as 'living drugs' because they involve the genetic engineering of a patient's own T cells, highlighting the importance of proper collection and manufacturing processes for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. Carnoy, S., Beaumont, JL., Kanouni, T., et al.[2021]

Chimeric antigen receptor (CAR) T-cell therapy targeting the CD19 antigen has shown high effectiveness in treating patients with relapsed or refractory B-cell malignancies, with several therapies like tisagenlecleucel already approved in Japan.

Research is ongoing for CAR T-cell therapies targeting other cancers, such as acute myeloid leukemia (AML) and multiple myeloma, indicating a broadening scope of CAR T-cell applications beyond just B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chimeric antigen receptor T-cell therapy for hematological malignancies]. Nakazawa, Y.[2019]

In a study of 182 patients with relapsed/refractory large B-cell lymphoma, novel CAR T-cell therapies showed varying efficacy and safety compared to the FDA-approved Yescarta, with some constructs like tandem CD19.CD20.4-1BBζ demonstrating favorable outcomes.

While some experimental CARs had improved safety profiles, they did not consistently outperform Yescarta in terms of progression-free survival, indicating that further research is needed to establish the best treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Innovative Experimental Chimeric Antigen Receptor (CAR) T-cells versus Axicabtagene ciloleucel (Yescarta) for the Treatment of Relapsed/Refractory Large B-Cell Lymphoma (LBCL): Matching Adjusted Indirect Comparisons (MAICs) and Systematic Review. Weinstein, B., Muresan, B., Solano, S., et al.[2022]

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. Meng, J., Wu, X., Sun, Z., et al.[2022]

In a phase 1 trial of 53 adults with relapsed B-cell acute lymphoblastic leukemia, 83% achieved complete remission after receiving CD19-specific CAR T cells, indicating high initial efficacy.

Patients with a low disease burden before treatment experienced significantly longer overall survival (20.1 months) and fewer severe side effects, such as cytokine release syndrome, compared to those with a higher disease burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. Park, JH., Rivière, I., Gonen, M., et al.[2023]

Cytokine release syndrome (CRS) is the most common adverse reaction reported after CAR-T therapy, with significantly higher reports for axicabtagene ciloleucel compared to tisagenlecleucel, indicating a need for careful monitoring of this side effect.

The study analyzed 1426 reports of adverse drug reactions from real clinical settings, supporting the overall safety profile of CAR-T therapies while confirming CRS as a major concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. Bonaldo, G., Montanaro, N., AlbertoVaccheri, ., et al.[2021]

CAR T cell therapy, particularly targeting B cell maturation antigen (BCMA), has shown promising efficacy in early clinical trials for treating multiple myeloma, indicating its potential as a new treatment option.

Recent research has also demonstrated that CAR T cells targeting activated integrin β7 can effectively eliminate multiple myeloma cells, including specific B cell types, and preparations for a clinical trial are underway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy for multiple myeloma. Hasegawa, K., Hosen, N.[2020]

In a retrospective analysis of 7 patients with prior allogeneic stem cell transplants (alloSCT) who received cilta-cel, an overall response rate of 85.7% was observed, indicating that cilta-cel is effective even in this heavily pretreated group.

The safety profile of cilta-cel in patients with prior alloSCT was similar to that of patients without alloSCT, with manageable side effects like cytokine release syndrome and no reported cases of graft-versus-host disease, suggesting that cilta-cel may be a viable treatment option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene Autoleucel in Patients With Prior Allogeneic Stem Cell Transplant in the CARTITUDE-1 Study. Htut, M., Dhakal, B., Cohen, AD., et al.[2023]

Chimeric antigen receptor T-cells (CAR-T) targeting the CD19 antigen have shown remarkable success in treating relapsed/refractory B-cell malignancies, leading to their approval in various regions, including the European Union.

The academic CAR-T product varnimcabtagene autoleucel (var-cel) has been specifically approved in Spain for patients over 25 with relapsed/refractory acute lymphoblastic leukemia, highlighting its significance and the regulatory support it has received, including Priority Medicines designation from the European Medicines Agency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Practical aspects of chimeric antigen receptor T-cell administration: From commercial to point-of-care manufacturing. Martinez-Cibrian, N., Español-Rego, M., Pascal, M., et al.[2022]

Axicabtagene ciloleucel is a promising CAR T cell therapy specifically designed to target CD19-positive cancers, showing strong antitumor activity in patients with refractory diffuse large B cell lymphoma (DLBCL).

The therapy is made from the patient's own T cells, which are engineered to recognize cancer cells, but it can cause significant side effects like cytokine release syndrome and neurological events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel, a first-in-class CAR T cell therapy for aggressive NHL. Roberts, ZJ., Better, M., Bot, A., et al.[2019]

Citations

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clinicaltrials.gov

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Study Details | NCT03666000 | Dose-escalation, ...

This is a multicenter, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and tolerability, find ...

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ashpublications.org

ashpublications.org/blood/article/140/Supplement%201/4588/490591/Effective-Cell-Dose-and-Functional-Attributes-of

PBCAR0191) Associate with Allogeneic CAR T-Cell Safety ...

Effective cell dose and functional attributes of azercabtagene zapreleucel (azer-cel; PBCAR0191) associate with allogeneic CAR T-cell safety and efficacy.

3.

targetedonc.com

targetedonc.com/view/optimizing-r-r-dlbcl-treatment-azer-cel-shows-sustained-responses

Optimizing R/R DLBCL Treatment: Azer-Cel Shows ...

Promising results emerge from a phase 1b trial of azer-cel, an innovative CAR T-cell therapy, showing high response rates in DLBCL patients.

4.

investor.precisionbiosciences.com

investor.precisionbiosciences.com/news-releases/news-release-details/precision-biosciences-presents-analysis-azer-cel-allogeneic-car

Precision BioSciences Presents Analysis of Azer-Cel, ...

Cryopreserved, Post-thaw CAR T Cell Composition and Effective CAR T Cell Dose are Predictive for Response to Treatment with Azer-cel.

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onclive.com

onclive.com/view/azer-cel-produces-crs-in-r-r-dlbcl-after-prior-autologous-car-t-cell-therapy

Azer-Cel Produces CRs in R/R DLBCL After Prior ...

Azercabtagene zapreleucel produced complete responses in relapsed/refractory diffuse large B-cell lymphoma after prior autologous CAR T-cell therapy.