Trial to assess dual CAR T-cell therapy for children, young adults with leukemia

Rebecca A. Gardner

A trial is underway to evaluate the use of dual chimeric antigen receptor T-cell immunotherapy for children and young adults with relapsed or refractory CD19- and CD22-positive acute lymphoblastic leukemia.

“This is an exciting time where we are at the forefront of advancing the CAR T-cell immunotherapy field by pioneering strategies to improve long-term outcomes for children and young adults,” Rebecca A. Gardner, MD, attending physician in the department of pediatric hematology-oncology at Seattle Children’s Hospital, said in a press release. “In launching a bilateral attack on the cancer cells, we hope this trial will help us develop a T-cell therapy that leads to long-term remission for many more of our patients.”

The PLAT-05 trial builds upon data from the PLAT-02 trial, which showed patients relapse for one of two reasons — they either lose persistence of their reprogrammed CAR T cells, or the leukemia evolves to circumvent the CAR T cells.

Gardner and colleagues aim to reprogram CAR T cells to detect and destroy leukemia cells by targeting both the CD19 and CD22 proteins upfront. If the cancer evolves to no longer express CD19, the CAR T cells can still attack the cancer through the identification of the CD22 protein.

“[Although] we are pleased that we have been able to get patients who are very sick into remission —some have been in remission for more than 3 years — we want all of our patients to be cancer free for life,” Gardner said. “That is what we are working toward.”

HemOnc Today spoke with Gardner about the study, the rationale for this dual-targeting approach and the benefits it may confer.

 

Question: How will the study be conducted?

Answer: We are accruing patients who will come to Seattle Children’s Hospital to enroll in the dose-finding study. We have two dose levels, with the possibility of three dose levels, to truly understand if this CAR T-cell therapy is similar to other CAR T-cell products or if it is different and then make adjustments as needed.

 

Q: How many patients will be enrolled, and who is eligible?

A: We anticipate having 25 to 35 patients enrolled on this study. We are looking for patients with acute leukemia that expresses both CD19 and CD22. Patients with only one of these will not be enrolled on PLAT-05, but they will have the potential to be enrolled on a single-target study. The age range of patients is between 1 year and 26 years. Patients are required to have adequate organ function so that, if there are side effects, they will be capable of handling those side effects.

 

Q: What is the rationale for this dual-targeting approach?

A: We have learned from prior trials that a substantial portion of patients relapsed with CD19-negative leukemia —the leukemia outsmarted the CAR T cells. The idea with this dual-targeting antigen is that we can cut down the risk for this and keep patients in a longer-term remission. NCI has published data on CD22 CAR T cells, but these T cells do not look to be curative alone in the way that we potentially think that CD19 cells are curative, so either CD19 or CD22 alone has some risk for patients to become antigen negative.

 

Q: How does this approach differ from the traditional approach with CAR T-cell therapy?

A: The biggest difference is that it is targeting two proteins expressed by the leukemia cells at the same time rather than only targeting one protein. We think that, if we put both CD22 and CD19 on at the same time, we can help keep patients in a longer remission.

 

Q: What is the timeline for accrual and data availability?

A: We think it will probably take 12 to 18 months for us to meet our accrual goals. Hopefully at that time we will have initial data available. However, it will take longer than this to look at the durability of remission. The first thing we will look at is the safety of this product and whether it is the same in terms of other CAR T-cell products. The second part that we will look at is whether it works as well as single CAR T-cell therapy in terms of remission. We hope to have this data within the 12- to 18-month timeline. What will take a little longer to find out is whether the patients who go into remission actually stay in remission long term or if they relapse, and if they do relapse, are they relapsing with CD19-negative leukemia or CD22-negative leukemia?

 

Q: Does this dual-targeting approach raise any additional potential safety concerns , or do you expect the safety of this approach to be similar to therapies that target CD19 or CD22 alone?

A: We do not yet know the answer to this, but we hope it will be similar. However, we will look to see if it is more toxic.

 

Q: Is there anything else that you would like to mention?

A: I am excited that we are doing this work and getting the word out. This is an exciting time in oncology and we are ecstatic to see the field of immunotherapy advancing. Ultimately, we see this therapy moving to patients when they are initially diagnosed. – by Jennifer Southall

 

For more information:

Rebecca A. Gardner, MD, can be reached at Seattle Children’s Hospital, MB.8.501 — Hematology-Oncology, 4800 Sand Point Way NE, Seattle, WA 98105.

 

Disclosure: Gardner reports no relevant financial disclosures.

Rebecca A. Gardner

A trial is underway to evaluate the use of dual chimeric antigen receptor T-cell immunotherapy for children and young adults with relapsed or refractory CD19- and CD22-positive acute lymphoblastic leukemia.

“This is an exciting time where we are at the forefront of advancing the CAR T-cell immunotherapy field by pioneering strategies to improve long-term outcomes for children and young adults,” Rebecca A. Gardner, MD, attending physician in the department of pediatric hematology-oncology at Seattle Children’s Hospital, said in a press release. “In launching a bilateral attack on the cancer cells, we hope this trial will help us develop a T-cell therapy that leads to long-term remission for many more of our patients.”

The PLAT-05 trial builds upon data from the PLAT-02 trial, which showed patients relapse for one of two reasons — they either lose persistence of their reprogrammed CAR T cells, or the leukemia evolves to circumvent the CAR T cells.

Gardner and colleagues aim to reprogram CAR T cells to detect and destroy leukemia cells by targeting both the CD19 and CD22 proteins upfront. If the cancer evolves to no longer express CD19, the CAR T cells can still attack the cancer through the identification of the CD22 protein.

“[Although] we are pleased that we have been able to get patients who are very sick into remission —some have been in remission for more than 3 years — we want all of our patients to be cancer free for life,” Gardner said. “That is what we are working toward.”

HemOnc Today spoke with Gardner about the study, the rationale for this dual-targeting approach and the benefits it may confer.

 

Question: How will the study be conducted?

Answer: We are accruing patients who will come to Seattle Children’s Hospital to enroll in the dose-finding study. We have two dose levels, with the possibility of three dose levels, to truly understand if this CAR T-cell therapy is similar to other CAR T-cell products or if it is different and then make adjustments as needed.

 

Q: How many patients will be enrolled, and who is eligible?

A: We anticipate having 25 to 35 patients enrolled on this study. We are looking for patients with acute leukemia that expresses both CD19 and CD22. Patients with only one of these will not be enrolled on PLAT-05, but they will have the potential to be enrolled on a single-target study. The age range of patients is between 1 year and 26 years. Patients are required to have adequate organ function so that, if there are side effects, they will be capable of handling those side effects.

 

Q: What is the rationale for this dual-targeting approach?

A: We have learned from prior trials that a substantial portion of patients relapsed with CD19-negative leukemia —the leukemia outsmarted the CAR T cells. The idea with this dual-targeting antigen is that we can cut down the risk for this and keep patients in a longer-term remission. NCI has published data on CD22 CAR T cells, but these T cells do not look to be curative alone in the way that we potentially think that CD19 cells are curative, so either CD19 or CD22 alone has some risk for patients to become antigen negative.

 

Q: How does this approach differ from the traditional approach with CAR T-cell therapy?

A: The biggest difference is that it is targeting two proteins expressed by the leukemia cells at the same time rather than only targeting one protein. We think that, if we put both CD22 and CD19 on at the same time, we can help keep patients in a longer remission.

 

Q: What is the timeline for accrual and data availability?

A: We think it will probably take 12 to 18 months for us to meet our accrual goals. Hopefully at that time we will have initial data available. However, it will take longer than this to look at the durability of remission. The first thing we will look at is the safety of this product and whether it is the same in terms of other CAR T-cell products. The second part that we will look at is whether it works as well as single CAR T-cell therapy in terms of remission. We hope to have this data within the 12- to 18-month timeline. What will take a little longer to find out is whether the patients who go into remission actually stay in remission long term or if they relapse, and if they do relapse, are they relapsing with CD19-negative leukemia or CD22-negative leukemia?

 

Q: Does this dual-targeting approach raise any additional potential safety concerns , or do you expect the safety of this approach to be similar to therapies that target CD19 or CD22 alone?

A: We do not yet know the answer to this, but we hope it will be similar. However, we will look to see if it is more toxic.

 

Q: Is there anything else that you would like to mention?

A: I am excited that we are doing this work and getting the word out. This is an exciting time in oncology and we are ecstatic to see the field of immunotherapy advancing. Ultimately, we see this therapy moving to patients when they are initially diagnosed. – by Jennifer Southall

 

For more information:

Rebecca A. Gardner, MD, can be reached at Seattle Children’s Hospital, MB.8.501 — Hematology-Oncology, 4800 Sand Point Way NE, Seattle, WA 98105.

 

Disclosure: Gardner reports no relevant financial disclosures.

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