Science

Yan Leyfman

May 1, 2025, 12:14

Yan Leyfman: A2B694 CAR T Cell Therapy in Solid Tumors

Yan Leyfman, Co-founder and executive director of MedNews Week, shared a post on LinkedIn:

“New Study Spotlight: A2B694 CAR T Cell Therapy in Solid Tumors

CAR T therapies have revolutionized treatment for blood cancers—but applying them to solid tumors has been more complex due to toxicity risks and lack of tumor-specific targets.

Enter A2B694, a logic-gated, mesothelin-targeted CAR T therapy designed to reduce on-target, off-tumor effects. It uses two receptors:
An activator targeting mesothelin (MSLN), expressed on both tumor and normal cells

A blocker that shuts down the activator if it detects HLA-A*02—commonly present in normal cells but often lost in tumor cells.

This selective mechanism offers a potential therapeutic window for treating MSLN+ solid tumors in patients with HLA-A*02 loss of heterozygosity (LOH).

The ongoing EVEREST-2 trial (NCT06051695) is a first-in-human, phase 1/2 study evaluating safety and efficacy of A2B694 in patients with advanced MSLN+ cancers like NSCLC, pancreatic, ovarian, and more. Enrollment is through BASECAMP-1 (NCT04981119), which screens for HLA-A*02 LOH.

First patient enrolled in April 2024. Dose escalation is underway.”

Title: Abstract CT186: EVEREST-2: A seamless phase 1/2 study of A2B694, a logic-gated Tmod CAR T-cell therapy, in patients with mesothelin-expressing solid tumors with human leukocyte antigen-A*02 loss of heterozygosity

Authors: Julian R. Molina; Antonious Hazim; Oliver Dorigo; Salman R. Punekar; Monica Avila; Diane M. Simeone; Kedar Kirtane; Gottfried E. Konecny; Jeffrey Ward; Matthew Block; Jennifer Specht; Leslie Boyd; Yanyan Lou; Jong Chul Park; Jacqueline D. Xuan; Ramez N. Eskander; Gayanie Ong; Marco Davila; Wendy Langeberg; Marcela Maus; Armen Mardiros; Frederick L. Locke; Andrea Wise; David G. Maloney; John Welch; J. Randolph Hecht

You can read the Full Article on Cancer Research.

Yan Leyfman: A2B694 CAR T Cell Therapy in Solid Tumors

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Yan Leyfman: A2B694 CAR T Cell Therapy in Solid Tumors

“New Study Spotlight: A2B694 CAR T Cell Therapy in Solid Tumors

CAR T therapies have revolutionized treatment for blood cancers—but applying them to solid tumors has been more complex due to toxicity risks and lack of tumor-specific targets.

Enter A2B694, a logic-gated, mesothelin-targeted CAR T therapy designed to reduce on-target, off-tumor effects. It uses two receptors:
An activator targeting mesothelin (MSLN), expressed on both tumor and normal cells

A blocker that shuts down the activator if it detects HLA-A02—commonly present in normal cells but often lost in tumor cells.*

This selective mechanism offers a potential therapeutic window for treating MSLN+ solid tumors in patients with HLA-A02 loss of heterozygosity (LOH).*

The ongoing EVEREST-2 trial (NCT06051695) is a first-in-human, phase 1/2 study evaluating safety and efficacy of A2B694 in patients with advanced MSLN+ cancers like NSCLC, pancreatic, ovarian, and more. Enrollment is through BASECAMP-1 (NCT04981119), which screens for HLA-A*02 LOH.

First patient enrolled in April 2024. Dose escalation is underway.”

Science

OncoDaily

Science

Yan Leyfman: A2B694 CAR T Cell Therapy in Solid Tumors

“New Study Spotlight: A2B694 CAR T Cell Therapy in Solid Tumors

CAR T therapies have revolutionized treatment for blood cancers—but applying them to solid tumors has been more complex due to toxicity risks and lack of tumor-specific targets.

Enter A2B694, a logic-gated, mesothelin-targeted CAR T therapy designed to reduce on-target, off-tumor effects. It uses two receptors: An activator targeting mesothelin (MSLN), expressed on both tumor and normal cells

A blocker that shuts down the activator if it detects HLA-A*02—commonly present in normal cells but often lost in tumor cells.

This selective mechanism offers a potential therapeutic window for treating MSLN+ solid tumors in patients with HLA-A*02 loss of heterozygosity (LOH).

The ongoing EVEREST-2 trial (NCT06051695) is a first-in-human, phase 1/2 study evaluating safety and efficacy of A2B694 in patients with advanced MSLN+ cancers like NSCLC, pancreatic, ovarian, and more. Enrollment is through BASECAMP-1 (NCT04981119), which screens for HLA-A*02 LOH.

First patient enrolled in April 2024. Dose escalation is underway.”

Enter A2B694, a logic-gated, mesothelin-targeted CAR T therapy designed to reduce on-target, off-tumor effects. It uses two receptors:
An activator targeting mesothelin (MSLN), expressed on both tumor and normal cells

A blocker that shuts down the activator if it detects HLA-A02—commonly present in normal cells but often lost in tumor cells.*

This selective mechanism offers a potential therapeutic window for treating MSLN+ solid tumors in patients with HLA-A02 loss of heterozygosity (LOH).*