BAFF-R CAR-T: CR 100%

Recently, PeproMene Bio updated the clinical data of PMB-CT01, a BAFF-R-targeted CAR-T cell therapy, creating a new milestone: 100% Complete Response (CR) with BAFF-R CAR-T.

BAFF-R CAR-T

BAFF-R CAR-T was initially developed at City of Hope.

BAFF-R, a member of the tumor necrosis factor (TNF) receptor superfamily, is the primary receptor for BAFF and is almost exclusively expressed on B cells. It plays a specific role in B cell differentiation and survival. Notably, the broad expression of BAFF-R on malignant B cells makes it a highly valuable tumor target.

Dr. Larry W. Kwak’s lab discovered a novel humanized anti-BAFF-R monoclonal antibody with high binding affinity and cytotoxicity against various B cell tumor cells.

Moreover, since BAFF-R signaling promotes the proliferation and survival of normal B cells, tumor cells are less likely to lose the BAFF-R antigen and escape treatment. This contrasts with CD19 CAR-T therapy, where CD19 antigen loss often leads to relapse. This makes BAFF-R a promising target for CAR-T therapy.

PMB-CT01 is a first-in-class autologous CAR-T cell therapy targeting BAFF-R, invented by Dr. Larry W. Kwak’s lab at City of Hope Comprehensive Cancer Center, where he is Vice President and Associate Director. PeproMene obtained the intellectual property license for PMB-CT01 from City of Hope in 2017.

The CAR in PMB-CT01 incorporates an anti-BAFF-R single-chain variable fragment antibody and a second-generation signaling domain containing CD3ζ and 4-1BB. Studies have shown that BAFF-R CAR-T cells can kill human lymphoma and leukemia cells both in vitro and in vivo.

Currently, PMB-CT01 is in Phase 1 clinical trials, with two ongoing studies targeting relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) (PMB-102; NCT05370430) and relapsed/refractory acute B lymphoblastic leukemia (r/r B-ALL) (PMB-101; NCT04690595).

Early results from PMB-101 and PMB-102 indicate that PMB-CT01 has demonstrated high activity and tolerability in heavily pretreated r/r ALL and r/r NHL patient populations.

CR 100%

Recently, PeproMene updated data from the Phase 1 PMB-102 trial of PMB-CT01 in NHL.

In the PMB-102 study, the first newly enrolled relapsed/refractory follicular lymphoma (FL) patient achieved a complete response (CR) one month after receiving a PMB-CT01 infusion. This patient had previously undergone seven lines of treatment, including chemoimmunotherapy, CD19 CAR-T therapy, investigational trispecific antibodies, and ADC therapy. The patient did not experience cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS).

With this FL patient, a total of seven B-NHL patients in the PMB-102 study have been treated with PMB-CT01, all of whom achieved a complete response (CR 100%) with sustained CR durations (1–29+ months), experiencing only mild grade 1 CRS and ICANS. The data suggest PMB-CT01 offers durable efficacy with manageable safety.

The inclusion of the FL patient also expands the PMB-102 study to include a variety of r/r B-NHL types, such as MCL, DLBCL, and FL.

Additionally, in January 2024, PeproMene reported that the first patient in the PMB-101 trial targeting ALL also achieved a complete response one month after receiving PMB-CT01 treatment.

Summary

Compared with other cancer treatment methods, CAR-T therapy stands out for its high precision and efficacy.

With continuous technological advancements, more and more CAR-T pipelines in recent years have achieved 100% overall response rates (ORR) and even 100% complete response rates (CR), bringing new hope in the fight against cancer.