A Phase 1 Study of LP-284 in Adult Patient with Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas and Solid Tumors

Introduction/Background/Significance: Background: Treating aggressive relapsed or refractory (R/R) non-hodgkin lymphoma (NHL) can be challenging, especially for those patients progressing after CAR T-cell therapy or those with high-risk features such as MYC/BCL2 rearrangements and ATM mutations. LP-284 is a fully synthetic small molecule that kills cancer cells via DNA damage. LP-284 has also been shown to downregulate gene expression pathways associated with lymphoma pathogenesis. Preclinical studies have shown LP-284's cytotoxicity against various human mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines and cell line-derived xenograft models, even those resistant to targeted therapies and/or with high-risk features. Given its compelling anti-tumor activities, LP-284 has been granted FDA orphan drug designations for the treatment of MCL and the treatment of high-grade lymphoma with MYC/BCL dual rearrangements, respectively.

Materials and Methods/Case Presentation/Objective: Design and Methods: This ongoing single arm study (NCT06132503) has two parts: Phase 1a for dose escalation and Phase 1b for dose expansion. LP-284 is administered intravenously on Days 1, 8, and 15 of each 28-day cycle. The Phase 1a part enrolls adult patients with R/R NHL and solid tumors. The primary objectives are to evaluate the safety and tolerability of escalating doses of LP-284 and to determine the recommended Phase 2 dose (RP2D) and/or the maximum tolerated dose (MTD). The secondary objectives are to characterize the pharmacokinetics of LP-284 and assess its preliminary clinical activity. Upon completion of Phase 1a, the Phase 1b part will enroll adult patients with R/R MCL and DLBCL, who will receive one of the two dose levels evaluated in Phase 1a, with the primary objective of evaluating LP-284's clinical activities. Status: Thirteen patients have been enrolled across five dose levels in the Phase 1a part. Notably, a DLBCL patient who was failed by 3 prior therapies, including a CAR T-cell therapy, achieved a complete metabolic response after 2 cycles of LP-284 treatment. Dose levels 1-4 have completed the dose-limiting toxicity (DLT) monitoring period without any DLT. Enrollment at dose level 5 is ongoing.