FDA Grants Orphan Drug Designation to LP-284 in High-Grade B-Cell Lymphoma

Investigators have launched a first-in-human phase 1 trial (NCT06132503) that will evaluate LP-284 as a treatment for those with B-cell non-Hodgkin lymphoma, including patients with high-grade B-cell lymphoma and mantle cell lymphoma (MCL).

The novel small molecule agent LP-284 has earned orphan drug designation from the FDA as a therapy for patients with high-grade B-cell lymphoma harboring MYC and BCL2 rearrangements, according to a press release from Lantern Pharma Inc.¹

“Receiving orphan drug designation is an important milestone for our latest drug candidate, LP-284, and further validates our data-driven approach to oncology drug discovery and development,” Panna Sharma, president and chief executive officer at Lantern Pharma, said in the press release.¹

Investigators previously presented data highlighting the potential clinical activity of LP-284 when administered alone or in combination with rituximab (Rituxan) at the 2023 Society of Hematologic Oncology (SOHO) Annual Meeting. Findings from the research supported the conclusion that LP-284 was capable of yielding lethal DNA double-strand breaks in addition to demonstrating robust anti-tumor activity in xenograft mouse models with homologous recombination deficiency–positive B-cell non-Hodgkin lymphoma.²

“These findings hold significant importance given the elevated rate of relapse and the unfavorable prognosis observed in the majority of patients [with high-grade B-cell lymphoma],” Sharma said.¹

Investigators have launched a first-in-human phase 1 trial (NCT06132503) that will evaluate LP-284 as a treatment for those with B-cell non-Hodgkin lymphoma, including patients with high-grade B-cell lymphoma and mantle cell lymphoma (MCL). The phase 1a dose escalation portion of the study will determine the maximum tolerated dose of LP-284, and the phase 1b dose expansion portion will assess the preliminary clinical activity of the agent.

The trial’s primary end points include safety and tolerability, maximum tolerated dose, and recommended phase 2 dose in phase 1a as well as preliminary estimates of clinical activity in phase 1b. Secondary end points include pharmacokinetics, objective response rate, duration of response, progression-free survival, and overall survival.

Patients 18 years and older with histologically confirmed B-cell non-Hodgkin lymphoma based on 2016 World Health Organization criteria and an ECOG performance status of 0 to 2 at screening are able to enroll on the study. Additional eligibility criteria include having at least 1 bio-dimensionally measurable disease site if diagnosed with lymphoma, adequate organ function, and resolved acute toxicity from any prior therapy.

Those with suspected central nervous system (CNS) lymphoma or meningeal involvement or CNS metastases or another concurrent malignancy besides non-Hodgkin lymphoma or solid tumors are not able to enroll on the study. Patients are also unsuitable for enrollment if they have ongoing unstable cardiovascular function; infection requiring treatment with antibiotics, antifungals, or underwent treatment with antivirals within 1 week of initiating study treatment; prior allogeneic hematopoietic stem cell transplantation; or radiotherapy within 4 weeks of beginning study treatment. Having hepatitis B and/or hepatitis C serology or receiving a live vaccine within 1 month of beginning treatment with LP-284 is also grounds for exclusion from the trial.

The FDA previously granted orphan drug designation to LP-284 as a therapy for those with MCL in January 2023.³

References

1. FDA grants Lantern Pharma orphan drug designation for drug candidate LP-284 in high-grade B-cell lymphomas (HGBL). News release. Lantern Pharma. November 30, 2023. Accessed December 4, 2023. https://bit.ly/3Nb5juZ
2. Zhou J, Sturtevant D, Ewesuedo R, Bhatia K. Targeting homologous recombination deficiencies in B-Cell non-Hodgkin’s lymphomas with the novel anti-tumor small molecule LP-284. Presented at: 2023 Society of Hematologic Oncology (SOHO). Annual Meeting; September 6-9, 2023; Houston, TX; Abstract ABCL-180.
3. FDA grants Lantern Pharma orphan drug designation for drug candidate LP-284 in mantle cell lymphoma. News release. Lantern Pharma. January 5, 2023. Accessed December 4, 2023. yhoo.it/3H82EiR