FDA Grants Orphan Drug Designation to LP-284 for High-Grade B-Cell Lymphomas

The FDA has granted orphan drug designation to LP-284 for use in the treatment of patients with high-grade B-cell lymphoma (HGBL) harboring MYC and BCL2 rearrangements, according to an announcement from Lantern Pharma, Inc.¹

LP-284 is a small molecule, next-generation acylfulvene, that damages DNA in cancer cells, leading to their death.

Preclinical data from the 2023 SOHO Annual Meeting showed that when the agent was leveraged as monotherapy or paired with rituximab (Rituxan), it showcased antitumor activity in HGBL.² At day 24 after LP-284 was started at 4 mg/kg, 99% tumor growth inhibition was observed in MYC/BCL2 dual-translocated B-cell non-Hodgkin lymphoma (B-NHL) cell line OCI-LY1-derived xenograft mice. When the agent was given at 2 mg/kg as a monotherapy or with rituximab (n = 4 mice/arm), it led to tumor growth inhibition rates of 57% and 93%, respectively.

“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 of Lantern Pharma, stated in a press release.¹ “…These findings hold significant importance given the elevated rate of relapse and the unfavorable prognosis observed in the majority of [patients with] HGBL.”

The safety and tolerability of the agent will be explored in patients with relapsed or refractory lymphomas and solid tumors as part of a phase 1 trial (NCT06132503) that is not yet recruiting.³ The trial is slated to enroll those who are at least 18 years of age who have an ECOG performance status of 0 to 2 and acceptable organ function.

Those with lymphoma need to have at least 1 bi-dimensionally measurable disease site, with the greatest transverse diameter being 1.5 cm or larger and the greater perpendicular diameter being 1.0 cm or larger at baseline. The lesion also needs to test positive on PET scan. All patients will need to have relapsed and/or refractory disease to 2 or more previous standard therapies or have tumors for which standard options are not available.

If patients have a history or suspicion of central nervous system (CNS) lymphoma or meningeal involvement or CNS metastases, they will be excluded. They also cannot have a history of or active concurrent malignancy other than NHL or solid tumors unless they have been free of disease for at least 2 years. If patients have not yet recovered from clinically significant toxicities from prior treatments or have ongoing unstable cardiovascular function, they will be excluded.

Study participants will receive LP-284 intravenously on days 1, 8, and 15 of a 28-day treatment schedule.

The study will comprise 2 parts. The dose-escalation phase of the research (phase 1a) is estimated to enroll up to 30 evaluable patients and the key objective will be to identify the maximum tolerated dose and/or the recommended phase 2 dose.

The dose-expansion portion of the research (phase 1b) will enroll up to 40 evaluable patients in 2 cohorts: those with mantle cell lymphoma (MCL) and those with diffuse large B-cell lymphoma. Here, investigators will evaluate the safety, tolerability, and clinical activity of the agent, including duration of response, progression-free survival, and overall survival. They will also evaluate the agent’s pharmacokinetic profile.

“This marks the second orphan drug designation granted by the FDA for LP-284. The initial [designation] for LP-284 was granted in January 2023, and with this most recent [designation] for LP-284 announced today, a total of 5 orphan designations have now been granted to Lantern, with the other 3 granted for our drug candidate LP-184,” Sharma added in the news release. “Acquiring these orphan designations is a key element of our business model as they provide a number of benefits including 7 years of market exclusivity and eligibility for expedited drug development programs. Looking forward, these designations further position Lantern to advance our discussions with biopharma companies for partnering and collaborative development opportunities.”

Previously, in January 2023, the FDA granted orphan drug designation to LP-284 for use in patients with MCL.⁴

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, Inc. November 30, 2023. Accessed December 4, 2023. https://ir.lanternpharma.com/news-events/press-releases/detail/143/fda-grants-lantern-pharma-orphan-drug-designation-for-drug
2. Zhou J, Sturtevant D, Biyani N, et al. LP-284 - A highly potent small molecule targeting mantle cell lymphoma. Presented at: 2022 SOHO Annual Meeting; September 28-October 1, 2022; Houston, TX. Poster MCL-319. https://assets-global.website-files.com/606df777a85def5511cf0c80/6500d4fd4af1229f8a7253c2_ABCL-180-Poster.pdf
3. A study of LP-284 in relapsed or refractory lymphomas and solid tumors. ClinicalTrials.gov. Updated November 15, 2023. Accessed December 4, 2023. https://clinicaltrials.gov/study/NCT06132503
4. 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. https://ir.lanternpharma.com/news-events/press-releases/detail/109/fda-grants-lantern-pharma-orphan-drug-designation-for-drug