FDA Grants Orphan Drug Designation to LP-284 for Soft Tissue Sarcoma

The FDA has granted orphan drug designation (ODD) to LP-284, a next-generation acylfulvene small molecule, for the treatment of soft tissue sarcomas (STS). This is the third orphan designation for LP-284 following designations for mantle cell lymphoma (MCL) and high-grade B-cell lymphoma (HGBL).¹

The Clinical Burden of Soft Tissue Sarcomas

Soft tissue sarcomas represent a rare heterogeneous group of mesenchymal malignancies, accounting for approximately 1% of adult and 21% of pediatric cancers in the United States. An estimated 13,520 new cases of STS were diagnosed in the US in 2025, with approximately 5420 deaths attributed to the disease.² Globally, the annual incidence of STS is estimated at 96,000 cases.³

The management of advanced or metastatic STS remains a profound clinical challenge. Although localized tumors often respond well to surgical resection, the prognosis for metastatic disease is poor, with a 5-year survival rate of 16.7%. Standard-of-care systemic therapies often yield short-lived responses, and many patients quickly exhaust available lines of treatment. This underscores the urgent need for novel agents that can circumvent traditional resistance mechanisms.

Mechanism of Action: Targeting DNA Damage Response

LP-284 is a computationally optimized small molecule designed to exploit specific vulnerabilities in cancer cells with DNA damage response (DDR) deficiencies.⁵ Its primary mechanism involves a synthetic lethal approach targeting cells with impaired transcription-coupled nucleotide excision repair (NER). By inducing lethal double-strand DNA breaks (DSBs), LP-284 preferentially targets malignant cells that lack the robust repair machinery necessary to maintain genomic stability.

Preclinical and early clinical studies supported its use in hematologic malignancies with observed activity independent of TP53 mutation status or surface antigen expression. Adult sarcomas typically exhibit complex genomic alterations, chromosomal instability, and DDR deficiencies, as opposed to pediatric sarcomas driven by gene fusions. These molecular characteristics align with the profile of LP-284. Recent studies indicate that approximately 9.6% of bone and soft tissue sarcomas harbor oncogenic somatic DDR alterations, with some subtypes showing significantly higher rates.⁶

Clinical Validation and Future Directions

LP-284 is being investigated in an ongoing first-in-human phase 1 trial (NCT06132503) in patients with B-cell non-Hodgkin lymphoma including MCL and HGBL as well as other solid tumors. As of October 2025, the trial has enrolled 13 patients across 5 dose levels and completed the monitoring period for 4 of 5 escalating dose levels without any dose-limiting toxicity.

In 2025, Lantern Pharma reported that a heavily pretreated 41-year-old patient with aggressive grade 3 diffuse large B-cell lymphoma who had disease progression after frontline chemoimmunotherapy, chimeric antigen receptor T-cell therapy, and bispecific antibody therapies achieved a complete metabolic response with non-avid lesions after only 2 cycles of LP-284.^1,7

The granting of ODD provides Lantern Pharma with several key incentives to accelerate development, including 7 years of marketing exclusivity following FDA approval, tax credits for qualified clinical trial expenses, and waiver of PDUFA application fees.

“Receiving orphan drug designation for LP-284 in soft tissue sarcomas expands this molecule’s potential beyond hematologic malignancies into solid tumors,” said Panna Sharma, CEO of Lantern Pharma, in a news release.¹

REFERENCES

1. Lantern Pharma’s LP-284 Receives FDA Orphan Drug Designation for Soft Tissue Sarcomas. News release. Lantern Pharma. January 20, 2026. Accessed January 20, 2026. https://tinyurl.com/mr3x34mr

2. Soft Tissue Sarcoma Treatment (PDQ®)–Health Professional Version. National Cancer Institute. Updated February 21, 2025. Accessed January 20, 2026. https://tinyurl.com/4htua6zn

3. Zhou J, Xu S, Long Y, et al. Global burden of soft tissue sarcomas in 204 countries and territories from 1990 to 2021: data from the global burden of disease study 2021. BMC Public Health. 2025;25(1):1519. doi:10.1186/s12889-025-22782-5

4. 2025 Sarcoma Statistics. Sarcoma Foundation of America. Accessed January 20, 2026. https://tinyurl.com/2vr9s5sx

5. Zhou J, Sturtevant D, Love C, et al. LP-284, a small molecule acylfulvene, exerts potent antitumor activity in preclinical non-Hodgkin's lymphoma models and in cells deficient in DNA damage repair. Oncotarget. 2023;14:597-611. doi:10.18632/oncotarget.28454

6. Nacev BA, Sanchez-Vega F, Smith SA, et al. Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets. Nat Commun. 2022;13(1):3405. Published 2022 Jun 15. doi:10.1038/s41467-022-30453-x

7. Patel K, McKean W, Abdulla N, Zhou J, Ewesuedo R, Philipovskiy A. A Phase 1 Study of LP-284 in Adult Patient with Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas and Solid Tumors. Presented at: Lymphoma, Leukemia, and Myeloma Congress 2025; October 14-17, 2025; New York, NY. Abstract PO52. https://tinyurl.com/rpcjbdct