FDA Clears LP-184 IND for TNBC Trial as Monotherapy & PARP Inhibitor Combo
A phase 1b/2 trial in triple-negative breast cancer will assess LP-184 alone and with a PARP inhibitor in advanced cases.
US FDA
- The investigational new drug (IND) application for LP-184 has been cleared by the FDA.
- With this clearance, a phase 1b/2 trial of the agent will begin in triple-negative breast cancer (TNBC).
- The trial will assess LP-184 as monotherapy and in combination with a PARP inhibitor.
The FDA has cleared the IND application of LP-184, paving the way for a phase 1b/2 trial to investigate the agent in TNBC.1
"This IND clearance for LP-184 in a phase 1b/2 study represents a pivotal advancement in our mission to bring precisely targeted, AI-developed medicines to patients with aggressive cancers and limited treatment options," said Panna Sharma, chief executive officer and president of Lantern Pharma, in a press release. "The strategic design of our clinical program reflects both the compelling mechanistic rationale and the encouraging data supporting LP-184's potential in TNBC."
With an average survival of 10 to 18 months for patients with newly diagnosed metastatic TNBC, LP-184 could address a significant unmet medical need.
The study will evaluate LP-184 in patients with recurrent, advanced-stage TNBC as a monotherapy and in combination with a PARP inhibitor. In the monotherapy arm, the goal is to focus on dose optimization to enhance safety and efficacy. Two dose levels of LP-84 will be assessed, and about 30 patients will be enrolled in this group.
The combination arm will enroll patients with advanced-stage TNBC harboring BRCA1 or BRCA2 alterations, and patients will be dosed with LP-184 and olaparib (Lynparza). In preclinical studies, LP-184 has shown high potency when combined with a PARP inhibitor, including in tumors that are PARP inhibitor resistant.
About LP-184
Medical illustration of breast cancer
LP-184 is a small molecule that induces DNA double-strand breaks when activated by prostaglandin reductase 1 in cancer cells. Preclinical models show that cancers with DNA damage repair (DDR) alterations may have improved responses to LP-184. An estimated 70% of cases of TNBC harbor homologous recombination pathway deficiencies, which could make them particularly sensitive to LP-184.
Further, LP-184 has shown blood-brain barrier penetration preclinically, which is another important feature, as up to 46% of patients with TNBC will develop brain metastases.
LP-184 has previously been awarded fast track, orphan drug, and rare pediatric disease designations. In December 2024, the FDA awarded fast track designation to LP-184 in TNBC.2
LP-184 has shown promise as a potential therapy for solid tumors with DDR mutations, including lung, bladder, pancreatic, and ovarian cancers.1 Through a preclinical collaboration with MD Anderson, LP-184 combined with checkpoint inhibitors showed that it was able to turn immunologically “cold” tumors “hot” by reshaping the tumor microenvironment and modulating T-cell activity.3
