Phase 1 data showed that LP-184 displayed an acceptable safety profile and was well-tolerated in heavily-pretreated patients with advanced solid tumors.
Treatment with the biomarker-activated drug candidate LP-184 demonstrated safety, tolerability, and early signs of efficacy in heavily pretreated patients with advanced solid tumors, many of which were DNA damage repair (DDR) deficient, meeting all primary end points in dose-escalation portion of a phase 1/2 study (NCT05933265).1,2
Notably, patients on the study (n = 63) had received a median of 3 or more prior lines of therapy.1 A clinical benefit rate of 8% was observed with LP-184 at 6 or more months in DDR-altered tumors, and the disease control rate was 54%.
Regarding safety, the most common adverse effects (AEs) included nausea, vomiting, thrombocytopenia, and reversible transaminitis, all of which were clinically manageable and consistent with known toxicities for this drug class.
The recommended phase 2 dose (RP2D) of the agent was also established in phase 1a.
"These are patients who had exhausted standard options, yet several remain on LP-184 with meaningful clinical benefit in challenging cancers one to two years later. This durability in genomically selected, end-stage cancer patients is encouraging and directly validates the predictive power of our RADR AI platform and the PTGR1 biomarker,” Panna Sharma, president and chief executive officer of Lantern Pharma, stated in a news release. “With a diagnostic-ready molecular assay for PTGR1, strong enthusiasm from key opinion leaders and multiple FDA designations in hand, Lantern plans on advancing LP-184 into multiple precision phase 1b/2 trials targeting indications with aggregate annual [United States] market potential exceeding $10 to 12 billion.”
LP-184 is a next-generation acylfulvene that selectively targets solid tumors through its synthetically lethality. LP-184’s unique design, activated by the PTGR1 enzyme, enables the drug to inflict damage upon DNA in cancer cells without affecting normal tissues.
The open-label, phase 1/2 dose-escalation/cohort-expansion study is enrolling patients that were at least 18 years of age and had histologically or cytologically documented advanced solid tumors that were relapsed/refractory to standard treatment or for which no standard treatments were available.2
Notably, patients with a relatively high prevalence of DDR gene alterations and/or PTGR1 overexpression were preferentially enrolled onto phase 1a. Patients are also required to have an ECOG performance status of 0 or 1, adequate organ function, a life expectancy exceeding 3 months, and measurable disease per RECIST 1.1 criteria or RANO 2.0 criteria.
Exclusion criteria include exposure to anticancer therapy within 2 weeks of the first dose of the trial, a history of retinopathy or macular degeneration, or receipt of radiation within 4 weeks of the first treatment cycle.
Eligible patients enrolled onto the completed phase 1a portion were given intravenous (IV) infusions of LP-184 on days 1 and 8 of each 21-day cycle for at least 2 cycles.
The primary end points for the trial were safety and tolerability, as well as identification of the RP2D and maximum tolerated dose (MTD). Pharmacokinetic and clinical activity with LP-184 served as secondary end points.
Patients with stage IV BRCA1-mutant squamous lung cancer, CHEK2-mutant thymic carcinoma, and ATM-mutant gastrointestinal stromal tumors remained on treatment at the time of this analysis.1 Clinical benefit and meaningful tumor reductions were ongoing in these patients for more than 12 to 23 months.
The RP2D of LP-184 was determined to be 0.39 mg/kg administered on days 1 and 8 of a 21-day cycle; the MTD was not reported. Of note, therapeutic plasma concentrations were achieved 3 dose levels below RP2D, indicating a wide (~2.45-fold) therapeutic window.
Additionally, over 87% of patients in phase 1a exceeded the PTGR1 bioactivation threshold, confirming its utility for patient selection.
Based on these early-phase findings, Lantern Pharma plans to initiate multiple phase 1b/2 trials of LP-184 across indications.
These trials will be guided by biomarkers and include investigations of LP-184 monotherapy in triple-negative breast cancer (TNBC) and advanced urothelial cancer; in combination with nivolumab (Opdivo) and ipilimumab (Yervoy) in non–small cell lung cancer; and in combination with spironolactone (Aldactone) in recurrent glioblastoma.
Of note, LP-184 was previously granted FDA fast track designation for glioblastoma and TNBC as well as FDA orphan drug designation in pancreatic cancer, malignant gliomas, and atypical teratoid rhabdoid tumors.
