# A first-in-human phase 1a study of LP-184, a tumor-site activated novel alkylating agent, in patients with advanced solid tumors

Source: https://onco.cc/key-papers/paper-nct05933265-invest-new-drugs-2026/  
OnCo record `paper-nct05933265-invest-new-drugs-2026` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Published report from the trial registered as NCT05933265, in Investigational new drugs (2026), chosen as the most cited paper whose own text cites the registry id.

## Summary

LP-184 is a novel acylfulvene pro-drug that alkylates DNA after bioactivation by the intracellular oxidoreductase prostaglandin reductase 1 (PTGR1). In preclinical studies, potent growth inhibition has been observed against a wide variety of solid tumor models, particularly those carrying DNA damage repair deficiency. Here, we report results of the first-in-human dose escalation trial of LP-184 in advanced solid tumors. A dose escalation Bayesian optimal interval design was used with a starting dose of 0.01 mg/kg. Eligible patients with advanced refractory solid tumors were enrolled to receive LP-184 intravenously on days 1 and 8 of each 21-day cycle. Sixty-three patients were enrolled, with a median age of 62 years. Twelve dose levels (DLs) were evaluated with one dose-limiting toxicity (DLT) at DL11 (0.49 mg/kg; grade 4 platelet count decreased) and two DLTs at DL12 (0.61 mg/kg; grade 3 alanine aminotransferase increased and acute liver injury). The most common (≥ 20%) treatment-related adverse events of any grade included nausea, vomiting, fatigue, and platelet count decreased. No treatment-related deaths occurred during the study. Best response to monotherapy LP-184 was stable disease (SD), which was observed in 22 (40%) of the evaluable patients. Three patients experienced SD that lasted more than 12 months. LP-184 was safe and tolerable in the Phase 1a trial in patients with advanced refractory solid tumors. The maximum tolerated dose (MTD) of LP-184 is 0.49 mg/kg. Registry: ClinicalTrials.gov, TRN: NCT05933265, Registration date: June 23, 2023.

Indexed on Europe PMC as PubMed record 42410111 (DOI 10.1007/s10637-026-01626-y). Its abstract cites the registry id NCT05933265, which is how it was matched to this trial; no figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Investigational new drugs
- Year: 2026
- DOI: 10.1007/s10637-026-01626-y
- Authors: Mahadevan D, Parekh J, Beck JT, et al.
- What it means: This is the paper Europe PMC returns for registry id NCT05933265 with the most citations, so it is the natural first reading for anyone following the trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
- Caveats: Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.

## Sources

- Invest New Drugs 2026: https://doi.org/10.1007/s10637-026-01626-y
- PubMed: https://pubmed.ncbi.nlm.nih.gov/42410111/
- Europe PMC: https://europepmc.org/article/MED/42410111
- ClinicalTrials.gov NCT05933265: https://clinicaltrials.gov/study/NCT05933265

## Connected records

- trials: [Study of LP-184 in Patients With Advanced Solid Tumors](https://onco.cc/trials/nct05933265/)

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