Chengdu Chipscreen Pharmaceuticals, a subsidiary of Shenzhen-based Chipscreen Biosciences (SSE: 688321), has registered a first-in-human clinical trial for CS08399, an oral small-molecule PRMT5 inhibitor developed for patients with MTAP-deleted solid tumors and lymphoma. The Phase I study, listed on ClinicalTrials.gov as NCT07583771, is set to enroll approximately 186 adults across dose-escalation and cohort-expansion stages at Fudan University Shanghai Cancer Center in Shanghai, with recruitment expected to begin in June 2026.
Trial specifics
The NCT07583771 trial is an open-label, non-randomized, sequential Phase I study structured in two stages. The dose-escalation stage includes both single-dose and multiple-dose periods, designed to characterize the pharmacokinetic profile of CS08399 and establish its maximum tolerated dose and recommended Phase II dose. The cohort-expansion stage will then enroll additional patients at selected doses across defined tumor types, including pancreatic adenocarcinoma, non-small cell lung cancer, diffuse large B-cell lymphoma, and other advanced solid tumors carrying homozygous MTAP or CDKN2A deletion.
Primary endpoints cover safety and tolerability alongside a comprehensive pharmacokinetic assessment. Secondary endpoints address preliminary antitumor activity through objective response rate, progression-free survival, duration of response, and overall survival, with a follow-up window of up to four years.
Eligible patients must be adults with histologically or cytologically confirmed locally advanced or metastatic solid tumors, or relapsed/refractory lymphoma, whose standard therapies have failed or are no longer tolerated. Homozygous MTAP or CDKN2A deletion must be confirmed by tissue or peripheral blood testing. The trial excludes patients who have previously received MAT2A or PRMT5 inhibitors. Primary completion is projected for August 2029.
CS08399 is administered as an oral tablet, dosed once or twice daily, with dosing continuing until disease progression, intolerable toxicity, or withdrawal.
The rationale for MTAP targeting
The scientific basis for the CS08399 study rests on a well-characterized synthetic lethal relationship between MTAP deletion and PRMT5 dependence. MTAP, the gene encoding methylthioadenosine phosphorylase, is co-deleted with the tumor suppressor CDKN2A in approximately 15% of human cancers, encompassing a range of solid tumors and hematologic malignancies. When MTAP is absent, the metabolite methylthioadenosine accumulates intracellularly and acts as a partial endogenous inhibitor of PRMT5, a type II protein arginine methyltransferase involved in RNA splicing, transcriptional regulation, and cell cycle control. MTAP-deleted cells therefore operate with constitutively reduced PRMT5 activity and are thought to be more sensitive to further pharmacological inhibition of the enzyme — a dependency that normal tissues, retaining functional MTAP, do not share to the same degree.