Aprea Therapeutics Reports Second Partial Response for WEE1 Inhibitor APR-1051 in Phase 1 Endometrial Cancer Trial
核心洞察
Aprea Therapeutics' WEE1 (搜索) inhibitor APR-1051 achieved two unconfirmed partial responses in endometrial cancer (搜索) patients with PPP2R1A (搜索) mutations at 150 mg and 220 mg dose levels.
The Phase 1 ACESOT-1051 trial has enrolled 22 patients across multiple solid tumor types, with five additional patients achieving stable disease.
APR-1051 demonstrated favorable tolerability and potential dose-response trends across genomically defined cancers, supporting continued clinical development.
Aprea Therapeutics has announced promising clinical activity for its WEE1 (搜索) inhibitor APR-1051, with a second partial response observed in the ongoing Phase 1 ACESOT-1051 trial. The company reported that two patients with endometrial cancer (搜索) harboring PPP2R1A (搜索) mutations achieved unconfirmed partial responses at their first scan, observed at the 150 mg and 220 mg dose levels respectively.
Clinical Activity Across Multiple Tumor Types
The ACESOT-1051 trial has treated 22 patients to date at doses ranging from 10 mg to 220 mg. Beyond the two partial responses in endometrial cancer (搜索), five additional patients achieved stable disease across various solid tumor types:
- At 70 mg: One patient with HPV-positive head and neck squamous cell carcinoma (HNSCC)
- At 100 mg: Three patients including FBXW7-mutated colon cancer, KRAS & p53-mutated colon cancer, and CCNE1 & TP53 mutated uterine cancer
- At 150 mg: One patient with FBXW7-mutated colon cancer
The first partial response patient, treated at 150 mg, achieved a 50% reduction in target lesion size per RECIST v1.1 criteria and experienced a marked reduction in cancer antigen 125 (CA-125) levels from 732 to 70 U/mL. Earlier cohorts showed tumor burden reductions including a 5% reduction at 70 mg in HPV-positive HNSCC and a 15% reduction in FBXW7 (搜索)-mutated colon cancer (搜索) at 100 mg, with one patient remaining on therapy for over 210 days.
Targeting Genomic Vulnerabilities
APR-1051 is designed to exploit cancer-specific vulnerabilities while minimizing damage to healthy cells. The drug targets cancers with specific genomic alterations, including HPV-positive disease and mutations in PPP2R1A (搜索), FBXW7 (搜索), CCNE1 (搜索), TP53 (搜索), and KRAS (搜索) genes.
"These early single-agent data demonstrate that APR-1051 has clinical activity as a single agent," said Anthony Tolcher, MD, FRCPC, Principal Investigator at Next Oncology. "The observation of a partial response on the first scan, together with a decrease in tumor marker at this dose level, supports continued clinical evaluation of APR-1051."
Trial Design and Future Plans
The ACESOT-1051 study is a first-in-human, open-label Phase 1 trial evaluating safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in patients with advanced solid tumors. The dose-escalation portion expects to enroll up to 50 patients across nine planned dose cohorts, ranging from 10 mg to 300 mg administered once daily in continuous 28-day cycles.
APR-1051 has been generally well tolerated across all dose levels tested. Enrollment in the 220 mg dose cohort continues, and the company plans to expand enrollment of PPP2R1A (搜索) endometrial and HPV-positive HNSCC patients within the study.
Oren Gilad, PhD, Chief Executive Officer of Aprea Therapeutics, noted, "These preliminary results provide early proof-of-concept for single-agent activity of APR-1051 and support our strategy of targeting cancers with specific genomic alterations. The potential dose-response trend and favorable safety profile observed in the ongoing dose-escalation study reinforce our confidence in the potential of APR-1051 as a differentiated WEE1 (搜索) inhibitor for patients with advanced solid tumors."
The company expects to provide additional updates in the first half of 2026 and complete dose escalation later in the year.