Aprea Therapeutics Presents Preliminary Findings on Oral WEE1 Inhibitor APR-1051 at EORTC-NCI-AACR International Conference on Molecular Targets and Therapeutics
Aprea Therapeutics (APRE) presented preliminary safety results for its WEE1 inhibitor APR-1051 at the EORTC-NCI-AACR Symposium. The Phase 1 ACESOT-1051 trial is evaluating APR-1051 as monotherapy in advanced solid tumors. Data from two of three enrolled patients show the drug is safe and well-tolerated with no hematologic toxicity. All adverse events were Grade 1 and 2, with no QT prolongation observed. The trial is actively enrolling at three U.S. sites, with planned doses ranging from 10mg to 150mg daily. The study consists of two parts: dose escalation (up to 39 patients) and dose optimization (up to 40 patients).
Aprea Therapeutics (APRE) ha presentato risultati preliminari di sicurezza per il suo inibitore WEE1 APR-1051 al Simposio EORTC-NCI-AACR. Il trial di Fase 1 ACESOT-1051 sta valutando APR-1051 come monoterapia in tumori solidi avanzati. I dati di due dei tre pazienti arruolati mostrano che il farmaco è sicuro e ben tollerato, senza tossicità ematologica. Tutti gli eventi avversi sono stati di Grado 1 e 2, senza prolungamento del QT osservato. Il trial è attivamente in fase di reclutamento in tre siti statunitensi, con dosi pianificate che vanno da 10 mg a 150 mg al giorno. Lo studio è composto da due parti: escalation della dose (fino a 39 pazienti) e ottimizzazione della dose (fino a 40 pazienti).
Aprea Therapeutics (APRE) presentó resultados preliminares de seguridad para su inhibidor WEE1 APR-1051 en el Simposio EORTC-NCI-AACR. El ensayo de Fase 1 ACESOT-1051 está evaluando APR-1051 como monoterapia en tumores sólidos avanzados. Los datos de dos de los tres pacientes inscritos muestran que el medicamento es seguro y bien tolerado, sin toxicidad hematológica. Todos los eventos adversos fueron de Grado 1 y 2, sin observarse prolongación del QT. El ensayo está reclutando activamente en tres sitios en EE. UU., con dosis planificadas que varían de 10 mg a 150 mg diarios. El estudio consta de dos partes: escalamiento de dosis (hasta 39 pacientes) y optimización de dosis (hasta 40 pacientes).
Aprea Therapeutics (APRE)는 EORTC-NCI-AACR 심포지엄에서 WEE1 억제제 APR-1051의 초기 안전성 결과를 발표했습니다. 1상 ACESOT-1051 시험은 진전된 고형 종양에서 APR-1051 단독 요법을 평가하고 있습니다. 등록된 세 환자 중 두 환자의 데이터는 약물이 안전하고 잘 견딜 수 있으며 혈액학적 독성이 없음을 보여줍니다. 모든 부작용은 1등급과 2등급이었으며 QT 연장 현상은 관찰되지 않았습니다. 이 시험은 미국의 세 곳에서 활발히 환자를 모집 중이며, 계획된 용량은 하루 10mg에서 150mg까지 다양합니다. 이 연구는 용량 증가(최대 39명 환자)와 용량 최적화(최대 40명 환자) 두 부분으로 구성됩니다.
Aprea Therapeutics (APRE) a présenté des résultats préliminaires de sécurité pour son inhibiteur WEE1 APR-1051 lors du Symposium EORTC-NCI-AACR. L'essai de Phase 1 ACESOT-1051 évalue APR-1051 en tant que monothérapie dans des tumeurs solides avancées. Les données de deux des trois patients inscrits montrent que le médicament est sûr et bien toléré, sans toxicité hématologique. Tous les événements indésirables étaient de Grade 1 et 2, sans prolongation du QT observée. L'essai recrute activement sur trois sites aux États-Unis, avec des doses prévues allant de 10 mg à 150 mg par jour. L'étude se compose de deux parties : l'escalade des doses (jusqu'à 39 patients) et l'optimisation des doses (jusqu'à 40 patients).
Aprea Therapeutics (APRE) hat vorläufige Sicherheitsdaten für seinen WEE1-Inhibitor APR-1051 auf dem EORTC-NCI-AACR-Symposium vorgestellt. Die Phase-1-Studie ACESOT-1051 bewertet APR-1051 als Monotherapie bei fortgeschrittenen soliden Tumoren. Daten von zwei der drei eingeschlossenen Patienten zeigen, dass das Medikament sicher und gut verträglich ist, ohne hämatologische Toxizität. Alle unerwünschten Ereignisse waren Grad 1 und 2, ohne beobachtete QT-Verlängerung. Die Studie rekrutiert aktiv an drei Standorten in den USA, mit geplanten Dosierungen von 10 mg bis 150 mg täglich. Die Studie besteht aus zwei Teilen: Dosissteigerung (bis zu 39 Patienten) und Dosisoptimierung (bis zu 40 Patienten).
- Preliminary safety data shows APR-1051 is well-tolerated with no significant adverse effects
- No hematologic toxicity observed in initial patients
- Stable or increased hemoglobin, hematocrit, and platelet counts during first treatment cycle
- One patient had disease progression at 49 days
- Second patient withdrew after 36 days of treatment
- Currently testing only subtherapeutic doses (10-30mg)
Insights
The preliminary Phase 1 clinical trial results for APR-1051 show promising safety data, though at subtherapeutic doses. The key differentiator is the absence of hematologic toxicity and QT prolongation - common issues with other WEE1 inhibitors. The data from just 2 patients at low doses (10-30mg) is too to draw meaningful conclusions about efficacy, with one patient progressing at 49 days and another withdrawing at 36 days.
The trial design targeting up to 39 patients in Part 1 and 40 patients in Part 2 is robust. The planned dose escalation to 150mg will be critical in determining therapeutic potential. While the safety profile appears favorable compared to competitors, efficacy data expected in 2025 will be essential to validate APR-1051's potential market position.
Phase 1 ACESOT-1051 clinical trial is evaluating APR-1051 as monotherapy treatment in patients with significant unmet medical need; active enrollment is ongoing at three sites in the U.S.
Preliminary results to date demonstrate APR-1051 is safe and well-tolerated with no hematologic toxicity
DOYLESTOWN, Pa., Oct. 23, 2024 (GLOBE NEWSWIRE) -- Aprea Therapeutics, Inc. (Nasdaq: APRE) (“Aprea”, or the “Company”), a clinical-stage biopharmaceutical company focused on precision oncology through synthetic lethality, today announced that preliminary safety results on its WEE1 inhibitor APR-1051 are highlighted in a poster being presented today at the EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics, taking place in Barcelona, Spain.
The results are from ACESOT-1051, a first-in-human Phase 1 study assessing the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations.
The dose escalation part of the study (Part 1) is currently ongoing and is expected to include up to 39 patients with advanced solid tumors. Oral APR-1051 is being administered once daily for 28-day cycles. A total of 8 cohorts are planned, evaluating doses of 10 mg to 150 mg once daily. So far, patients have been enrolled in single patient Cohorts 1, 2 and 3, evaluating subtherapeutic doses of 10 mg, 20 mg and 30 mg, respectively.
Preliminary results
Data are available on two of three patients, with a cutoff date of October 7, 2024
- Preliminary results demonstrate that APR-1051 is safe and well-tolerated with no hematologic toxicity
- Hemoglobin, hematocrit, and platelet counts were stable or increased slightly during the first treatment cycle
- There were no signs of neutropenia, with white blood cells and neutrophils trending up for both patients during the first treatment cycle
- All adverse events (AEs) recorded were Grade 1 and 2, with one Grade 1 AE (abdominal distention) possibly related to APR-1051
- No QT prolongation has been observed
- Three patients have been dosed to date with data available on two of these. One had disease progression at 49 days, a second withdrew following 36 days of treatment and dosing is ongoing in the third patient.
“These preliminary data from our ongoing Phase 1 study are encouraging, showing that APR-1051 is safe and well-tolerated,” said Philippe Pultar, MD, Senior Medical Advisor and Lead of WEE1 Clinical Development at Aprea. “APR-1051 has been designed to be selective for WEE1, without the off-target inhibition of PLK or QT prolongation reported for other molecules in this class. We expect to confirm this favorable safety profile as we move to higher doses in the ACESOT-1051 trial. We are excited to explore the full therapeutic benefits of APR-1051, which has best in class potential, and hope to generate preliminary efficacy data from the study during 2025.”
APR-1051 targets WEE1 kinase, an enzyme involved in the DNA damage response pathway. Based on preclinical studies, Aprea believes that APR-1051 may solve liabilities associated with other WEE1 inhibitors and is differentiated based on: 1) molecular structure; 2) selectivity for WEE1 versus off-target inhibition of the polo-like kinase, or PLK, family of kinases; 3) potentially improved pharmacokinetic (PK) properties; and 4) potential absence of QT prolongation at doses that significantly inhibit WEE1. No head-to-head studies with APR-1051 have been conducted.
Active enrollment in ACESOT-1051 is ongoing at three sites in the U.S. (NEXT Oncology locations in San Antonio and Dallas, and The University of Texas MD Anderson Cancer Center) with planned additional sites.
Anthony Tolcher M.D., Founder of Next Oncology commented, “The preliminary findings from ACESOT-1051 are promising and we are encouraged by the minimal toxicity in the patients treated so far. WEE1 kinase is a validated oncology target and represents an opportunity for therapeutic intervention in patients who otherwise have poor prognosis and no effective treatments today. We look forward to further exploring APR-1051's potential and are excited to recruit additional patients as the study progresses.”
ACESOT-1051 Study Design
ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) is a focused biomarker-driven study designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. Oral APR-1051 will be administered once daily for 28-day cycles. The study consists of two parts: Part 1 is dose escalation and is expected to enroll up to 39 patients with advanced solid tumors. The first three dose levels are using accelerated titration followed by Bayesian Optimal Interval (BOIN) design for the remaining dose levels; Part 2 (up to 40 patients) is designed for dose optimization, with the goal of selecting the Recommended Phase 2 Dose (RP2D). For more information, refer to Clinicaltrials.gov: NCT06260514.
A copy of the poster will be available on Aprea’s corporate website today. Three additional posters will be available at the conclusion of the EORTC-NCI-AACR Symposium on Friday, October 25, 2024.
About Aprea
Aprea Therapeutics, Inc. is a clinical-stage biopharmaceutical company headquartered in Doylestown, Pennsylvania, focused on precision oncology through synthetic lethality. The Company’s lead program is ATRN-119, a clinical-stage small molecule ATR inhibitor in development for solid tumor indications. APR-1051, an oral, small molecule WEE1 inhibitor, recently entered the clinic. For more information, please visit the company website at www.aprea.com.
The Company may use, and intends to use, its investor relations website at https://ir.aprea.com/ as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD.
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FAQ
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