Oncternal Therapeutics Announces Updated Safety and Efficacy Data for Phase 1/2 Study of ONCT-534 for the Treatment of R/R Metastatic Castration-Resistant Prostate Cancer
Oncternal Therapeutics (Nasdaq: ONCT) has released updated data from its Phase 1/2 Study of ONCT-534 for relapsed or refractory metastatic Castration-Resistant Prostate Cancer (mCRPC). The study included 15 patients receiving once-daily (QD) dosing and 6 patients receiving twice-daily (BID) dosing. Key findings include:
1. BID dosing was well-tolerated with no related Grade 3 or higher toxicities.
2. One patient showed a 50% PSA reduction and 16% reduction in target lesions after four weeks of 300 mg BID dosing.
3. Promising effects on androgen receptor (AR)-regulated genes and AR nuclear translocation were observed in six additional patients.
4. Some non-responders showed neuroendocrine features associated with AR-independent disease.
Despite discontinuing the ONCT-534-101 trial, the company sees potential in exploring BID dosing and earlier therapy lines for advanced prostate cancer. Oncternal continues to explore strategic alternatives for its product candidates.
Oncternal Therapeutics (Nasdaq: ONCT) ha pubblicato dati aggiornati dal suo studio di Fase 1/2 su ONCT-534 per il cancro alla prostata metastatico resistente alla castrazione (mCRPC) in fase di recidiva o refrattario. Lo studio ha incluso 15 pazienti che hanno ricevuto dosaggi giornalieri (QD) e 6 pazienti che hanno ricevuto dosaggi due volte al giorno (BID). I risultati chiave includono:
1. Il dosaggio BID è stato ben tollerato, senza tossicità di grado 3 o superiore correlate.
2. Un paziente ha mostrato una riduzione del PSA del 50% e una riduzione del 16% delle lesioni target dopo quattro settimane con dosaggio di 300 mg BID.
3. Effetti promettenti sui geni regolati dai recettori androgeni (AR) e sulla traslocazione nucleare AR sono stati osservati in sei pazienti aggiuntivi.
4. Alcuni non rispondenti hanno mostrato caratteristiche neuroendocrine associate a malattia indipendente dai recettori androgeni.
Nonostante la sospensione dello studio ONCT-534-101, l'azienda vede potenziale nell'esplorare dosaggi BID e linee di terapia precoci per il cancro alla prostata avanzato. Oncternal continua a esplorare alternative strategiche per i suoi candidati terapeutici.
Oncternal Therapeutics (Nasdaq: ONCT) ha publicado datos actualizados de su estudio de Fase 1/2 sobre ONCT-534 para el cáncer de próstata resistente a la castración metastatico (mCRPC) en recaída o refractario. El estudio incluyó a 15 pacientes que recibieron dosis diarias (QD) y a 6 pacientes que recibieron dosis dos veces al día (BID). Los hallazgos clave incluyen:
1. La dosificación BID fue bien tolerada, sin toxicidades relacionadas de grado 3 o superior.
2. Un paciente mostró una reducción del PSA del 50% y una reducción del 16% en las lesiones objetivo después de cuatro semanas de dosificación de 300 mg BID.
3. Se observaron efectos prometedores en los genes regulados por el receptor de andrógenos (AR) y en la translocación nuclear de AR en seis pacientes adicionales.
4. Algunos no respondedores mostraron características neuroendocrinas asociadas con una enfermedad independiente del AR.
A pesar de haber interrumpido el ensayo ONCT-534-101, la empresa ve potencial en explorar la dosificación BID y líneas de terapia más tempranas para el cáncer de próstata avanzado. Oncternal sigue explorando alternativas estratégicas para sus candidatos a productos.
온크털널 테라퓨틱스(Nasdaq: ONCT)는 재발성 또는 내성 전이성 남성호르몬 저하 전립선암(mCRPC)에 대한 ONCT-534의 1/2상 연구 업데이트 데이터를 발표했습니다. 이 연구는 하루 한 번(QD) 복용하는 15명의 환자와 하루 두 번(BID) 복용하는 6명의 환자를 포함했습니다. 주요 발견 사항은 다음과 같습니다:
1. BID 복용이 잘 견디며 관련된 3등급 이상의 독성이 없었습니다.
2. 한 환자가 300 mg BID 복용 후 4주 만에 PSA 수치가 50% 감소하고 목표 병변이 16% 줄어들었습니다.
3. 추가로 여섯 명의 환자에서 안드로겐 수용체(AR) 조절 유전자와 AR 핵 전이의 유망한 효과가 관찰되었습니다.
4. 일부 비반응자는 AR 독립 질병과 관련된 신경내분비 특징을 보였습니다.
ONCT-534-101 시험을 중단했음에도 불구하고 회사는 전이성 전립선암에 대한 BID 복용과 더 이른 치료 절차 심화 가능성을 보고 있습니다. 온크털널은 제품 후보에 대한 전략적 대안을 탐색하고 있습니다.
Oncternal Therapeutics (Nasdaq: ONCT) a publié des données mises à jour de son étude de phase 1/2 sur ONCT-534 pour le cancer de la prostate métastatique résistant à la castration (mCRPC) en rechute ou réfractaire. L'étude a inclus 15 patients recevant une dose quotidienne (QD) et 6 patients recevant une dose deux fois par jour (BID). Les principales conclusions comprennent :
1. Le dosage BID a été bien toléré, sans toxicités de grade 3 ou supérieur liées.
2. Un patient a montré une réduction du PSA de 50 % et une réduction de 16 % des lésions cibles après quatre semaines de dosage de 300 mg BID.
3. Des effets prometteurs sur les gènes régulés par le récepteur aux androgènes (AR) et la translocation nucléaire de AR ont été observés chez six patients supplémentaires.
4. Certains non-répondants ont présenté des caractéristiques neuroendocrines associées à une maladie indépendante des AR.
Bien que l'essai ONCT-534-101 ait été interrompu, l'entreprise voit un potentiel dans l'exploration du dosage BID et des lignes de traitement plus précoces pour le cancer de la prostate avancé. Oncternal continue d'explorer des alternatives stratégiques pour ses candidats de produits.
Oncternal Therapeutics (Nasdaq: ONCT) hat aktualisierte Daten aus seiner Phase 1/2-Studie zu ONCT-534 für rezidivierenden oder refraktären metastatischen kastrationsresistenten Prostatakrebs (mCRPC) veröffentlicht. Die Studie umfasste 15 Patienten, die einmal täglich (QD) und 6 Patienten, die zweimal täglich (BID) behandelt wurden. Wesentliche Ergebnisse sind:
1. Die BID-Dosierung wurde gut vertragen, ohne damit verbundene Grad-3- oder höheren Toxizitäten.
2. Ein Patient zeigte nach vier Wochen mit einer Dosis von 300 mg BID eine Reduktion des PSA um 50% und eine Reduktion der Zielverletzungen um 16%.
3. In sechs weiteren Patienten wurden vielversprechende Effekte auf androgenregulierte Gene (AR) sowie AR-nukleäre Translokation beobachtet.
4. Einige Nicht-Responder zeigten neuroendokrine Merkmale, die mit AR-unabhängiger Krankheit assoziiert sind.
Trotz der Einstellung der ONCT-534-101-Studie sieht das Unternehmen Potenzial in der Erforschung der BID-Dosierung und früherer Therapieansätze für fortgeschrittenen Prostatakrebs. Oncternal prüft weiterhin strategische Alternativen für seine Produktkandidaten.
- BID dosing of ONCT-534 was well-tolerated with no related Grade 3 or higher toxicities
- One patient showed 50% PSA reduction and 16% reduction in target lesions after 4 weeks of 300 mg BID dosing
- Promising effects observed on androgen receptor-regulated genes and AR nuclear translocation in six additional patients
- Decision to discontinue the ONCT-534-101 clinical trial remains in place
- Some patients who did not respond to ONCT-534 had prostate cancer with neuroendocrine features, indicating AR-independent disease
Insights
The updated data from Oncternal's Phase 1/2 study of ONCT-534 for mCRPC shows promising signs but requires cautious interpretation. The twice-daily (BID) dosing appears well-tolerated with no related Grade 3 or higher toxicities, which is positive for safety. The 50% PSA reduction and 16% tumor shrinkage in one patient at 300 mg BID is encouraging, suggesting potential efficacy at higher doses.
The circulating tumor cell (CTC) analysis provides valuable insights into the drug's mechanism of action, showing effects on AR-regulated genes and AR nuclear translocation. However, the discovery of neuroendocrine features in non-responding patients highlights a potential limitation and the need for patient selection strategies.
While the company has discontinued the trial, these results suggest ONCT-534 may have value in earlier treatment lines or with optimized dosing. The decision to explore strategic alternatives for their pipeline assets indicates financial constraints rather than lack of potential, which is common in the current biotech landscape.
Oncternal's decision to discontinue the ONCT-534-101 trial despite promising data reflects the challenging financial environment for small biotech companies. With a market cap of only
The focus on "maximizing value to shareholders" through exploring strategic alternatives suggests potential asset sales, partnerships, or even a company sale. This approach could unlock value in their pipeline, including ONCT-534, ONCT-808, zilovertamab and ONCT-216.
Investors should note that while the clinical data is encouraging, the company's financial situation creates significant uncertainty. Any partnerships or asset sales could provide near-term catalysts, but the terms and timing are unknown. The stock remains highly speculative, with potential for significant upside if a favorable deal is reached, but also substantial downside risk if no value-realizing transactions materialize.
SAN DIEGO, Oct. 22, 2024 (GLOBE NEWSWIRE) -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT) (the “Company”) today announced updated data from its Phase 1/2 Study of ONCT-534 for the treatment of patients with relapsed or refractory metastatic Castration-Resistant Prostate Cancer (mCRPC).
Based on initial pharmacokinetic results, two additional dosing cohorts with twice daily (BID) oral dosing of ONCT-534 had been incorporated in the Phase 1/2 study ONCT-534-101 (NCT05917470). Overall, fifteen patients received ONCT-534 once daily (QD) in six dosing cohorts and six patients received ONCT-534 BID in two dosing cohorts. Based on a data cut off of September 30, 2024, the BID dosing schedule was well tolerated, with no related Grade 3 or higher toxicities. One patient, who experienced a rising PSA on ONCT-534 at 160 mg BID, had a subsequent
“While we still believe the decision to discontinue the ONCT-534-101 clinical trial remains the correct one in the current biotechnology environment, the updated clinical results highlight the potential of ONCT-534 in prostate cancer. We believe there is value in exploring BID dosing further, as well as studying ONCT-534 in earlier lines of therapy for advanced prostate cancer,” said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. “We continue to explore strategic alternatives for our product candidates, including ONCT-534, ONCT-808, zilovertamab and ONCT-216 in an ongoing effort to maximize value to our shareholders.”
About Oncternal Therapeutics
Oncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of patients with cancers that have critical unmet medical need. Oncternal pursues drug development targeting promising, yet untapped biological pathways implicated in cancer generation or progression, focusing on hematological malignancies and prostate cancer. More information on our company and programs is available at https://oncternal.com/.
About ONCT-534
ONCT-534 is an investigational dual-action androgen receptor inhibitor (DAARI) with demonstrated preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR mutation and aberration. It is a potential treatment for patients with mCRPC with unmet medical need because of resistance to androgen receptor pathway inhibitors, including those with AR amplification, mutations in the AR ligand binding domain (LBD), or splice variants with loss of the AR LBD. It was investigated in Study ONCT-534-101 (NCT05917470) for the treatment of patients with mCRPC who are resistant to current AR pathway inhibitors.
About ONCT-808
ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using the binding domain from zilovertamab. ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1. Oncternal has developed a robust and reproducible manufacturing process that has the potential to reduce the time patients must wait for their individual CAR T therapy to be produced compared with currently approved CAR T products. It was investigated in Study ONCT-808-101 (NCT05588440) with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment.
About zilovertamab
Zilovertamab (previously called cirmtuzumab and UC-961) is an investigational monoclonal antibody designed to inhibit the function of Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1). Zilovertamab has been evaluated in Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL), which resulted in
About ONCT-216
ONCT-216 (previously called TK216) is an investigational targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins including fusion proteins. Tumorigenic fusion proteins involving the EWS protein and an ETS protein can be found in most cases of Ewing sarcoma. ETS-related translocations or overexpression are also found in many other tumors such as acute myeloid leukemia (AML), diffuse large B cell lymphoma (DLBCL), and prostate cancer. In preclinical models, ONCT-216 was observed to bind to EWS-FLI1, blocking the interaction between this fusion protein and other transcriptome proteins such as RNA helicase A, leading to tumor cell apoptosis and inhibiting tumor growth in animal models. The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation, Orphan Drug Designation and Fast Track Status to ONCT-216 for the treatment of Ewing sarcoma. The results of a Phase 1/ 2 clinical trial of ONCT-216 in patients with Ewing sarcoma (NCT02657005) were recently published (Myers 2024).
Forward-Looking Information
Oncternal cautions you that statements included in this press release that are not a description of historical facts are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negatives of these terms or other similar expressions. These statements are based on Oncternal’s current beliefs and expectations. Forward-looking statements include statements regarding: Oncternal’s ability to complete a strategic transaction or continue as a going concern even if a strategic transaction is completed; anticipated benefits of strategic transactions; Oncternal’s ability to preserve cash during the strategic alternatives process; and the potential of ONCT-534. Forward-looking statements are subject to risks and uncertainties inherent in Oncternal’s business, including: Oncternal may not realize the benefits expected from the workforce reduction and discontinuation of product development activities, including its ability to conserve cash; Oncternal’s ability to retain remaining key personnel; whether Oncternal will be able to secure and complete or achieve the anticipated benefits from any potential strategic transactions on acceptable terms or at all; Oncternal may use its capital resources sooner than it anticipates, resulting in a liquidation and dissolution of the Company; Oncternal’s common stock may be delisted from Nasdaq; and other risks described in Oncternal’s filings with the U.S. Securities and Exchange Commission. All forward-looking statements in this press release are current only as of the date hereof and, except as required by applicable law, Oncternal undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
Contact Information:
Investors
Richard Vincent
858-434-1113
rvincent@oncternal.com
Business Development
Pablo Urbaneja
415-316-8276
purbaneja@oncternal.com
FAQ
What were the key findings from Oncternal's Phase 1/2 study of ONCT-534 for mCRPC?
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What type of cancer is ONCT-534 being developed to treat?
