Allarity Therapeutics Announces Phase 2 Trial of Stenoparib in Combination with Temozolomide for Recurrent Small Cell Lung Cancer Fully Funded by the US Veterans Administration
Allarity Therapeutics (NASDAQ: ALLR) has announced plans for a Phase 2 trial evaluating the combination of stenoparib with temozolomide for treating recurrent Small Cell Lung Cancer (SCLC). The trial, fully funded by the U.S. Veterans Administration through the Special Emphasis Panel on Precision Oncology, will be conducted across 11 VA medical centers.
The study will enroll approximately 65 extensive-stage SCLC patients who have failed frontline treatment. Stenoparib, a dual PARP/Wnt pathway inhibitor, combined with temozolomide aims to improve upon previous PARP inhibitor combinations that showed ~40% response rates but had dose-limiting toxicity.
Key advantages of stenoparib include its ability to cross the blood-brain barrier, potentially treating both systemic tumors and brain metastases, and its unique tankyrase inhibition affecting the Wnt pathway involved in SCLC progression and treatment resistance. The trial will assess progression-free survival and determine the recommended Phase 2 dose during an initial safety lead-in phase.
Allarity Therapeutics (NASDAQ: ALLR) ha annunciato piani per uno studio di fase 2 che valuta la combinazione di stenoparib con temozolomide per il trattamento del carcinoma polmonare a piccole cellule (SCLC) ricorrente. Lo studio, completamente finanziato dall'Amministrazione dei Veterani degli Stati Uniti attraverso il Panel di Emphasis Speciale sull'Oncologia di Precisione, sarà condotto in 11 centri medici VA.
Lo studio recluterà circa 65 pazienti con SCLC in fase avanzata che hanno fallito il trattamento di prima linea. Stenoparib, un inibitore duale della via PARP/Wnt, combinato con temozolomide mira a migliorare le precedenti combinazioni di inibitori PARP che hanno mostrato tassi di risposta del ~40% ma presentavano tossicità limitante della dose.
I principali vantaggi di stenoparib includono la sua capacità di attraversare la barriera emato-encefalica, trattando potenzialmente sia i tumori sistemici che le metastasi cerebrali, e la sua unica inibizione della tankyrase che influisce sulla via Wnt coinvolta nella progressione del SCLC e nella resistenza al trattamento. Lo studio valuterà la sopravvivenza libera da progressione e determinerà la dose raccomandata per la fase 2 durante una fase iniziale di sicurezza.
Allarity Therapeutics (NASDAQ: ALLR) ha anunciado planes para un ensayo de fase 2 que evalúa la combinación de stenoparib con temozolomida para tratar el cáncer de pulmón de células pequeñas (SCLC) recurrente. El ensayo, completamente financiado por la Administración de Veteranos de EE. UU. a través del Panel de Énfasis Especial en Oncología de Precisión, se llevará a cabo en 11 centros médicos de VA.
El estudio inscribirá aproximadamente 65 pacientes con SCLC en etapa avanzada que han fallado en el tratamiento de primera línea. Stenoparib, un inhibidor dual de la vía PARP/Wnt, combinado con temozolomida, busca mejorar las combinaciones anteriores de inhibidores de PARP que mostraron tasas de respuesta del ~40% pero presentaron toxicidad limitante de dosis.
Las principales ventajas de stenoparib incluyen su capacidad para cruzar la barrera hematoencefálica, tratando potencialmente tanto tumores sistémicos como metástasis cerebrales, y su inhibición única de tankyrase que afecta la vía Wnt involucrada en la progresión del SCLC y la resistencia al tratamiento. El ensayo evaluará la supervivencia libre de progresión y determinará la dosis recomendada para la fase 2 durante una fase inicial de seguridad.
Allarity Therapeutics (NASDAQ: ALLR)는 재발성 소세포폐암(SCLC) 치료를 위한 스텐오파립과 테모졸로마이드의 조합을 평가하는 2상 임상시험 계획을 발표했습니다. 이 시험은 정밀 온콜로지에 대한 특별 강조 패널을 통해 미국 재향군인 관리국에 의해 완전히 자금을 지원받아 11개의 VA 의료 센터에서 진행될 예정입니다.
이 연구는 1차 치료에 실패한 65명의 진행성 SCLC 환자를 모집할 예정입니다. 스텐오파립은 PARP/Wnt 경로의 이중 억제제로, 테모졸로마이드와 결합하여 약 40%의 반응률을 보였으나 용량 제한 독성이 있던 이전 PARP 억제제 조합보다 개선하는 것을 목표로 합니다.
스텐오파립의 주요 장점은 혈액-뇌 장벽을 통과할 수 있는 능력으로, 전신 종양과 뇌 전이 모두를 치료할 수 있으며, SCLC 진행 및 치료 저항성에 관여하는 Wnt 경로에 영향을 미치는 독특한 탱키레이스 억제 작용이 있습니다. 이 시험은 무진행 생존율을 평가하고 초기 안전성 주도 단계에서 2상 권장 용량을 결정할 것입니다.
Allarity Therapeutics (NASDAQ: ALLR) a annoncé des plans pour un essai de phase 2 évaluant la combinaison de stenoparib avec le temozolomide pour traiter le cancer du poumon à petites cellules (SCLC) récurrent. L'essai, entièrement financé par l'administration des anciens combattants des États-Unis à travers le panel d'emphase spéciale sur l'oncologie de précision, sera mené dans 11 centres médicaux VA.
L'étude recrutera environ 65 patients atteints de SCLC à un stade avancé qui ont échoué au traitement de première ligne. Stenoparib, un inhibiteur double de la voie PARP/Wnt, combiné avec le temozolomide, vise à améliorer les précédentes combinaisons d'inhibiteurs de PARP qui ont montré des taux de réponse d'environ 40 % mais qui présentaient une toxicité limitante de la dose.
Les principaux avantages de stenoparib comprennent sa capacité à traverser la barrière hémato-encéphalique, ce qui permet de traiter potentiellement à la fois les tumeurs systémiques et les métastases cérébrales, ainsi que son inhibition unique de la tankyrase affectant la voie Wnt impliquée dans la progression du SCLC et la résistance au traitement. L'essai évaluera la survie sans progression et déterminera la dose recommandée pour la phase 2 lors d'une phase initiale de sécurité.
Allarity Therapeutics (NASDAQ: ALLR) hat Pläne für eine Phase-2-Studie angekündigt, die die Kombination von Stenoparib mit Temozolomid zur Behandlung von rezidivierenden kleinzelligen Lungenkrebs (SCLC) bewertet. Die Studie, die vollständig von der US-Veteranenverwaltung über das Special Emphasis Panel on Precision Oncology finanziert wird, wird an 11 VA-Medizinzentren durchgeführt.
In die Studie werden voraussichtlich etwa 65 Patienten mit fortgeschrittenem SCLC aufgenommen, die in der Erstbehandlung versagt haben. Stenoparib, ein dualer PARP/Wnt-Weg-Inhibitor, kombiniert mit Temozolomid, zielt darauf ab, frühere Kombinationen von PARP-Inhibitoren zu verbessern, die eine Ansprechrate von etwa 40 % zeigten, jedoch dosislimitierende Toxizität aufwiesen.
Zu den Hauptvorteilen von Stenoparib gehört die Fähigkeit, die Blut-Hirn-Schranke zu überwinden, was potenziell sowohl systemische Tumoren als auch Hirnmetastasen behandeln kann, sowie die einzigartige Hemmung der Tankyrase, die den Wnt-Weg beeinflusst, der an der Progression von SCLC und der Behandlungresistenz beteiligt ist. Die Studie wird die progressionsfreie Überlebenszeit bewerten und die empfohlene Dosis für Phase 2 während einer anfänglichen Sicherheitsleitphase bestimmen.
- VA fully funding Phase 2 trial - no financial burden on company
- Cash position supports operations into 2026
- Drug can cross blood-brain barrier - advantage for brain metastases
- Previous PARP inhibitor combinations showed 40% response rates
- Sufficient drug supply from recent production campaign
- Still pending FDA, VA, and IRB approvals before enrollment
- Previous similar treatments showed dose-limiting toxicity
- First-time exploration of stenoparib-based combination treatment
Insights
Allarity's announcement represents a significant pipeline expansion opportunity with several strategic advantages. The Phase 2 trial exploring stenoparib combined with temozolomide for recurrent Small Cell Lung Cancer (SCLC) is fully funded by the US Veterans Administration, eliminating financial burden on Allarity while potentially expanding their market opportunity.
The combination approach addresses known challenges in SCLC treatment. Previous clinical studies showed ~40% response rates with PARP inhibitor/temozolomide combinations in recurrent SCLC, but were hampered by dose-limiting hematologic toxicity. Stenoparib's dual PARP/tankyrase inhibition mechanism provides a scientific rationale for potentially improved efficacy and safety, particularly through its unique Wnt pathway inhibition which may help overcome treatment resistance.
A important differentiator is stenoparib's ability to cross the blood-brain barrier, particularly relevant for SCLC patients who frequently present with brain metastases. This property could position stenoparib as a preferred option for this specific population.
From a development perspective, the company's existing drug supply covers this new trial without impacting their primary ovarian cancer program, demonstrating operational readiness. While regulatory approvals from FDA, VA, and IRB are still pending before enrollment begins, this external validation from the VA strengthens stenoparib's clinical development pathway without diluting shareholder value.
This VA-funded Phase 2 trial represents a capital-efficient expansion of Allarity's clinical program, particularly notable for a company with a
Strategically, this positions stenoparib beyond its current ovarian cancer focus into the SCLC market, where effective second-line treatments remain an unmet need. The dual mechanism (PARP/Wnt pathway inhibition) provides intellectual property differentiation from first-generation PARP inhibitors, potentially creating a competitive advantage if safety and efficacy endpoints are met.
The design targeting approximately 65 patients across 11 VA medical centers is appropriately sized for Phase 2 exploration, with progression-free survival as a clinically relevant endpoint. This builds on established scientific evidence supporting PARP inhibition's synergy with temozolomide, while potentially addressing the toxicity limitations that have hindered previous combination approaches.
Worth noting is that this represents Allarity's first exploration of stenoparib in a combination regimen, opening potential for additional combination studies if successful. While commercial impact remains years away, this trial could significantly enhance stenoparib's value proposition and market potential without additional capital expenditure, making this an efficiently structured opportunity to increase shareholder value through pipeline expansion.
- Trial to explore novel combination therapy for patients with recurrent Small Cell Lung Cancer who have failed frontline treatment
- Fully funded by the U.S. Veterans’ Administration Special Emphasis Panel on Precision Oncology
- Trial builds on promising clinical evidence supporting a PARP inhibitor and temozolomide combination in Small Cell Lung Cancer
Boston (March 6, 2025)—Allarity Therapeutics, Inc. (“Allarity” or the “Company”) (NASDAQ: ALLR), a Phase 2 clinical-stage pharmaceutical company dedicated to developing stenoparib—a differentiated dual PARP/Wnt pathway inhibitor—today announced plans for a Phase 2 trial evaluating the combination of stenoparib with temozolomide, a DNA-alkylating chemotherapy agent, for the treatment of recurrent Small Cell Lung Cancer (SCLC). The trial is fully funded by the U.S. Veterans Administration (VA) through the Special Emphasis Panel on Precision Oncology and is being led by the VA and Academic Medical Oncologists at Indianapolis and Pittsburgh VA Medical Centers.
This phase 2 trial builds on the compelling mechanistic synergy of temozolomide with a PARP inhibitor and selection of patients most likely to respond to this combination. Prior clinical studies had shown that PARP inhibitors combined with temozolomide provide clinical benefit as evidenced by ~
Stenoparib, a novel dual PARP and tankyrase inhibitor, may offer a more favorable tolerability profile while providing additional therapeutic advantages. Its inhibition of PARP prevents DNA repair, possibly increasing temozolomide-induced cancer cell death, while its tankyrase inhibition uniquely impacts the Wnt pathway, which is known to be implicated in SCLC progression and treatment resistance. Given these properties, stenoparib could provide a next-generation approach to overcoming temozolomide resistance while potentially avoiding the severe toxicity observed with other PARP inhibitors when combined with temozolomide.
This phase 2 study aims to evaluate the safety and efficacy of stenoparib in combination with temozolomide to determine whether this approach could offer improved therapeutic options for SCLC patients who have relapsed following frontline therapy, a population with a dire need for additional treatment options. Moreover, many patients with metastatic SCLC present with brain metastases. Importantly, stenoparib can cross the blood brain barrier, making it a promising option for treating both systemic tumors and brain metastases.
Thomas Jensen, CEO of Allarity Therapeutics, stated, “We are excited to see stenoparib being investigated in additional cancer indications, especially this trial for recurrent SCLC, a patient population with a significant unmet medical need. This trial fits perfectly with our long-term strategy for stenoparib- to leverage the unique clinical benefit we have seen from stenoparib in advanced ovarian cancer for additional cancer indications and our deeper appreciation of its differentiated mechanism of therapeutic action. Given the safety profile of stenoparib we have seen thus far, this study—the first to explore a stenoparib-based combination treatment—may help to establish stenoparib as the PARP inhibitor of choice for therapeutic combinations. This study will further allow Allarity to build out the stenoparib franchise and to drive enterprise value for the whole of Allarity Therapeutics. Importantly, our recently completed drug product campaign more than covers the amount of stenoparib needed for our clinical plans in ovarian cancer, in this combination trial and in others.”
Clinical Study Design
The trial is expected to enroll approximately 65 extensive-stage SCLC patients on the drug combination treatment across 11 VA medical centers. It will assess progression-free survival, as well as determine the recommended Phase 2 dose for the combination in an initial safety lead-in phase.
Clinical Study Rationale
Stenoparib is a dual PARP/tankyrase inhibitor that blocks DNA repair, making tumor cells more susceptible to DNA-damaging agents like temozolomide. Its tankyrase inhibition also affects the Wnt signaling pathway, which is linked to SCLC progression and treatment resistance, setting stenoparib apart from first-generation PARP inhibitors.
Temozolomide is an oral chemotherapy drug that damages tumor DNA, leading to cell death. However, resistance can develop through the MGMT enzyme, which repairs DNA damage, and mismatch repair (MMR) deficiency, which allows tumors to tolerate the drug. This study will assess whether stenoparib’s dual mechanism can help overcome resistance by disrupting key DNA repair pathways and targeting Wnt signaling.
Regulatory Status and Next Steps
Investigators are in the process of obtaining final regulatory approvals for this stenoparib-temozolomide combination trial from the U.S. Food and Drug Administration (FDA), the VA, and the Institutional Review Board (IRB) before patient enrollment can be initiated..
Funding and Financial Considerations
As previously disclosed on November 14, 2024, Allarity’s cash position supports operations into 2026. Since this Phase 2 trial of stenoparib in combination with temozolomide for recurrent SCLC is fully funded by the VA, it will not impact Allarity’s financial outlook, its Phase 2 program in advanced ovarian cancer, or its share repurchase plan.
About Stenoparib
Stenoparib is an orally available, small-molecule dual-targeted inhibitor of PARP1/2 and tankyrase 1/2. At present, tankyrases are attracting significant attention as emerging therapeutic targets for cancer, principally due to their role in regulating the Wnt signaling pathway. Aberrant Wnt/β-catenin signaling has been implicated in the development and progression of numerous cancers. By inhibiting PARP and blocking Wnt pathway activation, stenoparib’s unique therapeutic action shows potential as a promising therapeutic for many cancer types, including ovarian cancer. Allarity has secured exclusive global rights for the development and commercialization of stenoparib, which was originally developed by Eisai Co. Ltd. and was formerly known under the names E7449 and 2X-121.
About Temozolomide
Temozolomide is an orally available, small-molecule alkylating agent used as the standard-of-care chemotherapy for glioblastoma multiforme and other high-grade brain tumors. As a DNA-methylating agent, temozolomide exerts its cytotoxic effect by inducing DNA damage, primarily through the formation of O6-methylguanine adducts, which trigger cell death in tumor cells lacking functional O6-methylguanine-DNA methyltransferase (MGMT) repair activity. Due to its ability to cross the blood-brain barrier, temozolomide remains one of the few effective systemic therapies for central nervous system malignancies. Originally developed by researchers at Aston University, temozolomide was later licensed by Schering-Plough (now part of Merck & Co.) and has been commercially available since 1999 under the brand name Temodar® (Temodal® outside the U.S.).
About Allarity Therapeutics
Allarity Therapeutics, Inc. (NASDAQ: ALLR) is a clinical-stage biopharmaceutical company dedicated to developing personalized cancer treatments. The Company is focused on development of stenoparib, a novel PARP/tankyrase inhibitor for advanced ovarian cancer patients, using its DRP® technology to develop a companion diagnostic that can be used to select those patients expected to derive the greatest clinical benefit from stenoparib. Allarity is headquartered in the U.S., with a research facility in Denmark, and is committed to addressing significant unmet medical needs in cancer treatment. For more information, visit www.allarity.com.
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Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements provide the Company’s current expectations or forecasts of future events. The words “anticipates,” “believe,” “continue,” “could,” “estimate,” “expect,” “intends,” “may,” “might,” “plan,” “possible,” “potential,” “predicts,” “project,” “should,” “would” and similar expressions may identify forward-looking statements, but the absence of these words does not mean that a statement is not forward-looking. These forward-looking statements include, but are not limited to, statements regarding the investigator-initiated Phase 2 trial evaluating stenoparib in combination with temozolomide for recurrent SCLC, its potential to inform future clinical development, and the ongoing regulatory process associated with the study.
Any forward-looking statements in this press release are based on management’s current expectations of future events and are subject to multiple risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks related to the successful execution and outcomes of the Phase 2 trial, potential future clinical development of stenoparib in SCLC, securing necessary regulatory approvals, and other operational and financial risks that could impact the Company’s ability to achieve its goals. For a discussion of other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in our Form S-1/A registration statement filed on April 17, 2024, our Form 10-K annual report on file with the Securities and Exchange Commission (the “SEC”) and our Form 10-Q quarterly report filed with the SEC on November 14, 2024, available at the SEC’s website at www.sec.gov, and as well as discussions of potential risks, uncertainties and other important factors in the Company’s subsequent filings with the SEC. All information in this press release is as of the date of the release, and the Company undertakes no duty to update this information unless required by law.
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Company Contact:
investorrelations@allarity.com
Media Contact:
Thomas Pedersen
Carrotize PR & Communications
+45 6062 9390
tsp@carrotize.com
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FAQ
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