ALX Oncology Reports ASPEN-03 and ASPEN-04 Phase 2 Trials Evaluating Evorpacept with a Checkpoint Inhibitor for the Treatment of Head and Neck Cancers Did Not Meet Primary Endpoints
ALX Oncology (ALXO) announced that its Phase 2 ASPEN-03 and ASPEN-04 clinical trials for evorpacept in combination with Merck's KEYTRUDA® did not meet primary endpoints for treating head and neck squamous cell carcinoma (HNSCC). The trials evaluated improved objective response rates compared to historical controls.
Despite encouraging trends in ASPEN-03, the company will discontinue pursuing evorpacept with pembrolizumab in HNSCC. However, ALX Oncology will continue multiple clinical trials of evorpacept combined with anti-cancer antibodies, citing positive results in HER2-positive gastric and breast cancer trials.
The company remains focused on evorpacept's primary mechanism of action - blocking the CD47 'don't eat me' signal on cancer cells - and its ongoing evaluation in colorectal cancer, breast cancer, non-Hodgkin lymphoma, and multiple myeloma trials.
ALX Oncology (ALXO) ha annunciato che i suoi studi clinici di Fase 2 ASPEN-03 e ASPEN-04 per evorpacept in combinazione con KEYTRUDA® di Merck non hanno raggiunto gli endpoint primari nel trattamento del carcinoma squamoso della testa e del collo (HNSCC). Gli studi hanno valutato un miglioramento dei tassi di risposta obiettiva rispetto ai controlli storici.
Nonostante tendenze incoraggianti in ASPEN-03, l'azienda interromperà lo sviluppo di evorpacept in combinazione con pembrolizumab per HNSCC. Tuttavia, ALX Oncology continuerà diversi studi clinici di evorpacept associato ad anticorpi anti-cancro, citando risultati positivi negli studi su tumori gastrici e mammari HER2-positivi.
L'azienda rimane concentrata sul principale meccanismo d'azione di evorpacept - il blocco del segnale CD47 "non mangiarmi" sulle cellule tumorali - e sulla sua valutazione in corso in studi su cancro colorettale, mammario, linfoma non-Hodgkin e mieloma multiplo.
ALX Oncology (ALXO) anunció que sus ensayos clínicos de Fase 2 ASPEN-03 y ASPEN-04 con evorpacept en combinación con KEYTRUDA® de Merck no alcanzaron los objetivos principales en el tratamiento del carcinoma de células escamosas de cabeza y cuello (HNSCC). Los estudios evaluaron tasas de respuesta objetiva mejoradas en comparación con controles históricos.
A pesar de tendencias alentadoras en ASPEN-03, la compañía dejará de desarrollar evorpacept junto con pembrolizumab para HNSCC. Sin embargo, ALX Oncology continuará con múltiples ensayos clínicos de evorpacept combinado con anticuerpos anticancerígenos, citando resultados positivos en estudios para cáncer gástrico y de mama HER2-positivo.
La empresa sigue enfocada en el mecanismo principal de acción de evorpacept: bloquear la señal CD47 de "no me comas" en las células cancerosas, y su evaluación continua en ensayos para cáncer colorrectal, de mama, linfoma no Hodgkin y mieloma múltiple.
ALX Oncology (ALXO)는 Merck의 KEYTRUDA®와 병용한 evorpacept의 2상 임상시험 ASPEN-03 및 ASPEN-04가 두경부 편평세포암(HNSCC) 치료에서 주요 평가 지표를 충족하지 못했다고 발표했습니다. 이 시험들은 과거 데이터 대비 객관적 반응률 개선을 평가했습니다.
ASPEN-03에서 고무적인 경향이 있었음에도 불구하고, 회사는 HNSCC에서 pembrolizumab과의 evorpacept 개발을 중단할 예정입니다. 그러나 ALX Oncology는 HER2 양성 위암 및 유방암 임상시험에서 긍정적인 결과를 바탕으로 evorpacept와 항암 항체 병용 임상시험은 계속 진행할 것입니다.
회사는 evorpacept의 주요 작용 기전인 암세포의 CD47 '먹지 마세요' 신호 차단에 집중하며, 대장암, 유방암, 비호지킨 림프종, 다발성 골수종 임상시험에서의 평가를 계속하고 있습니다.
ALX Oncology (ALXO) a annoncé que ses essais cliniques de phase 2 ASPEN-03 et ASPEN-04 pour evorpacept en association avec KEYTRUDA® de Merck n'ont pas atteint les critères principaux dans le traitement du carcinome épidermoïde de la tête et du cou (HNSCC). Les essais ont évalué une amélioration des taux de réponse objective par rapport aux contrôles historiques.
Malgré des tendances encourageantes dans ASPEN-03, la société cessera de développer evorpacept avec pembrolizumab dans le HNSCC. Toutefois, ALX Oncology poursuivra plusieurs essais cliniques d'evorpacept combiné à des anticorps anticancéreux, citant des résultats positifs dans les essais sur les cancers gastriques et du sein HER2-positifs.
L'entreprise reste concentrée sur le principal mécanisme d'action d'evorpacept – le blocage du signal CD47 « ne me mange pas » sur les cellules cancéreuses – et son évaluation en cours dans des essais sur le cancer colorectal, le cancer du sein, le lymphome non hodgkinien et le myélome multiple.
ALX Oncology (ALXO) gab bekannt, dass die Phase-2-Studien ASPEN-03 und ASPEN-04 mit evorpacept in Kombination mit Mercks KEYTRUDA® die primären Endpunkte bei der Behandlung von Plattenepithelkarzinomen im Kopf-Hals-Bereich (HNSCC) nicht erreicht haben. Die Studien bewerteten verbesserte objektive Ansprechraten im Vergleich zu historischen Kontrollen.
Trotz vielversprechender Trends in ASPEN-03 wird das Unternehmen die Entwicklung von evorpacept zusammen mit Pembrolizumab bei HNSCC einstellen. ALX Oncology wird jedoch mehrere klinische Studien mit evorpacept in Kombination mit krebsbekämpfenden Antikörpern fortsetzen, da positive Ergebnisse bei HER2-positivem Magen- und Brustkrebs vorliegen.
Das Unternehmen konzentriert sich weiterhin auf den Hauptwirkmechanismus von evorpacept – die Blockade des CD47-'Fress mich nicht'-Signals auf Krebszellen – und die laufende Prüfung in Studien zu Darmkrebs, Brustkrebs, Non-Hodgkin-Lymphom und multiplem Myelom.
- Evorpacept demonstrated manageable safety profile in combination with pembrolizumab
- Showed encouraging trends in ASPEN-03 objective response rates
- Demonstrated durable clinical responses in HER2-positive gastric and breast cancer trials
- Failed to meet primary endpoints in both ASPEN-03 and ASPEN-04 Phase 2 trials
- Company discontinuing evorpacept development for head and neck cancer with pembrolizumab
- Trial outcomes insufficient to advance to registrational trial in HNSCC
Insights
Evorpacept's failure in HNSCC trials eliminates a treatment pathway while success in antibody combinations keeps clinical development alive.
The Phase 2 ASPEN-03 and ASPEN-04 trial results represent a significant clinical setback for ALX Oncology's lead candidate evorpacept in head and neck squamous cell carcinoma. The failure to meet the primary endpoint of improved objective response rates compared to historical controls effectively closes an important potential treatment pathway for HNSCC patients, a population with effective options.
What's mechanistically noteworthy is the distinction between evorpacept's two therapeutic strategies. The drug blocks CD47, the "don't eat me" signal that cancer cells use to evade immune detection. In these failed trials, researchers explored whether evorpacept could enhance T-cell priming through dendritic cell activation when combined with pembrolizumab. However, the company's ongoing trials focus on evorpacept's primary mechanism - enhancing macrophage-mediated phagocytosis when paired with tumor-targeting antibodies like HERCEPTIN
Despite efficacy disappointments, the safety profile remains manageable with no new concerns emerging from combining evorpacept with pembrolizumab and chemotherapy. This maintained safety profile preserves evorpacept's viability for other development programs in HER2-positive gastric cancer, breast cancer, colorectal cancer, non-Hodgkin lymphoma and multiple myeloma, where the company suggests they've seen more promising activity.
Failed Phase 2 trials eliminate HNSCC indication for evorpacept, creating significant headwinds for this micro-cap biotech.
This clinical setback for ALX Oncology eliminates a significant market opportunity for their lead asset evorpacept. For a micro-cap biotech with approximately
The strategic pivot to concentrate exclusively on anti-cancer antibody combinations appears rational but substantially narrows evorpacept's addressable market. Management's mention of "encouraging trends" in ASPEN-03 suggests the results weren't catastrophically negative but fell short of commercial viability thresholds that would justify advancing to a registrational study.
ALX will now focus resources on combinations with anti-cancer antibodies, where they claim to have demonstrated "response rates and durability beyond what is expected from standard of care" across several studies. Their near-term catalysts include data readouts in breast cancer and colorectal cancer programs, which now carry increased importance for the company's prospects.
The pipeline includes some diversification with ALX2004, their EGFR-targeted antibody-drug conjugate, though minimal details were provided about its development stage. With a failed program now behind them, investor focus will intensify on the remaining clinical programs and the company's ability to deliver meaningful results from these alternative approaches with their resources.
- In ASPEN-03 and ASPEN-04 trials, efficacy data do not support advancing evorpacept in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), into a registrational study
- Company remains confident in continuing to pursue evorpacept in multiple clinical trials, based on the different mechanism of evorpacept in combination with anti-cancer antibodies, as evidenced by durable clinical response and consistent safety data in prior clinical trials
SOUTH SAN FRANCISCO, April 25, 2025 (GLOBE NEWSWIRE) -- ALX Oncology Holdings Inc., (“ALX Oncology” or the “Company”) (Nasdaq: ALXO), a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives, today announced topline data from its Phase 2 ASPEN-03 and ASPEN-04 clinical trials. The company’s investigational CD47-blocker evorpacept, when added to Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) with or without chemotherapy, did not meet the primary endpoints in the ASPEN-03 and ASPEN-04 trials of improved objective response rates (ORR) as compared to historical controls of pembrolizumab alone and pembrolizumab with chemotherapy, respectively, as a first-line treatment in patients with advanced head and neck squamous cell carcinoma (HNSCC). The combination of evorpacept and pembrolizumab with or without chemotherapy in ASPEN-03 and ASPEN-04 demonstrated a manageable safety profile and was consistent with what has been previously reported for pembrolizumab and chemotherapy in this setting. Although the company will no longer pursue evorpacept in combination with pembrolizumab in HNSCC, multiple clinical trials of evorpacept in combination with anti-cancer antibodies will continue based on established proof-of-concept.
Evorpacept blocks the ‘don’t eat me’ signal transmitted by CD47 on the surface of cancer cells that these cells use to evade detection by the immune system. As its primary mechanism of action, evorpacept is uniquely designed to stimulate macrophages to selectively attack cancer cells and not healthy cells, when combined with active anti-cancer antibodies. This mechanism has translated into durable clinical responses and a well-tolerated safety profile in HER2-positive gastric and HER2-positive breast cancer clinical trials. To further explore the benefit in this setting, evorpacept is currently being evaluated in combination with various anti-cancer antibodies in colorectal cancer, breast cancer, non-Hodgkin lymphoma and multiple myeloma.
In the ASPEN-03 and ASPEN-04 clinical trials, evorpacept was combined with pembrolizumab with or without chemotherapy to investigate a second and distinct mechanism of action. This discrete approach explored the concept that evorpacept may enhance T-cell priming by activating dendritic cells and stimulating the adaptive immune system. The trial outcomes were not sufficiently supportive of advancing evorpacept in combination with pembrolizumab in HNSCC into a registrational trial.
“While there were encouraging trends in ASPEN-03 in ORR versus the historical and internal control, we've decided not to pursue evorpacept and pembrolizumab in head and neck cancer in light of our prioritization of the more established anti-cancer antibody combination program based on multiple positive studies,” said Alan Sandler, M.D., Chief Medical Officer at ALX Oncology. “We are disappointed that these studies did not meet their primary endpoints, most importantly for the patients for whom current standard-of-care treatment approaches fall short, and we thank all who participated in the trials.”
“Moving forward, we are continuing to rapidly advance our clinical program combining evorpacept with anti-cancer antibodies supported by robust clinical data across trials in multiple tumor types. Evorpacept has demonstrated response rates and durability beyond what is expected from standard of care across several studies when combined with HERCEPTIN®, zanidatamab and RITUXAN®,” said Jason Lettmann, Chief Executive Officer at ALX Oncology. “Based on the positive data and strong mechanistic rationale, we maintain our confidence in the evorpacept clinical development program and intend to deliver on that promise with additional clinical data in breast cancer and colorectal cancer in the near-term. With evorpacept and ALX2004, our novel EGFR-targeted antibody-drug conjugate, we continue our commitment to bringing forth meaningful therapies for patients living with cancer.”
Detailed findings from the ASPEN-03 and ASPEN-04 trials will be submitted to a future medical meeting.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
About ASPEN-03 and ASPEN-04 Clinical Trials
ASPEN-03 and ASPEN-04 are randomized, multi-center, international Phase 2 trials evaluating evorpacept, ALX Oncology’s investigational CD47-blocking therapeutic that uniquely combines a high-affinity CD47-binding domain with an inactivated proprietary Fc domain, in patients with metastatic or unresectable, recurrent HNSCC who have not yet been treated for their advanced disease. The ASPEN-03 trial (NCT04675294) is evaluating evorpacept in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab) against pembrolizumab alone for the treatment of patients whose HNSCC is PD-L1 positive. The ASPEN-04 trial (NCT04675333) is evaluating evorpacept in combination with pembrolizumab and chemotherapy against pembrolizumab and chemotherapy alone in patients with HNSCC, regardless of PD-L1 status. Patient characteristics in the trials (N=346) were generally well-balanced across arms. The primary endpoints for the ASPEN-03 and ASPEN-04 trials is ORR compared to historical control. Key secondary endpoints for both trials are safety, duration of response (DOR), progression-free survival (PFS) and overall survival (OS).
About Head and Neck Squamous Cell Carcinoma (HNSCC)
HNSCC is a serious and life-threatening disease that originates in the squamous cells lining the mucosal surfaces of the head and neck, including the mouth, throat, voice box, sinuses and nasal cavity. HNSCC is the seventh most common cancer worldwide and the incidence of HNSCC is expected to increase
About Evorpacept
ALX Oncology's lead therapeutic candidate, evorpacept, is a highly differentiated potential best- and first-in-class CD47 checkpoint inhibitor and one of the most advanced checkpoint inhibitors to target and activate the innate immune system. Evorpacept was intentionally designed to maximize the clinical potential of blocking CD47, while reducing the toxicities associated with previous approaches to CD47 blockade. In clinical studies across a wide spectrum of tumor types in more than 700 patients to date, evorpacept has demonstrated potential to enhance the therapeutic activity of many of the most important cancer therapies available today, contributing an additional, differentiated immuno-oncology mechanism. Based on this potential, ALX Oncology is advancing a robust clinical program evaluating evorpacept in a wide range of cancer indications, prioritizing its combination with anti-cancer antibodies in breast, gastric and colon cancers. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to evorpacept for the second-line treatment of patients with HER2-positive gastric or GEJ carcinoma. Additionally, both the FDA and European Commission have granted Orphan Drug Designation for this indication.
About ALX Oncology
ALX Oncology (Nasdaq: ALXO) is a clinical-stage biotechnology company advancing a pipeline of novel therapies designed to treat cancer and extend patients’ lives. ALX Oncology’s lead therapeutic candidate, evorpacept, has demonstrated potential to serve as a cornerstone therapy upon which the future of immuno-oncology can be built. Evorpacept is currently being evaluated across multiple ongoing clinical trials in a wide range of cancer indications. ALX Oncology’s second pipeline candidate, ALX2004, is a novel EGFR-targeted antibody-drug conjugate with a differentiated mechanism of action and is anticipated to enter Phase 1 trials mid-2025. More information is available at www.alxoncology.com and on LinkedIn @ALX Oncology.
Cautionary note regarding forward-looking statements
This press release contains forward-looking statements that involve substantial risks and uncertainties. Forward-looking statements include statements regarding future results of operations and financial position, business strategy, product candidates, planned preclinical studies and clinical trials, results of clinical trials, research and development costs, regulatory approvals, timing and likelihood of success, plans and objects of management for future operations, as well as statements regarding industry trends. Such forward-looking statements are based on ALX Oncology’s beliefs and assumptions and on information currently available to it on the date of this press release. Forward-looking statements may involve known and unknown risks, uncertainties and other factors that may cause ALX Oncology’s actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. These and other risks are described more fully in ALX Oncology’s filings with the Securities and Exchange Commission (SEC), including ALX Oncology’s Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and other documents ALX Oncology files with the SEC from time to time. Except to the extent required by law, ALX Oncology undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Investor Relations Contact:
Elhan Webb, CFA, IR Consultant
ewebb@alxoncology.com
Media Contact:
Audra Friis, Sam Brown, Inc.
audrafriis@sambrown.com
(917) 519-9577
FAQ
What were the primary endpoints of ALXO's ASPEN-03 and ASPEN-04 trials?
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