ALX Oncology Reports Topline Data From ASPEN-06 Phase 2 Trial Demonstrating Evorpacept Improves Tumor Response in Patients With HER2-Positive Gastric Cancer
ALX Oncology (Nasdaq: ALXO) announced topline data from its Phase 2 ASPEN-06 clinical trial, evaluating evorpacept in combination with trastuzumab, ramucirumab, and paclitaxel (TRP) for HER2-positive gastric or gastroesophageal junction cancer. Key findings include:
1. In the full population (N=127), evorpacept + TRP showed an overall response rate (ORR) of 40.3% vs 26.6% for TRP alone.
2. In patients with fresh HER2-positive biopsies (n=48), evorpacept + TRP achieved an ORR of 54.8% vs 23.1% for TRP alone.
3. Median duration of response was 15.7 months for evorpacept + TRP vs 7.6 months for TRP alone.
4. Evorpacept + TRP was generally well-tolerated.
These results mark evorpacept as the first CD47 blocker to show durable clinical benefit in a randomized trial, supporting its development in combination with anti-cancer antibodies for various tumor types.
ALX Oncology (Nasdaq: ALXO) ha annunciato i dati preliminari del suo trial clinico di fase 2 ASPEN-06, che valuta evorpacept in combinazione con trastuzumab, ramucirumab e paclitaxel (TRP) per il cancro gastrico HER2-positivo o del giunzione gastroesofagea. I principali risultati includono:
1. Nella popolazione complessiva (N=127), evorpacept + TRP ha mostrato un tasso di risposta globale (ORR) del 40,3% rispetto al 26,6% per TRP da solo.
2. Nei pazienti con biopsie HER2-positive recenti (n=48), evorpacept + TRP ha raggiunto un ORR del 54,8% rispetto al 23,1% per TRP da solo.
3. La durata mediana della risposta è stata di 15,7 mesi per evorpacept + TRP contro 7,6 mesi per TRP da solo.
4. Evorpacept + TRP è stato generalmente ben tollerato.
Questi risultati segnano evorpacept come il primo bloccante CD47 a mostrare un beneficio clinico duraturo in un trial randomizzato, supportando il suo sviluppo in combinazione con anticorpi anti-cancro per vari tipi di tumori.
ALX Oncology (Nasdaq: ALXO) anunció los datos preliminares de su ensayo clínico de fase 2 ASPEN-06, que evalúa evorpacept en combinación con trastuzumab, ramucirumab y paclitaxel (TRP) para el cáncer gástrico HER2-positivo o de la unión gastroesofágica. Los hallazgos clave incluyen:
1. En la población total (N=127), evorpacept + TRP mostró una tasa de respuesta global (ORR) del 40.3% frente al 26.6% para TRP solo.
2. En pacientes con biopsias HER2-positivas recientes (n=48), evorpacept + TRP alcanzó un ORR del 54.8% frente al 23.1% para TRP solo.
3. La duración media de la respuesta fue de 15.7 meses para evorpacept + TRP frente a 7.6 meses para TRP solo.
4. Evorpacept + TRP fue generalmente bien tolerado.
Estos resultados marcan a evorpacept como el primer bloqueador de CD47 que muestra un beneficio clínico duradero en un ensayo aleatorio, apoyando su desarrollo en combinación con anticuerpos anticancerígenos para varios tipos de tumores.
ALX Oncology (Nasdaq: ALXO)는 HER2 양성 위암 또는 위식도 접합부 암에 대한 evorpacept와 trastuzumab, ramucirumab, paclitaxel (TRP)의 병용 요법을 평가하는 2상 ASPEN-06 임상 시험의 최종 데이터를 발표했습니다. 주요 발견은 다음과 같습니다:
1. 전체 모집단(N=127)에서 evorpacept + TRP는 총 반응률(ORR) 40.3%를 기록했으며, TRP 단독의 경우 26.6%였습니다.
2. 최근 HER2 양성 생검을 받은 환자(n=48)에서 evorpacept + TRP는 ORR 54.8%를 달성했으며, TRP 단독의 경우 23.1%였습니다.
3. 반응의 중앙 지속 기간은 evorpacept + TRP에서 15.7개월, TRP 단독에서 7.6개월이었습니다.
4. Evorpacept + TRP는 일반적으로 잘 견디는 것으로 나타났습니다.
이 결과는 evorpacept가 무작위 시험에서 지속적인 임상적 이점을 보인 첫 번째 CD47 차단제라는 점을 의미하며, 다양한 종양 유형에 대한 항암 항체와의 조합 개발을 뒷받침하고 있습니다.
ALX Oncology (Nasdaq: ALXO) a annoncé les données principales de son essai clinique de phase 2 ASPEN-06, évaluant evorpacept en combinaison avec trastuzumab, ramucirumab et paclitaxel (TRP) pour le cancer gastrique HER2-positif ou du junction gastro-œsophagien. Les résultats clés incluent :
1. Dans la population totale (N=127), evorpacept + TRP a montré un taux de réponse global (ORR) de 40,3% contre 26,6% pour TRP seul.
2. Chez les patients ayant récemment subi une biopsie HER2-positive (n=48), evorpacept + TRP a atteint un ORR de 54,8% contre 23,1% pour TRP seul.
3. La durée médiane de la réponse était de 15,7 mois pour evorpacept + TRP contre 7,6 mois pour TRP seul.
4. Evorpacept + TRP a été généralement bien toléré.
Ces résultats marquent evorpacept comme le premier bloqueur CD47 à montrer un bénéfice clinique durable dans un essai randomisé, soutenant son développement en combinaison avec des anticorps anti-cancer pour divers types de tumeurs.
ALX Oncology (Nasdaq: ALXO) hat die Zwischenergebnisse seiner Phase-2-Studie ASPEN-06 veröffentlicht, die evorpacept in Kombination mit Trastuzumab, Ramucirumab und Paclitaxel (TRP) bei HER2-positivem Magen- oder gastroösophagealen Übergangskarzinom untersucht. Die wichtigsten Ergebnisse umfassen:
1. In der Gesamtpopulation (N=127) zeigte evorpacept + TRP eine Gesamtansprechrate (ORR) von 40,3% im Vergleich zu 26,6% bei TRP allein.
2. Bei Patienten mit neuen HER2-positiven Biopsien (n=48) erreichte evorpacept + TRP eine ORR von 54,8% im Vergleich zu 23,1% bei TRP allein.
3. Die mittlere Dauer der Antwort betrug 15,7 Monate für evorpacept + TRP im Vergleich zu 7,6 Monaten für TRP allein.
4. Evorpacept + TRP wurde im Allgemeinen gut vertragen.
Diese Ergebnisse zeigen, dass evorpacept der erste CD47-Blocker ist, der in einer randomisierten Studie einen nachhaltigen klinischen Nutzen zeigt und seine Entwicklung in Kombination mit anti-Krebs-Antikörpern für verschiedene Tumorarten unterstützt.
- Evorpacept + TRP achieved a higher overall response rate (40.3%) compared to TRP alone (26.6%) in the full trial population
- In patients with fresh HER2-positive biopsies, evorpacept + TRP showed a significantly higher ORR (54.8%) vs TRP alone (23.1%)
- Median duration of response was more than doubled with evorpacept + TRP (15.7 months) compared to TRP alone (7.6 months)
- Evorpacept is the first CD47 blocker to demonstrate clinical benefit in a randomized trial
- The combination of evorpacept with TRP was generally well-tolerated
- FDA granted Fast Track designation for evorpacept in second-line treatment of HER2-positive gastric or GEJ carcinoma
- FDA and European Commission granted Orphan Drug Designation for evorpacept in this indication
- Secondary endpoints of progression-free survival (PFS) and overall survival (OS) were immature at the time of analysis
Insights
The topline data from ALX Oncology's ASPEN-06 Phase 2 trial for evorpacept in HER2-positive gastric cancer is highly significant. Here's why:
- Evorpacept, combined with standard therapy, showed a substantial improvement in overall response rate (ORR):
40.3% vs26.6% in the control arm. This13.7% difference exceeds the pre-specified threshold of10% , indicating clinical relevance. - The median duration of response (mDOR) more than doubled: 15.7 months for evorpacept vs 7.6 months for control. This suggests evorpacept may offer more durable benefits.
- In patients with fresh HER2-positive biopsies, the effect was even more pronounced: ORR of
54.8% vs23.1% . This correlation between HER2 expression and efficacy validates evorpacept's mechanism of action.
These results are particularly impressive given that all patients had previously received anti-HER2 therapy. It suggests evorpacept could offer a valuable option for patients who've progressed on current treatments. However, we should note that progression-free survival (PFS) and overall survival (OS) data are still immature, which will be important for fully understanding the drug's impact.
The safety profile appears favorable, which is critical for a combination therapy in this setting. As the first CD47 blocker to show durable clinical benefit in a randomized trial, evorpacept represents a potential breakthrough in immuno-oncology for gastric cancer.
This data release significantly bolsters ALX Oncology's position in the competitive immuno-oncology landscape. Key investment considerations include:
- Market potential: Gastric cancer is the 5th most common cancer globally, with HER2-positive cases representing about
20% of patients. Evorpacept's efficacy in this population, especially after progression on existing HER2-targeted therapies, suggests a substantial market opportunity. - Competitive advantage: As the first CD47 blocker to demonstrate clinical benefit in a randomized trial, ALX Oncology may have a first-mover advantage in this novel approach to immuno-oncology.
- Regulatory tailwinds: The FDA's Fast Track designation and Orphan Drug Designation from both FDA and European Commission could accelerate evorpacept's path to market and provide extended market exclusivity.
- Pipeline potential: The positive results in gastric cancer support exploring evorpacept's potential in other tumor types, potentially expanding ALX's pipeline and market opportunities.
However, investors should note that PFS and OS data are still pending, which will be important for determining evorpacept's full clinical and commercial potential. Additionally, while the safety profile appears favorable, more detailed safety data will be important for assessing the risk-benefit ratio.
Financially, these results likely strengthen ALX Oncology's position for potential partnerships or funding rounds. The company's ability to advance evorpacept through later-stage trials and potentially to market will be critical for long-term value creation.
- Evorpacept is the first CD47 blocker to show durable clinical benefit and a well-tolerated safety profile in a prospective randomized trial
- Evorpacept combination achieved a confirmed overall response rate (ORR) of
40.3% compared to26.6% for the control arm and demonstrated a median duration of response of 15.7 months compared to 7.6 months in the full trial population - In the pre-specified population of patients with fresh HER2-positive biopsies, evorpacept combination showed the greatest benefit with ORR of
54.8% vs.23.1% in the control, suggesting HER2-expression strongly correlates with evorpacept efficacy and validating its mechanism of action - Company to host conference call and webcast today at 4:30 PM EDT
SOUTH SAN FRANCISCO, Calif., July 31, 2024 (GLOBE NEWSWIRE) -- ALX Oncology Holdings Inc., (“ALX Oncology” or the “Company”) (Nasdaq: ALXO), an immuno-oncology company developing therapies that block the CD47 immune checkpoint pathway, today announced topline data from its Phase 2 ASPEN-06 clinical trial. The trial demonstrated clinically meaningful improvements in overall response rate and duration of response among patients with previously treated HER2-positive advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer.
“The topline results from the ASPEN-06 clinical trial confirm the robust response that evorpacept can deliver, generating a clinically meaningful impact on key measures of anti-cancer activity for patients with gastric cancers and continuing to surpass benchmarks in the field,” said Jason Lettmann, chief executive officer at ALX Oncology. “Additionally, they provide valuable insight beyond the interim data previously reported, offering a more conclusive look at the impact of evorpacept and identifying the most responsive patient population. Importantly, the level of clinical benefit seen in this trial provides support for developing evorpacept in combination with anti-cancer antibodies in additional tumor types and drives ALX’s development strategy.”
ASPEN-06 is a randomized, multi-center, international trial 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 combination with trastuzumab, CYRAMZA® (ramucirumab) and paclitaxel (collectively, TRP) against TRP alone for the treatment of patients with HER2-positive gastric/GEJ cancer, where all patients had received an anti-HER2 agent in prior lines of therapy. Patients in the trial (N=127) were generally well-balanced across arms based on pre-specified stratification factors including line of therapy, prior ENHERTU® (fam-trastuzumab deruxtecan-nxki) use, Asia region, tumor location (GC or GEJ), HER2 expression level (IHC3+ or IHC2+/ISH+) and HER2-positive biopsy (fresh or archival).
The trial’s primary endpoint is overall response rate (ORR). Key secondary endpoints are safety, median duration of response (mDOR), progression-free survival (PFS) and overall survival (OS).
Key Phase 2 ASPEN-06 Clinical Trial Topline Results:
- In the full intent-to-treat population (N=127), the addition of evorpacept to TRP demonstrated an ORR of
40.3% compared to the TRP control ORR of26.6% - In patients with fresh HER2-positive biopsies (n=48), evorpacept plus TRP demonstrated an ORR of
54.8% compared to23.1% for the TRP control - Median duration of response (DOR) in the evorpacept arm was 15.7 months [
95% CI: 11.0; NE] compared to the TRP control of 7.6 months [95% CI: 6.3; NE] in the full intent-to-treat population - Secondary endpoints of PFS and OS were immature at the time of analysis
- Evorpacept in combination with TRP was generally well tolerated and consistent with TRP control
“By meeting our clinically meaningful and pre-specified threshold of greater than
The ASPEN-06 full data set will be submitted for presentation at an upcoming medical conference.
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.
Conference Call and Webcast on July 31 at 4:30 PM EDT
The Company will host a conference call and webcast today at 4:30 PM EDT. To access the live conference call, please dial (800) 715-9871 (U.S./Canada) or +44.800.260.6466 (internationally) at least 10 minutes prior to the start time and refer to conference ID 9637001. The link to the live webcast of the conference call will be posted in the News & Events section (see “Events”) of the Company’s website at www.alxoncology.com. An archived replay will be accessible for 90 days following the event.
About the ASPEN-06 Phase 2 Clinical Trial
ASPEN-06 is a randomized Phase 2 (open-label) / Phase 3 (double-blinded), multi-center, international trial of patients with second- or third-line metastatic HER2-overexpressing gastric/GEJ adenocarcinoma that progressed on or after prior HER2-directed therapy and fluoropyrimidine- or platinum-containing chemotherapy (NCT05002127). HER2 status was determined by an FDA-approved test in the most recent gastric/GEJ cancer tissue sample. The primary analysis of the full intent-to-treat population included all randomized patients whose HER2 status was based on a tissue sample obtained at any time. An additional primary analysis was conducted on patients who had a recent HER2-positive tissue sample after prior anti-HER2 therapy (“fresh biopsy”). While trastuzumab is currently approved in combination with cisplatin and capecitabine/5-FU for HER2-positive gastric/GEJ cancers, it is not approved in combination with standard-of-care CYRAMZA + paclitaxel. The Phase 2 portion of the ASPEN-06 trial enrolled 127 patients. To determine the activity of evorpacept + trastuzumab + CYRAMZA + paclitaxel, in the Phase 2 portion of ASPEN-06, patients were randomized to receive either a four-drug combination regimen (evorpacept + trastuzumab + CYRAMZA + paclitaxel) or a three-drug combination regimen (trastuzumab + CYRAMZA + paclitaxel). This design enabled the assessment of evorpacept’s contribution to the standard of care plus trastuzumab and to global standard of care, CYRAMZA + paclitaxel.
About ALX Oncology
ALX Oncology is a publicly traded, clinical-stage immuno-oncology company focused on helping patients fight cancer by developing therapies that block the CD47 immune checkpoint inhibitor and bridge the innate and adaptive immune system. ALX Oncology’s lead product candidate, evorpacept, is a CD47 blocking therapeutic that combines a high-affinity CD47-binding domain with an inactivated, proprietary Fc domain. To date, evorpacept has been dosed in over 500 subjects and has demonstrated promising activity and favorable tolerability profile across a range of hematologic and solid malignancies in combination with various leading anti-cancer antibodies. ALX Oncology is currently focusing on combining evorpacept with anti-cancer antibodies, antibody-drug conjugates and PD-1/PD-L1 immune checkpoint inhibitors.
Evorpacept’s Unique Profile: Anchored by a Rational Design and Triple Development Pillars
Rationally engineered with an inactive Fc effector function, evorpacept’s clinical data to date have demonstrated a substantially improved safety profile over other anti-CD47 molecules in the clinic with an active Fc (i.e., binding the Fc gamma receptor on macrophages). This best-in-class safety profile allows for higher dosage with minimal overlapping toxicity in the combination treatment setting. CD47 expressed on cancer cells binds to its receptor SIRP alpha, which is predominantly expressed on two cell types: macrophages and dendritic cells. The Company’s pipeline of therapeutic candidates with standard-of-care agents include:
- Anti-cancer antibodies and ADCs (the “don’t eat me” signal): evorpacept enables Fc-mediated antibody-dependent phagocytosis by macrophages in combination with anti-cancer antibodies (e.g., Herceptin®) and ADCs (e.g., PADCEV and ENHERTU®) with an active Fc domain, which is otherwise impaired by CD47 expression on cancer cells binding to SIRP alpha on macrophages. Additionally, ADCs target the delivery of a chemotherapeutic payload to tumor cells to exert cytotoxic effects.
- PD-1/PD-L1 immune checkpoint inhibitors (the “don’t activate T-cells” signal): evorpacept enables T-cell activation by dendritic cells that are constitutively inhibited by CD47 expression on cancer cells binding to SIRP alpha on dendritic cells. Activated dendritic cells present neoantigens to T cells that once activated will kill cancer cells when the PD-1/PD-L1 inhibitory interaction is blocked by T-cell checkpoint inhibitors.
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.
FAQ
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