ALX Oncology Announces First Patients Dosed with Evorpacept and Sarclisa As Part of Randomized Phase 1/2 UMBRELLA Study with Sanofi
ALX Oncology (Nasdaq: ALXO) has announced the dosing of first patients in a randomized Phase 1/2 UMBRELLA study, evaluating evorpacept in combination with Sanofi's SARCLISA® (isatuximab-irfc) for relapsed or refractory multiple myeloma (RRMM). Evorpacept is ALX Oncology's investigational CD47-blocking therapeutic, while SARCLISA is Sanofi's approved CD38 monoclonal antibody.
The study aims to assess the safety, efficacy, pharmacokinetics, and biomarker data of this combination. Part 1 will evaluate dosing, while Part 2 will investigate efficacy and safety in an expanded RRMM patient population. This collaboration leverages the potential synergy between evorpacept and SARCLISA, as CD47 expression increases with multiple myeloma progression, potentially re-sensitizing tumors to CD38 treatment.
ALX Oncology (Nasdaq: ALXO) ha annunciato la somministrazione ai primi pazienti in uno studio randomizzato di Fase 1/2 chiamato UMBRELLA, che valuta evorpacept in combinazione con il SARCLISA® di Sanofi (isatuximab-irfc) per il mieloma multiplo recidivato o refrattario (RRMM). Evorpacept è la terapia sperimentale di ALX Oncology che blocca il CD47, mentre SARCLISA è l'anticorpo monoclonale CD38 approvato da Sanofi.
Lo studio mira a valutare la sicurezza, l'efficacia, la farmacocinetica e i dati sui biomarcatori di questa combinazione. La Parte 1 valuterà il dosaggio, mentre la Parte 2 indagherà l'efficacia e la sicurezza in una popolazione ampliata di pazienti con RRMM. Questa collaborazione sfrutta la potenziale sinergia tra evorpacept e SARCLISA, poiché l'espressione del CD47 aumenta con la progressione del mieloma multiplo, potenzialmente ri-sensibilizzando i tumori al trattamento con CD38.
ALX Oncology (Nasdaq: ALXO) ha anunciado la dosificación de los primeros pacientes en un estudio aleatorizado de Fase 1/2 llamado UMBRELLA, que evalúa evorpacept en combinación con el SARCLISA® de Sanofi (isatuximab-irfc) para el mieloma múltiple recaído o refractario (RRMM). Evorpacept es el terapéutico en investigación de ALX Oncology que bloquea CD47, mientras que SARCLISA es el anticuerpo monoclonal CD38 aprobado por Sanofi.
El estudio tiene como objetivo evaluar la seguridad, eficacia, farmacocinética y datos de biomarcadores de esta combinación. La Parte 1 evaluará la dosificación, mientras que la Parte 2 investigará la eficacia y seguridad en una población ampliada de pacientes con RRMM. Esta colaboración aprovecha la sinergia potencial entre evorpacept y SARCLISA, ya que la expresión de CD47 aumenta con la progresión del mieloma múltiple, lo que puede re-sensibilizar a los tumores al tratamiento con CD38.
ALX Oncology(Nasdaq: ALXO)가 evorpacept와 Sanofi의 SARCLISA®(isatuximab-irfc)의 조합을 평가하는 무작위화된 1/2상 UMBRELLA 연구에서 첫 환자에 대한 투여를 발표했습니다. 재발성 또는 내성 다발성 골수종(RRMM)을 위한 것입니다. Evorpacept는 ALX Oncology의 CD47 차단 치료제이며, SARCLISA는 Sanofi의 승인된 CD38 단클론 항체입니다.
이 연구는 이 조합의 안전성, 효능, 약동학 및 바이오마커 데이터를 평가하는 것을 목표로 합니다. 1부는 용량을 평가하고, 2부는 확장된 RRMM 환자 집단에서 효능과 안전성을 조사할 것입니다. 이 협력은 evorpacept와 SARCLISA 간의 잠재적 시너지를 활용하며, CD47의 발현은 다발성 골수종의 진행 상황에 따라 증가하여 CD38 치료에 대해 종양을 재감작할 가능성이 있습니다.
ALX Oncology (Nasdaq: ALXO) a annoncé le traitement des premiers patients dans une étude randomisée de phase 1/2 appelée UMBRELLA, évaluant evorpacept en combinaison avec le SARCLISA® de Sanofi (isatuximab-irfc) pour le myélome multiple récurrent ou réfractaire (RRMM). Evorpacept est le traitement expérimental bloquant le CD47 d'ALX Oncology, tandis que SARCLISA est l'anticorps monoclonal CD38 approuvé par Sanofi.
L'étude vise à évaluer la safety, efficacy, pharmacokinetics, and biomarker data de cette combinaison. La partie 1 évaluera la dosage, tandis que la partie 2 étudiera l'efficacité et la sécurité dans une population élargie de patients atteints de RRMM. Cette collaboration exploite la synergie potentielle entre evorpacept et SARCLISA, l'expression de CD47 augmentant avec la progression du myélome multiple, ce qui pourrait potentiellement re-sensibiliser les tumeurs au traitement par CD38.
ALX Oncology (Nasdaq: ALXO) hat die Dosierung der ersten Patienten in einer randomisierten Phase 1/2 UMBRELLA-Studie angekündigt, die evorpacept in Kombination mit Sanofis SARCLISA® (isatuximab-irfc) zur Behandlung von rezidiviertem oder refraktärem multiplem Myelom (RRMM) evaluiert. Evorpacept ist die experimentelle CD47-blockierende Therapie von ALX Oncology, während SARCLISA der genehmigte CD38-Monoklonale Antikörper von Sanofi ist.
Die Studie zielt darauf ab, die Sicherheit, Wirksamkeit, Pharmakokinetik und Biomarker-Daten dieser Kombination zu bewerten. Teil 1 bewertet die Dosierung, während Teil 2 die Wirksamkeit und Sicherheit in einer erweiterten RRMM-Patientenpopulation untersuchen wird. Diese Zusammenarbeit nutzt die potenzielle Synergie zwischen evorpacept und SARCLISA, da die CD47-Expression mit dem Fortschreiten des multiplen Myeloms zunimmt und möglicherweise Tumoren wieder für die CD38-Behandlung sensibilisieren kann.
- Collaboration with Sanofi, a major pharmaceutical company, for the UMBRELLA study
- Potential for evorpacept to re-sensitize tumors to CD38 treatment or overcome anti-CD38 resistance
- Preclinical models demonstrated synergistic anti-tumor activity of the combination therapy
- ALX Oncology retains worldwide commercial rights to evorpacept
- Multiple myeloma remains an incurable hematologic malignancy
- The study is still in early phases (Phase 1/2), with efficacy and safety yet to be fully determined
Insights
This clinical study marks a significant milestone in the development of novel combination therapies for multiple myeloma. The pairing of ALX Oncology's evorpacept with Sanofi's SARCLISA targets two important pathways: CD47 and CD38. This approach could potentially overcome resistance to CD38-targeted therapies, a common challenge in relapsed/refractory multiple myeloma (RRMM).
The synergistic anti-tumor activity observed in preclinical models is promising. If successful, this combination could offer a new treatment option for RRMM patients who have exhausted other therapies. The study's design, including dose-finding and efficacy evaluation phases, is robust and well-structured to generate comprehensive data.
Investors should note that positive results could significantly impact ALX Oncology's market position and potentially lead to expanded applications for evorpacept in other hematological malignancies.
The initiation of this trial is a noteworthy development in multiple myeloma treatment. The combination of evorpacept and SARCLISA targets two distinct pathways critical in myeloma cell survival: CD47 and CD38. This dual-targeting approach could potentially enhance the depth and duration of response in RRMM patients.
Of particular interest is the potential to re-sensitize tumors to CD38 treatment or overcome anti-CD38 resistance. This could be a game-changer for patients who have progressed on current CD38-targeted therapies. The safety profile of evorpacept will be important to monitor, as combination therapies often carry increased toxicity risks.
If successful, this study could lead to a paradigm shift in how we approach refractory multiple myeloma, potentially improving outcomes in this difficult-to-treat patient population.
This clinical trial initiation is a positive development for ALX Oncology. The collaboration with Sanofi, a major player in oncology, lends credibility to evorpacept's potential and could lead to future partnership opportunities. The multiple myeloma market is substantial, with global sales projected to reach
Investors should note that ALX Oncology retains worldwide commercial rights to evorpacept, which could translate to significant revenue if the drug is successful. However, it's important to remember that clinical trials, especially in early phases, carry inherent risks.
The company's stock may see increased volatility as trial results are announced. Positive data could drive substantial upside, while negative results could significantly impact the stock price. Long-term investors should monitor the trial's progress closely as it could be a major value driver for ALX Oncology.
Clinical study is evaluating ALX Oncology’s investigational CD47-blocking therapeutic with Sanofi’s approved CD38 monoclonal antibody in patients with multiple myeloma
SOUTH SAN FRANCISCO, Calif., Sept. 04, 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, announced the first patients have been dosed in an arm of the randomized UMBRELLA phase 1/2 clinical study partnered with Sanofi that is evaluating evorpacept in combination with SARCLISA® (isatuximab-irfc). Evorpacept is ALX Oncology’s investigational CD47-blocking therapeutic that uniquely combines a high-affinity CD47-binding domain with an inactivated Fc domain and SARCLISA is Sanofi’s approved CD38 monoclonal antibody in patients with relapsed or refractory multiple myeloma (RRMM).
SARCLISA binds to a specific epitope on the CD38 receptor on multiple myeloma (MM) cells, inducing distinct antitumor activity. CD38 is highly and uniformly expressed on the surface of MM cells and after first-line treatment, some relapsed or recurred patients have shown resistance to CD38 agents. CD47 expression increases as multiple myeloma progresses, suggesting that evorpacept may have the potential to re-sensitize tumors to CD38 treatment or overcome anti-CD38 resistance. This novel therapeutic combination has demonstrated synergistic anti-tumor activity in preclinical models.
“Multiple myeloma remains an incurable hematologic malignancy for which there is significant need for innovation in new treatment modalities to improve the clinical management of this disease,” said Sophia Randolph, M.D., Ph.D., Chief Medical Officer at ALX Oncology. “We are excited by the potential for the therapeutic combination being evaluated in the UMBRELLA study, in collaboration with Sanofi, to improve patient outcomes. This trial also reinforces the significant potential of evorpacept to deepen anti-cancer activity while maintaining a strong safety profile in combination with a range of therapeutic regimens used to treat both hematologic and solid cancers.”
Under the terms of the agreement, Sanofi will conduct the multicenter, randomized, open-label, controlled, parallel-group UMBRELLA phase 1/2 clinical study (NCT04643002) to evaluate the safety, efficacy, pharmacokinetics and biomarker data of evorpacept in combination with SARCLISA and dexamethasone in patients with RRMM. Part 1 of the study is designed to evaluate the dosing of evorpacept in combination with standard doses of SARCLISA and dexamethasone to identify a recommended evorpacept dose. Part 2 is designed to investigate the efficacy and safety of this three-drug combination in an expanded population of patients with RRMM. ALX Oncology will supply evorpacept and Sanofi will conduct the clinical trial. ALX Oncology owns worldwide commercial rights to evorpacept.
“Our current experience with SARCLISA suggests it may prove to be an excellent combination partner for novel agents in development,” said Peter C. Adamson, M.D., Global Head of Oncology Development at Sanofi. “Therefore, we are pleased to share we have started to enroll patients on this arm of our umbrella study. The partnership with ALX Oncology is part of our strategic approach of exploring potentially synergistic combinations to address therapeutic challenges in patients with relapsed or refractory multiple myeloma.”
About multiple myeloma
Multiple myeloma (MM) is the second most common hematologic malignancy, with more than 185,000 new diagnoses of MM worldwide annually (Globocan) and over 35,000 new diagnoses in the United States each year (American Cancer Society). Despite available treatments, MM remains an incurable malignancy and is associated with significant patient burden. Since MM does not have a cure, most patients will relapse. Relapsed MM is the term for when the cancer returns after treatment or a period of remission. Refractory MM refers to when the cancer does not respond or no longer responds to therapy.
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 (ADCs), 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.
About SARCLISA
SARCLISA (isatuximab-irfc) is a monoclonal antibody that binds to a specific epitope on the CD38 receptor on MM cells, inducing distinct antitumor activity. It is designed to work through multiple mechanisms of action including programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on the surface of MM cells, making it a target for antibody-based therapeutics such as SARCLISA. SARCLISA is approved in more than 50 countries, including the US and the EU, in combination with pomalidomide and dexamethasone for the treatment of patients with RRMM who have received ≥2 prior therapies, including lenalidomide and a proteasome inhibitor and who progressed on last therapy. SARCLISA is also approved in 50 countries in combination with carfilzomib and dexamethasone, including in the US for the treatment of patients with RRMM who have received 1–3 prior lines of therapy and in the EU for patients with MM who have received at least one prior therapy. SARCLISA continues to be evaluated in multiple ongoing phase 3 clinical studies in combination with current standard treatments across the MM treatment continuum. It is also under investigation for the treatment of other hematologic malignancies, and its safety and efficacy have not been evaluated by any regulatory authority outside of its approved indication.
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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