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ALX Oncology Reports Encouraging Clinical Data of Evorpacept in Combination with Standard-of-Care in an Ongoing Phase 1/2 Clinical Trial in Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (“R/R B-NHL”)

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ALX Oncology Reports Positive Clinical Data on Evorpacept in Combination with R2 for R/R B-NHL Patients
Positive
  • ALX Oncology reported encouraging clinical data from a Phase 1/2 trial of evorpacept in combination with R2 for indolent and aggressive R/R B-NHL patients.
  • The combination of evorpacept plus R2 showed promising initial activity with a 94% overall response rate and an 83% complete response rate in patients with indolent R/R B-NHL.
  • The safety profile of evorpacept plus R2 was similar to historical R2 data, with no dose-limiting toxicities reported.
  • Patients with indolent R/R B-NHL had significantly higher response rates compared to the benchmark study with R2 alone.
  • The data were presented at the 2024 AACR Annual Meeting, demonstrating the potential of evorpacept in combination therapies for B-NHL patients.
Negative
  • None.

The recent clinical trial outcomes for evorpacept, an immune checkpoint inhibitor targeting CD47, combined with R2 (rituximab and lenalidomide) in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (R/R B-NHL), are noteworthy for several reasons. Firstly, the observed complete response rate (CRR) of 83% in indolent R/R B-NHL patients represents a significant improvement over the historical benchmark CRR of 34% from the AUGMENT Phase 3 clinical trial. This suggests a potential paradigm shift in the treatment efficacy for this patient group.

From a medical research perspective, the safety profile of evorpacept in combination with R2 aligns with historical data, which is important in oncology treatments where the therapeutic window is often narrow. The absence of dose-limiting toxicities and treatment-related deaths provides a positive signal regarding the tolerability of the regimen. Moreover, the involvement of innate immune response as a mechanism of anti-tumor activity could indicate a broader applicability of evorpacept across various oncology indications, beyond B-NHL.

While these results are preliminary, they could lead to changes in clinical practice if substantiated by further trials. It is also important to note that the sample size is relatively small and the aggressive R/R B-NHL subgroup only included two patients, limiting the generalizability of the findings to this population.

As an oncologist, the clinical data presented for evorpacept in combination with R2 is encouraging, particularly because it addresses a patient population with limited treatment options after first-line therapy. The high best overall response rate (ORR) and CRR observed in the trial could translate to improved patient outcomes, including longer progression-free survival and potentially overall survival, though long-term data are needed to confirm this.

The management of adverse events is a critical aspect of cancer therapy. The most common side effects reported were fatigue and liver enzyme increases, which are manageable in a clinical setting. This favorable safety profile may improve patients' quality of life during treatment, which is a key consideration in chronic conditions such as indolent B-NHL.

It is also worth discussing the role of immunomodulatory drugs like lenalidomide in enhancing the efficacy of immunotherapies. The synergy between evorpacept and lenalidomide could represent an important avenue for future research, potentially leading to the development of more effective combination regimens.

From an investment standpoint, the promising results of ALX Oncology's evorpacept in combination with R2 could have significant implications for the company's financial health and market position. The superior efficacy data compared to the historical benchmark could position evorpacept as a competitive player in the B-NHL treatment landscape, potentially leading to increased market share and revenue for ALX Oncology.

Investors will likely monitor the ongoing Phase 2 trials closely, as further positive results could drive regulatory approval and commercialization prospects. Additionally, the drug's safety profile and efficacy in a niche yet significant market segment can attract partnership opportunities, boosting upfront payments and milestone revenues.

However, the market response will also depend on the drug's pricing strategy, reimbursement scenarios and the competitive landscape, including the entry of biosimilars and other novel therapies. Investors should consider these factors alongside the clinical data when evaluating the potential impact on ALX Oncology's stock performance.

– Twenty patients with indolent (n=18) and aggressive (n=2) R/R B-NHL received evorpacept plus standard rituximab and lenalidomide (“R2”)
– Evorpacept plus R2 was well tolerated with a safety profile similar to historical R2
– The combination achieved promising initial activity with a best overall response rate (“ORR”) of 94% and a complete response rate (“CRR”) of 83% in patients with indolent R/R B-NHL (R2 historical CRR benchmark is 34%)

SOUTH SAN FRANCISCO, Calif., April 09, 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 reported encouraging clinical data from the ongoing Phase 1/2 investigator-sponsored trial (“IST”) of evorpacept in combination with R2 in patients with indolent and aggressive R/R B-NHL. The new data were presented in an oral presentation at the 2024 American Association for Cancer Research (“AACR”) Annual Meeting.

The clinical trial enrolled a total of 20 patients with indolent (n=18) and aggressive (n=2) R/R B-NHL where all patients had received prior rituximab and 72% had received prior chemoimmunotherapy. Patients received evorpacept 30 mg/kg Q2W (n=3) or 60 mg/kg Q4W (n=17) in combination with standard R2 treatment. The regimen was well tolerated, and there were no dose-limiting toxicities. The maximum administered dose for evorpacept was 60 mg/kg Q4W. The most common adverse events due to any cause were fatigue, ALT increase, anemia, and AST increase, all of which were mostly low grade. There were no reported treatment-related deaths on study. Patients with indolent R/R B-NHL (n=18) had a best ORR of 94% and a CRR of 83%. The median duration of response was not reached. The AUGMENT Phase 3 clinical trial1, a benchmark study in a similar patient population, reported an ORR of 78% and a CRR of 34% with R2 alone.

“While standard frontline treatments have shown benefit in the indolent B-NHL setting, many patients are likely to see their disease progress after initial treatment,” said Paolo Strati, M.D., the trial’s lead investigator and Assistant Professor of Lymphoma-Myeloma at The University of Texas MD Anderson Cancer Center. “We are pleased evorpacept in combination with R2 demonstrated a favorable safety profile and encouraging response in this patient population. These data further illustrate the importance of exploring novel combinations with evorpacept to elicit anti-tumor activity by way of the innate immune response. We are excited to build upon these preliminary results as we evaluate the evorpacept-R2 combination in the ongoing Phase 2 portion of this clinical trial in patients with previously untreated indolent B-NHL.”

“These initial results reinforce evorpacept’s differentiated drug design that has resulted in anti-cancer activity while minimizing hematologic toxicities inherent to other CD47 blocking agents,” said Sophia Randolph, M.D., Ph.D., Chief Medical Officer, ALX Oncology. “Furthermore, the findings presented today build upon the promising data reported from the ASPEN-01 Phase 1 clinical trial of evorpacept in combination with rituximab in R/R NHL2. We look forward to applying these and other clinical trial data to inform new evorpacept combinations in our expanding pipeline. We would like to thank the patients and research team for conducting this important clinical trial.”

Details of the Oral Presentation at the 2024 AACR Annual Meeting are as follows:

A Phase 1 investigator-initiated trial of evorpacept (ALX148), lenalidomide and rituximab for patients with relapsed or refractory B-cell non-Hodgkin lymphoma
Session Title: Clinical Trials Minisymposium / Novel Agents and Emerging Therapeutic Strategies
Presentation Date and Time: Tuesday, April 9, 2024, 2:50 PM – 3:00 PM PT
Abstract: CT037 (full abstract is available online here)

The presentation is available on the publications page of the ALX Oncology website here.

About the Phase 1/2 IST Investigating Evorpacept Combination to Rin NHL

The Phase 1/2 IST is an ongoing, open-label, single arm clinical trial designed to evaluate the safety, tolerability, and efficacy of evorpacept, otherwise known as ALX148, in combination with R2 in patients with R/R B-cell NHL (both indolent and aggressive) histology. Patient enrollment is currently open to the Phase 2 portion of the study evaluating patients with previously untreated indolent B-NHL (NCT05025800). The study is sponsored and conducted by MD Anderson Cancer Center.

About Non-Hodgkin Lymphoma

Approximately 500,000 people worldwide are diagnosed with NHL each year. In the U.S., NHL is the seventh most common type of cancer, and over 80,000 newly cases of NHL were estimated in 20233. NHL can be divided into two groups according to how the disease progresses: indolent and aggressive lymphomas. The most prevalent form of NHL, accounting for about 32% of newly diagnosed NHL cases, is an aggressive form called diffuse large B-cell lymphoma. Follicular lymphoma is the most common subtype of indolent NHL and accounts for about 17% of newly diagnosed NHL cases. Indolent B-cell lymphomas tend to grow more slowly and may have fewer signs and symptoms than aggressive lymphomas when first diagnosed. For patients with indolent B-cell lymphoma, current first-line treatments include radiotherapy, anti-CD20 monoclonal antibodies, and chemoimmunotherapy. Despite advances in treatment, follicular lymphoma remains a significant cause of death.

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 next generation 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 Dual Development Pillars

Rationally engineered with an inactive Fc effector function, evorpacept’s clinical data to date has 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 (the “don’t eat me” signal): evorpacept enables Fc-mediated antibody-dependent phagocytosis by macrophages in combination with anti-cancer antibodies (e.g., Herceptin®) with an active Fc domain, which is otherwise impaired by CD47 expression on cancer cells binding to SIRP alpha on macrophages. This same mechanism of action applies to ADCs.
  • 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.

References

  • 1 Leonard J.P., et al. AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. doi: 10.1200/JCO.19.00010. Epub 2019 Mar 21. PMID: 30897038; PMCID: PMC7035866.
  • 2 Kim T., et al. ALX148, A CD47 Blocker, in Combination with Rituximab in Patients with R/R Non-Hodgkin Lymphoma. EHA Library. 06/12/2020 293736; EP1247.
  • 3 American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024.

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 and Media Contact:

Caitlyn Doherty
Manager, Investor Relations and Corporate Communications, ALX Oncology
cdoherty@alxoncology.com
(650) 466-7125


FAQ

What clinical data did ALX Oncology report regarding evorpacept in the PR?

ALX Oncology reported positive clinical data from a Phase 1/2 trial of evorpacept in combination with R2 for R/R B-NHL patients.

What were the overall response rate and complete response rate in patients with indolent R/R B-NHL?

The combination of evorpacept plus R2 showed a 94% overall response rate and an 83% complete response rate in patients with indolent R/R B-NHL.

What was the safety profile of evorpacept plus R2 compared to historical R2 data?

The safety profile of evorpacept plus R2 was similar to historical R2 data, with no dose-limiting toxicities reported.

How did patients with indolent R/R B-NHL respond to the evorpacept plus R2 combination?

Patients with indolent R/R B-NHL had significantly higher response rates with evorpacept plus R2 compared to the benchmark study with R2 alone.

Where were the new clinical data presented?

The new clinical data on evorpacept in combination with R2 were presented at the 2024 AACR Annual Meeting.

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About ALXO

alx oncology (previously alexo therapeutics) is a clinical-stage immuno-oncology company developing therapies that block the cd47 myeloid checkpoint mechanism exploited by cancer cells to evade the immune system. our lead candidate, alx148, is a fusion protein that comprises an engineered high affinity cd47 binding domain of sirpa linked to an inactive fc region of human immunoglobulin. alx148 is currently being investigated in a phase 1 study in combination with checkpoint inhibitors and targeted anti-cancer antibodies (nct03013218). for more information about the company, please visit our website at www.alxoncology.com