– 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%)
April 09, 2024 -- 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.”
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.
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.
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.
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.
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.
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