ALX Oncology Presents First Evorpacept Combination Data with an Antibody-Drug Conjugate from Phase 1 ASPEN-07 Clinical Trial in Patients with Advanced Bladder Cancer
ALX Oncology presented promising data from its Phase 1 ASPEN-07 clinical trial at the 2024 ASCO Annual Meeting. The trial investigated the combination of evorpacept and PADCEV in patients with advanced bladder cancer. Key results include a 59% overall response rate (ORR) as of April 3, 2024, with no maximum tolerated dose reached and no treatment-related deaths. Most adverse events were low-grade. Continued follow-up and new cohort enrollment are underway. ALX will host a virtual event on June 7, 2024, to discuss these findings.
- Promising 59% overall response rate (ORR) for evorpacept and PADCEV combination.
- No maximum tolerated dose reached, indicating good tolerance.
- No treatment-related deaths reported.
- 58% of patients remain in the study, showing ongoing engagement.
- Two confirmed complete responses and six confirmed partial responses.
- New cohort enrollment for patients who previously received PADCEV has begun.
- 93% of patients had metastatic disease, indicating a severely ill population.
- 29% of patients had received three or more prior lines of therapy, showing heavily pre-treated population.
- Common adverse events included fatigue, dysgeusia, nausea, diarrhea, hyperglycemia, and pruritis.
- Results remain unconfirmed and are from an early phase trial, requiring further validation.
Insights
The preliminary data from the ASPEN-07 clinical trial of evorpacept combined with PADCEV (enfortumab vedotin) has shown promise for patients with advanced bladder cancer, particularly those who have exhausted other treatment options. This combination therapy achieved an unconfirmed overall response rate (ORR) of 59% in a heavily pre-treated patient population, which is notably higher than the 41% ORR benchmark for PADCEV alone. Furthermore, no maximum tolerated dose has been reached and the therapy was generally well-tolerated, which is important for patients who have already undergone multiple lines of therapy.
From a clinical perspective, these early-stage results are encouraging. They suggest that the combination of a CD47 blocker with an antibody-drug conjugate (ADC) may provide a new therapeutic option for patients with limited alternatives. However, it's important to note that these are early findings from a Phase 1 trial. Long-term efficacy, overall survival benefits and quality of life improvements will need to be confirmed in later-stage trials.
Additionally, while the absence of treatment-related deaths and the manageable safety profile are positive, the presence of low-grade adverse events like fatigue, dysgeusia (altered taste) and nausea should not be overlooked as they can impact patient quality of life.
From a financial standpoint, the positive preliminary data from the ASPEN-07 trial is a significant development for ALX Oncology. An unconfirmed ORR of 59% surpasses the benchmark of PADCEV alone, indicating that evorpacept, when combined with existing treatments, could potentially offer a superior therapeutic option. This could translate to a competitive advantage in the immuno-oncology market, especially if these results are replicated in future, larger trials.
The fact that the combination therapy was well-tolerated and no maximum tolerated dose was reached is also promising. This could mean a smoother path through regulatory hurdles, reducing the risks associated with severe adverse events that can delay or derail drug development.
The market may react positively to this news, as it showcases the potential for a new, effective treatment in a patient population with significant unmet needs. However, investors should remain cautious and monitor upcoming results from later-phase trials to understand the full impact on ALX Oncology's pipeline and revenue projections. In the short term, this news may boost investor confidence and lead to increased stock activity.
Analyzing the broader market implications, the preliminary data from the ASPEN-07 trial taps into a niche yet significant segment of the oncology market—patients with advanced bladder cancer who have limited treatment options. A higher ORR of 59% compared to the benchmark 41% for PADCEV alone indicates a potentially superior treatment that could capture a significant market share if eventual approvals are secured.
The market for bladder cancer treatments is growing, driven by an aging population and advancements in oncology. A successful combination therapy not only enhances ALX Oncology's product portfolio but also strengthens its positioning against competitors in the immuno-oncology space. The absence of severe adverse events further adds to the product’s attractiveness, potentially leading to faster adoption post-approval.
However, the continuation and outcomes of Phase 2 and beyond will be critical. Successful data from these trials could solidify ALX Oncology's stance in the market and enhance its long-term growth prospects, making it an attractive target for partnerships or acquisitions by larger pharmaceutical companies.
- Evorpacept in combination with PADCEV®, an approved antibody-drug conjugate (“ADC”), demonstrated promising activity and was generally well tolerated
- Company to host conference call and webcast with Samuel A. Funt, M.D., of Memorial Sloan Kettering Cancer Center on Friday, June 7, 2024, at 1:00 PM ET
SOUTH SAN FRANCISCO, Calif., June 02, 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 presented data from its Phase 1 ASPEN-07 clinical trial in a poster presentation (abstract #4575) at the 2024 American Society of Cancer Oncology (“ASCO”) Annual Meeting being held in Chicago from May 31-June 4, 2024. These findings represent the first evorpacept combination data with an ADC from ASPEN-07’s ongoing, open-label, single-arm, clinical trial of evorpacept in combination with PADCEV (enfortumab vedotin or “EV”) in patients with locally advanced or metastatic urothelial cancer (“la/m UC”). Evorpacept is a CD47 blocker with an inactivated Fc effector domain that is designed to minimize associated toxicity.
Key results as of the data cut-off date of April 3, 2024:
Initial patient demographics
- Twenty-eight EV-naïve patients were enrolled with
29% having received three or more prior lines of therapy. - All patients had disease that progressed after platinum chemotherapy and checkpoint inhibition.
- Approximately
93% of patients had metastatic disease.
The combination was generally well-tolerated in a heavily pre-treated patient population
- No maximum tolerated dose was reached, and the maximum administered evorpacept dose was 30 mg/kg Q2W.
- There were no treatment-related deaths in the study.
- The most frequent adverse events due to any cause were low-grade fatigue, dysgeusia, nausea, diarrhea, hyperglycemia, and pruritis.
Initial activity showed tumor reduction in the majority of evaluable patients
- ASCO poster presentation data-cut reported an unconfirmed overall response rate (“ORR”) of
59% (n=22) with evorpacept plus EV (EV single agent ORR benchmark is41% 1). - Following the April data cut-off, four additional response evaluable patients yielded an unconfirmed ORR of
61% (n=26) including two confirmed complete responses and six confirmed partial responses.- To date,
58% of evaluable patients remain in the study.
- To date,
- Continued follow-up for patients who are EV-naïve on ASPEN-07 is ongoing and, enrollment of a new cohort of patients who have received prior EV has begun.
“We are encouraged by the preliminary safety data and clinical activity of evorpacept combined with PADCEV in patients with advanced bladder cancer,” said Sophia Randolph, M.D., Ph.D., Chief Medical Officer of ALX Oncology. “To our knowledge, these data are the first demonstration of anti-tumor activity with a CD47 blocker and an ADC in a heavily pre-treated patient population in the clinical setting. With these promising early results, we are evaluating clinical development options in both PADCEV-naïve and experienced patient populations.”
“This emerging dataset reported favorable potential for evorpacept to be combined with an ADC in a patient population that has exhausted many treatments,” said Jason Lettmann, Chief Executive Officer of ALX Oncology. “We are especially hopeful because of the two patients with confirmed complete responses, which further exhibited this combination is active and that responses could improve over time in more patients. Heading further into the year, we will continue the momentum for ASPEN-07 as we gear up to share multiple, randomized, Phase 2 clinical data readouts where evorpacept is combined with anti-cancer antibodies and checkpoint inhibitors.”
The poster can be found on the Publications section of the ALX Oncology website here.
Company Event with ASPEN-07 Principal Investigator and ALX Oncology Management
The Company is hosting a virtual event with key opinion leaders on Friday, June 7, 2024, at 1:00 PM ET. The event will feature leading ASPEN-07 principal investigator and bladder cancer expect, Samuel A. Funt, M.D., from Memorial Sloan Kettering Cancer Center, along with the management team of ALX Oncology. The discussion will cover details of the first promising initial dose escalation data from the Phase 1 ASPEN-07 clinical trial of evorpacept in combination with EV in patients with la/m UC, and how ASPEN-07 could fit into the treatment paradigm of this indication.
Samuel A. Funt, M.D., is a genitourinary oncologist at Memorial Sloan Kettering Cancer Center in New York, NY, where he is also Director of the Inpatient Genitourinary Oncology Service, Director of Bladder Cancer Clinical Trials Operations, and member of the Data Safety Monitoring Committee. Dr. Funt has practiced medicine and been involved in clinical trials for over 10 years. His top areas of clinical expertise are Bladder and Testicular Cancers. Dr. Funt has co-authored over 60 peer-reviewed articles and been awarded research grants from the National Institutes Health, American Society of Clinical Oncology, and the American Cancer Society. His research focuses on the development of more personalized and effective treatments and novel biomarkers of therapeutic response and resistance.
The event will be webcast live and can be accessed by visiting the Investors section of ALX Oncology’s website at www.alxoncology.com and selecting Events under News and Events. To participate in the live event, please register using this link: https://edge.media-server.com/mmc/p/ct2fpmxb. An archived webcast will be available following the event.
About the Phase 1 Clinical Trial Investigating Evorpacept plus EV in Advanced Bladder Cancer
The Phase 1 clinical trial is an ongoing, open-label, single arm is designed to evaluate the safety, tolerability, and efficacy of evorpacept in combination with EV in patients with la/m UC (NCT05524545). This dose escalation clinical trial has enrolled cohorts receiving 20 mg/kg Q2W or 30 mg/kg Q2W evorpacept plus standard EV treatment. The study is sponsored and conducted by ALX Oncology.
About Bladder Cancer and UC
As estimated by the National Cancer Institute, bladder cancer is the sixth most common cancer type in the United States. UC is the most common type of bladder cancer and accounts for approximately
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, 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 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 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.
References
- 1 Powles, et al, NEJM 2021; Powles, et al, Genitourinary Cancer Symposium 2021
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
What is the overall response rate (ORR) for the combination of evorpacept and PADCEV in the Phase 1 ASPEN-07 trial?
Were there any treatment-related deaths in the ASPEN-07 trial?
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