ALX Oncology's Evorpacept (ALX148), a novel CD47 inhibitor, is gaining traction as a potential treatment for HER2-positive gastric and gastroesophageal junction (GEJ) cancer. The ASPEN-06 Phase 2 trial results indicate that Evorpacept, when combined with trastuzumab, ramucirumab, and paclitaxel (TRP), demonstrates promising efficacy, warranting further investigation. This development addresses a critical unmet need in advanced gastric cancer therapy, where current treatments often yield limited response rates and overall survival.
Evorpacept: A Novel CD47 Inhibitor
Evorpacept distinguishes itself from standard CD47 inhibitors through its inactive Fragment crystallizable (Fc) domain. This design minimizes undesired immune activation and inflammation, reducing side effects typically associated with targeting healthy cells, such as red blood cells. Clinical trials have demonstrated a favorable safety profile in over 500 patients, highlighting the potential for improved tolerability compared to other CD47-targeting agents.
ASPEN-06 Trial Results
The ASPEN-06 Phase 2 trial evaluated Evorpacept in combination with TRP in patients with HER2-positive gastric and GEJ cancer who had prior lines of therapy with anti-HER2 agents. The results were compared against Trastuzumab Deruxtecan (Enhertu) from the DESTINY-Gastric01 study, an already FDA-approved antibody-drug conjugate developed by Daiichi Sankyo and AstraZeneca, which is a standard of care for this disease. The overall response rate (ORR) of Evorpacept with TRP was 40.3%, compared to 26.6% for TRP alone. Trastuzumab Deruxtecan presented an ORR of 40.5% in the DESTINY-Gastric01 study, showing similar initial tumor response rates between Evorpacept and Enhertu. Notably, in patients with fresh HER2-positive biopsies, the combination of Evorpacept plus TRP presented a higher ORR of 54.8%, outperforming the TRP-only cohort, which showed an ORR of 23.1%.
Duration of Response
In addition to comparable ORR, the Evorpacept combination demonstrated a longer median duration of response (DOR) of 15.7 months, compared to Enhertu's 11.3 months and TRP alone's 7.6 months. This suggests that Evorpacept plus TRP not only initiates a similar tumor response but also sustains it for a more extended period, potentially leading to improved clinical outcomes.
Market and Financial Considerations
ALX Oncology's current market capitalization is $110.6 million, and the company's balance sheet indicates that it is trading below its cash value. The company has $15.5 million in cash and equivalents and $141.2 million in short-term investments. The global gastric cancer market is forecasted to reach $10.7 billion by 2031, presenting a significant opportunity for Evorpacept if it secures FDA approval. The company anticipates initiating Phase 3 trials for Evorpacept in 2025, with potential FDA approval by 2026 or early 2027, assuming positive trial outcomes.
Future Outlook
While ALX Oncology faces potential dilution risks and requires successful trial outcomes to secure its financial future, the promising Phase 2 data and the potential of Evorpacept as a next-generation CD47 blocker make it a compelling candidate in the immuno-oncology space. The company's pipeline includes various combinations of Evorpacept with other cancer therapies, further expanding its potential applications and market reach.
