Evorpacept (CD47 blocker) in sviluppo clinico in diverse indicazioni oncologiche (UC, AML, MDS, HNSCC, GC)

ALX Oncology Holdings Inc., (“ALX Oncology”), a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, announced clinical program updates for its lead program, evorpacept, a next generation CD47 blocker.

ASPEN-07, a Phase 1 Trial of Evorpacept for the Treatment of Patients with Urothelial Carcinoma (“UC”)

• ALX Oncology will initiate a new clinical study, ASPEN-07, to investigate evorpacept in combination with an antibody-drug conjugate (“ADC”), PADCEV® (enfortumab vedotin-ejfv), for the treatment of patients with urothelial carcinoma (“UC”) in the fourth quarter of 2022. Enfortumab vedotin-ejfv is an ADC directed to Nectin-4, a protein located on the surface of cells that is highly expressed in UC.
• In April 2022, ALX Oncology successfully completed a pre-IND consultation with the U.S. Food and Drug Administration (“FDA”) for a Phase 1 study of evorpacept in combination with enfortumab vedotin-ejfv in patients with previously treated locally advanced or metastatic UC.
• The IND application for ASPEN-07 was submitted to the FDA in May 2022.

ASPEN-05, a Phase 1 / 2 Clinical Trial of Evorpacept in Combination with Venetoclax and Azacitidine in Acute Myeloid Leukemia (“AML”), and ASPEN-02, a Phase 1/2 Study of Evorpacept in Combination with Azacitidine in Myelodysplastic Syndrome (“MDS”)

• The Phase 1 dose escalation portion of ASPEN-05 has successfully completed enrollment with no safety concerns to date up to the highest protocol defined dose level of 60 mg/kg evorpacept once every four weeks. This portion of the study is designed to characterize the initial safety of evorpacept in combination with venetoclax and azacitidine for the treatment of patients with relapsed/refractory AML and previously untreated AML who are not candidates for intensive induction therapy.
• Patient enrollment will be paused before proceeding into the Phase 1 dose optimization portion of ASPEN-05 pending completion of the Phase 1 portion of ASPEN-02, a Phase 1/2 study of evorpacept in combination with azacitidine in patients with MDS. Data from ASPEN-02 will be used to inform the optimal dose(s) of evorpacept to be studied in the ASPEN-05 study in combination with venetoclax and azacitidine. Ongoing patients in ASPEN-05 will continue to be treated and followed per protocol.
• MDS and AML are indications where evorpacept possesses a similar mechanism of action, and this strategy allows us to evaluate evorpacept in a cost-efficient manner in patients with AML while maintaining our focus in our solid tumor programs. We anticipate preliminary dose escalation data from ASPEN-05 to be presented at a scientific conference in 2022, and initial dose optimization data from ASPEN-02 to be presented at a scientific conference in mid-2023.

ASPEN-03 and ASPEN-04, which are two distinct randomized Phase 2 studies for the treatment of patients with advanced head and neck squamous cell carcinoma (“HNSCC”)

• ALX Oncology continues to advance evorpacept in two randomized Phase 2 studies in patients with HNSCC in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, with or without chemotherapy. Both studies are being conducted in collaboration with Merck, known as MSD outside the United States and Canada.
• The first study, ASPEN-03, is evaluating the efficacy of evorpacept in combination with pembrolizumab for the first-line (“1L”) treatment of patients with PD-L1 expressing metastatic or unresectable, recurrent HNSCC with a Combined Positive Score (“CPS”) ≥ 1.
• The second study, ASPEN-04, is investigating evorpacept in combination with pembrolizumab and standard chemotherapy for the 1L treatment of patients with metastatic or unresectable, recurrent HNSCC (any CPS value).
• Patient enrollment for ASPEN-03 and ASPEN-04 continues as planned with results expected to be presented by mid-2024.

ASPEN-06, a Phase 2/3 Study of Evorpacept for the Treatment of Patients with Advanced Gastric or Gastroesophageal Junction (“GEJ”) Cancer

• ASPEN-06 is a randomized Phase 2 (open-label) / Phase 3 (double-blind), international, multi-center study to evaluate the efficacy of evorpacept and CYRAMZA® (ramucirumab) added to trastuzumab and paclitaxel for the treatment of patients with HER-positive gastric/GEJ cancer whose tumors have progressed following treatment with HER2-targeted therapy and chemotherapy. ASPEN-06 is being conducted in collaboration with Eli Lilly and Company.
• In March 2022, the first patient was dosed in the Phase 2/3 ASPEN-06 study.
• Patient enrollment continues to progress and results from the Phase 2 portion of ASPEN-06 are expected to be presented in 2023.

source: press release