FDA Grants 2 Fast Track Designations for ALX148

The FDA granted 2 Fast Track designations for ALX148 for the first-line treatment of patients with head and neck squamous cell carcinoma (HNSCC), and for the second-line treatment of patients with HER2-positive gastric or gastroesophageal junction (gastric/GEJ) carcinoma, according to ALX Oncology, the agent’s developer.¹

These Fast Track designations are based on data from an ongoing, open-label, multicenter phase I clinical trial of ALX148 in combination with pembrolizumab (Keytruda) or trastuzumab (Herceptin). 

“This designation reflects the potential for ALX148 to be an important advancement in the treatment of patients with HNSCC and HER2-positive gastric/GEJ cancer,” Sophia Randolph, MD, PhD, chief medical officer of ALX Oncology, said in a press release. “We look forward to working closely with the FDA on the clinical development of ALX148 for patients with cancer.”

The phase I protocol for the phase I clinical study includes 2 parts, one being a single agent dose escalation phase and the other being a combination therapy phase. Part 2 includes an initial dose escalation portion followed by a dose expansion portion. Overall, 184 adult patients are anticipated to be enrolled in the study. 

Data from this trial were presented at the 2019 Society for Immunotherapy of Cancer (SITC) Annual Meeting. As of the data cutoff of September 23, 2019, 82 patients with advanced malignancies were treated with ALX148 in combination with standard regimens of either trastuzumab (n = 30) or pembrolizumab (n = 52).² There were 19 patients with HER2-positive G/GEJ whose tumors had progressed on prior systemic therapy, including HER2-targeted therapy, and 20 patients with HNSCC whose tumors had progressed on prior platinum therapy. 

Of the HER2 positive G/GEJ cohort, patients demonstrated an objective response rate (ORR) of 21% and a disease control rate (DCR) of 26%. Those in the HNSCC cohort demonstrated an ORR of 20% and a DCR of 30%, however, in checkpoint inhibitor naïve subjects (n = 10), an OOR of 40% and a DCR of 40% were observed.

ALX148 was well tolerated, with no maximum tolerated dose reached and treatment-related adverse events were predominately of low grade and frequency. Additionally, complete CD47 target occupancy was observed by the researchers throughout the dosing interval, with no impact indicated on circulating immune cell populations following ALX148 combination treatments. 

“These exciting clinical responses and pharmacodynamic changes within the tumor microenvironment observed with ALX148 combinations support our hypothesis that blocking CD47 with an Fc-inactive molecule can enhance the anti-cancer innate and adaptive immune response in patients with advanced solid tumor malignancies,” Jaume Pons, PhD, president and chief executive officer of ALX Oncology, said in a press release. “ALX148 as a checkpoint inhibitor has the potential to become a new cornerstone of immune therapy. We continue to advance ALX148 development in populations in need of novel treatments.”

References:

1. ALX Oncology’s ALX148 Receives Two Fast Track Designations from FDA for the Treatment of Patients with Head and Neck Squamous Cell Carcinoma and Patients with Gastric or Gastroesophageal Junction Adenocarcinoma [news release]. Dublin, Ireland & Burlingame, California. Published February 18, 2020. businesswire.com/news/home/20200218005233/en/ALX-Oncology’s-ALX148-Receives-Fast-Track-Designations. Accessed February 18, 2020. 

2. ALX Oncology Presents Clinical Biomarker Data from ALX148 Clinical Trial Solid Tumor Combination Cohorts at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) [news release]. Dublin, Ireland & Burlingame, California. Published November 6, 2019. businesswire.com/news/home/20191106005224/en/%C2%A0ALX-Oncology-Presents-Clinical-Biomarker-Data-ALX148. Accessed February 18, 2020.