Article Text

Download PDFPDF

404 ALX148, a CD47 blocker, in combination with standard chemotherapy and antibody regimens in patients with gastric/gastroesophageal junction (GC) cancer and head and neck squamous cell carcinoma (HNSCC)
  1. Keun-Wook Lee1,
  2. Hyun Chung2,
  3. Won Seog Kim3,
  4. Laura Chow4,
  5. Nehal Lakhani5,
  6. Wells Messersmith6,
  7. Yung-Jue Bang7,
  8. Patricia LoRusso8,
  9. Philip Fanning9,
  10. Pierre Squifflet10,
  11. Feng Jin9,
  12. Alison Forgie9,
  13. Hong Wan9,
  14. Jaume Pons9,
  15. Sophia Randolph9 and
  16. Justin Gainor11
  1. 1Seoul National University Hosp Bundang, Gyeonggi-do, Republic of Korea
  2. 2Yonsei Cancer Center, Seoul, Republic of Korea
  3. 3Samsung Medical Center, Seoul, Republic of Korea
  4. 4University of Washington, Seattle, WA, USA
  5. 5START Midwest, Grand Rapids, Michigan, USA
  6. 6University of Colorado Cancer Center, Aurora, CO, USA
  7. 7Seoul National University Hospital, Seoul, Republic of Korea
  8. 8Yale Cancer Center, New Haven, CT, USA
  9. 9ALX Oncology Inc., Burlingame, CA, USA
  10. 10International Drug Development Institute, Brussels, Belgium
  11. 11Massachusetts General Hosp, Cancer Ctr., Boston, MA, USA


Background CD47 is a myeloid checkpoint up-regulated by tumors to evade the anticancer immune response. ALX148 is a high affinity CD47-blocking fusion protein with an inactive Fc region designed to safely enhance anticancer therapeutics.1 2 ALX148 in combination with standard chemotherapy and antibody regimens was evaluated in patients (pts) with advanced HER2-positive GC or HNSCC.

Methods Pts with previously treated advanced HER2-positive GC or untreated advanced HNSCC received ALX148 (A) 10 mg/kg QW or 15 mg/kg QW in combination with trastuzumab (T) + ramucirumab (ram) + paclitaxel (pac) as 2nd or later-line treatment or pembrolizumab (P) + 5FU + platinum (cisplatin or carboplatin) as 1st line therapy, respectively. The primary endpoint was dose limiting toxicity (DLT). Tumor response, pharmacokinetic (PK), and pharmacodynamic (PD) markers were assessed in all pts. Preliminary data from enrolling cohorts, and follow-up data from pts with GC administered A+T, and with HNSCC administered A+P are also reported as of 30June2020.

Results Fifty-five pts enrolled into this portion of the study. Twelve patients with ≥2L GC received A+T+ram+pac and were evaluated for safety. No DLTs, were reported, and the ALX148 maximum administered dose was 15 mg/kg QW. Out of the 9 pts who experienced any adverse event, 7 pts reported treatment-related adverse events (TRAE). The most common TRAEs were low grade diarrhea, fatigue, pruritus and rash (each n=2,17%). Nine of the 12 patients were response-evaluable and reported a 66% ORR with 6PR and 3SD (including one ongoing near PR, ↓29.6%). Three patients with 1L HNSCC were administered A+P+5FU+platinum. No DLTs were reported and accrual to 15 mg/kg QW continues. Three pts experienced any AE, none were treatment-related. Of 3 evaluable patients with HNSCC, 2PR and 1SD were reported. Initial ALX148 combination PK and CD47 target occupancy are similar to that of single agent administration. Response duration and survival follow-up of 19 pts with HER2-positive GC administered A+T (2nd or later-line; 21% ORR) and of 10 pts with checkpoint inhibitor naïve HNSCC administered A+P (2nd or later-line; 40% ORR) will be reported. Results of all cohorts will be updated at time of presentation.

Conclusions Initial data suggests the myeloid checkpoint inhibitor, ALX148, is well tolerated in combination with the above anticancer antibodies, T-cell checkpoint inhibitor, and cytotoxic chemotherapy regimens with early anticancer signals in GC and HNSCC that compare favorably with historic controls. No MTD has been reached in any combination to date and accrual to chemotherapy combination regimens is ongoing.

Trial Registration ClinicalTrials. gov identifier NCT03013218

Ethics Approval The study was approved by all participating institutions’ Ethics and/or Review Boards


  1. Kauder S, Kuo T, Harrabi O, Chen A, Sangalang E, et al. ALX148 blocks CD47 and enhances innate and adaptive antitumor immunity with a favorable safety profile. PLoS ONE 2018;13(8).

  2. Chow L, Gainor J, Lakhani N, et al. A phase I study of ALX148, a CD47 blocker, in combination with standard anticancer antibodies and chemotherapy regimens in patients with advanced malignancy. Journal of Clinical Oncology 2020;38:15_suppl, 3056–3056.

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.