The novel checkpoint inhibitor, evorpacept induced responses in patients with head and neck squamous cell carcinoma and gastric cancer when used in combination with anticancer therapy and chemotherapy in a phase 1b study.
The addition of evorpacept (ALX148) to anticancer agents and chemotherapy has achieved promising and durable responses in patients with gastric or gastroesophageal junction (GEJ) cancer and head and neck squamous cell carcinoma (HNSCC) in the phase 1b ASPEN-01 clinical trial, according to findings presented during the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2021.1,2
Evorpacept is a high affinity, CD47-blocking, myeloid checkpoint inhibitor. The agent contains an inactive Fc region that can enhance anticancer therapies.
“These updated data provide growing support that evorpacept in combination with the standard regimens studied may translate into a meaningful survival benefit in patients with advanced HNSCC and GC who historically have poor outcomes,” said Keun-Wook Lee, MD, PhD, professor of Seoul National University College of Medicine and director of the Clinical Trials Center, Seoul National University Bundang Hospital, Seoul, Korea, in a press release.
ASPEN-01 is a phase 1, dose-escalation study (NCT03013218) in which the combination of evorpacept, anticancer regimens, and chemotherapy is being investigated in patients with advanced or metastatic solid tumors and relapsed or refractory non-Hodgkin lymphomas. Patients enrolled all had adequate bone marrow function, renal and liver function, and adequate performance status.
Eighteen patients were evaluable for response from the previously-treated HNSCC cohort, 13 from the checkpoint inhibitor-naïve HNSCC cohort, and 10 from the gastric cancer cohort at the data cutoff date of September 1, 2021.
At baseline, the patients with gastric cancer treated with evorpacept plus trastuzumab (Herceptin) and chemotherapy had a median age of 67.5 years (range, 36-83) and were largely male (n = 13), and Asian (n = 15). Most patients in the cohort had a performance score of 1 at baseline. Ninety-four percent of the group progressed upon prior anti-HER2 therapy, 11.1% progressed on greater than 2 prior lines of anti-HER2 therapy, and 11.1% progressed on prior treatment with a checkpoint inhibitor. There were also 15 patients in the cohort who have visceral distant metastasis.
In the HER2-positive gastric cancer cohort, patients were previously treated with up to 2 lines of therapy. The cohort was treated with evorpacept in combination with trastuzumab plus ramucirumab (Cyramza) and paclitaxel. The objective response rate (ORR) observed with the investigational combination was 72.2% with a 14.8-month median duration of response (mDOR).
The 12-month overall survival (OS) observed with the combination in previously treated patients with HER2-positive gastric cancer was 79%, and the median OS was 17.1 months
Baseline demographics for the HNSCC cohort treated with evorpacept plus pembrolizumab (Keytruda) and chemotherapy showed that patients had a median age of 61 years (range, 45-70), were predominantly male (n = 12), and Asian (n = 10). The majority of the cohort had a performance status of 0 and 54% had visceral distant metastasis.
The ORR in these patients was 38.5% which consisted of 1 complete response (CR), 4 partial responses (PRs), and 6 cases of stable disease (SD). The median progression-free survival was 5.6 months (95% CI, 3.6 to not reached), and the median OS was not reached. The estimated 12-month OS rate was 83.3%.1,2
No dose-limiting toxicities (DLTs) were observed in the previously-treated HNSCC cohort. The most common treatment-related adverse events (TRAEs) urticaria, rash, and diarrhea, which occurred in 17% of patients.2
In the CPI-naïve HNSCC population who also received evorpacept plus pembrolizumab and chemotherapy, the median age at baseline was 63 years (range, 35-81), and the group mainly consist of male patients (n = 7) who were predominantly Asian (n = 5). The performance status observed in most patients was 1 and 60% had visceral distant metastasis.
In CPI-naïve HNSCC population, long-term follow-up data from patients treated with evorpacept plus pembrolizumab showed a 12-month OS rate of 80% with a mOS of 24.5 months. In this cohort, no DLTs were reported with evorpacept being administered at 15 mg/kg once per week. The TRAEs observed in 7.7% of the cohort included pneumonitis, anemia, fatigue, neutropenia, and hypersensitivity reaction.1,2
“The consistency and predictive value of evorpacept’s emerging survival-based data in aggressive solid tumor diseases is highly encouraging,” said Sophia Randolph, MD, PhD, chief medical officer, ALX Oncology, in a press release.1 “We are excited to investigate the impact of evorpacept on these longer-term measures of clinical benefit in our randomized phase 2 programs in patients with HNSCC (ASPEN-03 and ASPEN-04) and GC (ASPEN-06).”
1. ALX oncology announces updated data from ongoing clinical trial (ASPEN-01) of evorpacept showing emerging clinical benefit in survival-based endpoints in patients with advanced solid tumors. News release. ALX Oncology. November 10, 2021. Accessed November 10, 2021.
2. Lee KW, Chung H, Kim TM, et al. 498 Evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) and with gastric/gastroesophageal cancer (GC); ASPEN-01. Presented at SITC Annual Meeting 2021; ; November 10-14 2021; Washington, DC. Abstract 498.