Evorpacept With Keytruda Did Not Elicit Responses in Head and Neck Cancer

Evorpacept and Keytruda didn’t meet the primary endpoints of the ASPEN-03 and ASPEN trials, in advanced head and neck squamous cell carcinoma.

Among patients with advanced head and neck squamous cell carcinoma (HNSCC), the combination of evorpacept and Keytruda (pembrolizumab) with or without chemotherapy failed to meet the primary endpoints of the phase 2 ASPEN-03 and ASPEN-04 clinical trials, ALX Oncology Holding Inc. has announced.

The combination failed to improve patients’ objective response rates (ORRs) as compared to the historical controls of Keytruda along and Keytruda with chemotherapy, respectively, as a first-line treatment in patients with advanced HNSCC, the company announced.

While the combination of evorpacept and Keytruda with or without chemotherapy in the ASPEN-03 and ASPEN-04 clinical trials demonstrated a manageable safety profile and was consistent with what had been previously reported for Keytruda and chemotherapy in this setting, the company stated that it will no longer pursue evorpacept in combination with Keytruda for the treatment of HNSCC. However, there are multiple clinical trials of evorpacept in combination with anti-cancer antibodies that will continue.

“While there were encouraging trends in ASPEN-03 in ORR versus the historical and internal control, we've decided not to pursue evorpacept and [Keytruda] in head and neck cancer in light of our prioritization of the more established anti-cancer antibody combination program based on multiple positive studies,” said Dr. Alan Sandler, Chief Medical Officer at ALX Oncology. “We are disappointed that these studies did not meet their primary endpoints, most importantly for the patients for whom current standard-of-care treatment approaches fall short, and we thank all who participated in the trials.”

“Moving forward, we are continuing to rapidly advance our clinical program combining evorpacept with anti-cancer antibodies supported by robust clinical data across trials in multiple tumor types. Evorpacept has demonstrated response rates and durability beyond what is expected from standard of care across several studies when combined with Herceptin (trastuzumab), zanidatamab and Rituxan (rituximab),” said Jason Lettmann, CEO at ALX Oncology. “Based on the positive data and strong mechanistic rationale, we maintain our confidence in the evorpacept clinical development program and intend to deliver on that promise with additional clinical data in breast cancer and colorectal cancer in the near-term. With evorpacept and ALX2004, our novel EGFR-targeted antibody-drug conjugate, we continue our commitment to bringing forth meaningful therapies for patients living with cancer.”

Evorpacept, as explained on the National Cancer Institute’s website, is a fusion protein, meaning it is a protein generated by joining parts of two different proteins, which may help the immune system destroy tumor cells.

According to the National Cancer Institute, the drug is currently being investigated in six clinical trials in disease types including oropharyngeal cancer, myeloma, urothelial carcinoma and gastric cancer.

The ASPEN-03 trial, according to its listing on clinicaltrials.gov, enrolled 189 patients, and evaluated evorpacept and Keytruda versus Keytruda alone among patients with advanced, recurrent HNSCC that was PD-L1 positive and who had not yet been treated for advanced cancer. The ASPEN-04 trial, according to the listing on clinicaltrials.gov, enrolled 172 patients and was a study of evorpacept with Keytruda and chemotherapy among patients with metastatic or unresectable, recurrent HNSCC who had not yet been treated for advanced disease.

Detailed findings from the ASPEN-03 and ASPEN-04 clinical trials will be submitted to a future medical meeting, according to the news release from ALX Oncology.

The United States Food and Drug Administration (FDA) has previously granted both fast track designation and orphan drug designation to evorpacept for the second-line treatment of patients with HER-2 positive gastric or GEJ carcinoma, according to the news release.

Fast track designation, as explained by the FDA on its website, is part of a process to facilitate the development and expedite the review of drugs that treat serious conditions and fulfill an unmet medical need, and orphan drug designation is granted to drugs or biological products to prevent, diagnose or treat a rare disease or condition.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.