EA7222 – A Randomized Phase III Trial of Doxorubicin + Pembrolizumab Versus Doxorubicin Alone for the Treatment of Undifferentiated Pleomorphic Sarcoma (UPS) and Related Poorly Differentiated Sarcomas

The study chair for this trial is Seth Pollack, MD (Northwestern University/Robert H. Lurie Comprehensive Cancer Center). The community co-chair is Richard F. Reidel, MD (Duke University Medical Center).

Soft tissue sarcoma (STS) is a rare cancer that occurs in approximately 14,000 people in the United States each year. The current standard of care for patients with metastatic STS is chemotherapy, usually doxorubicin. Sometimes, the combination of doxorubicin and ifosfamide chemotherapy is used, as it was shown to produce improved response rates and better progression-free survival (PFS). However, this combination also increases toxicity and has not been shown to provide an overall survival benefit.

Early research suggests a potential role for immunotherapy in treating patients with metastatic undifferentiated pleomorphic sarcoma (UPS), representing about 20% of all STS cases. An exploratory early-phase trial of doxorubicin combined with the PD-1 inhibitor pembrolizumab in patients with metastatic STS resulted in promising response, tumor regression, and disease stability rates, particularly in patients with UPS. A separate, single-arm phase 2 trial of doxorubicin and pembrolizumab confirmed the tolerability of the regimen and showed several highly durable responses.

The EA7222 study is a randomized phase 3 trial of doxorubicin alone or in combination with pembrolizumab in patients with advanced UPS and related poorly differentiated sarcomas that cannot be removed by surgery (unresectable). Patients must not have previously received treatment with an anthracycline-based chemotherapy or with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA4 agent.

The study’s primary objective is to assess whether the combination therapy will improve PFS for this patient population. EA7222 is the second trial to activate from the ECOG-ACRIN Sarcoma Working Group, following EA7211/STRASS 2, which opened in August 2023.

EA7222 will enroll approximately 180 participants. Patients randomized to Arm A will receive six 3-week cycles of doxorubicin plus pembrolizumab, then continue receiving pembrolizumab until progression, unacceptable side effects, or up to completion of 2 years of therapy. Patients randomized to Arm B will receive six 3-week cycles of doxorubicin, then be monitored off treatment for up to 2 years. Patients randomized to receive doxorubicin on Arm B whose cancer progresses will be encouraged to switch and receive pembrolizumab as a single agent for up to 2 years.