Immune Biomarker Assessment and Manufacturing Development for SQ3370-001, a first-in-human phase I dose-escalation clinical trial to test a novel treatment against advanced solid tumors

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Abstract In 2018, the global incidence of new cancer diagnoses was estimated at over 18 million cases, and cancer- related deaths were estimated at over 9.6 million. Of these cases, the vast majority were solid tumors, accounting for more than 16 million new cases and 8 million cancer deaths. This includes soft tissue sarcoma (STS), a heterogeneous group of aggressive malignant tumors that have a poor 5-year survival rate of only 65%. In the U.S., an estimated 13,000 people will be diagnosed with STS in 2020, and more than 5,000 will die of the disease. For patients diagnosed with STS, treatment often involves chemotherapy with a cytotoxic agent such as doxorubicin (Dox), an anthracycline that has been used to induce tumor regression in a variety of neoplastic conditions. Dox is also known to induce immunogenic cell death and enhance tumor responsiveness to immune checkpoint blockade therapies. Unfortunately, the extended use of Dox in patients is limited by severe toxic side effects—most notably irreversible cardiotoxicity and bone marrow suppression—which can be life threatening. Therefore, there is an immediate need for new methods to reduce the systemic toxicity and off-target effects of Dox while maintaining its antitumor efficacy Shasqi has developed SQ3370, a novel drug product that will improve the treatment of patients with injectable solid tumors undergoing doxorubicin (Dox)-based chemotherapy. Preclinical studies done to-date have shown that SQ3370 results in significant inhibition of tumor growth (both injected and non-injected tumors), immune activation, prolonged survival, and protection against tumor rechallenge, while exhibiting reduced systemic side effects compared to conventional Dox. Extensive preclinical data with SQ3370 has led to an open investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA). A Phase 1, first-in-human, dose-escalation study is currently enrolling, to evaluate the safety/tolerability, PK, and preliminary efficacy of SQ3370 in patients with locally advanced or metastatic solid tumors. This Direct-to-Phase-2 application has two main objectives: 1) To gain additional mechanistic insight of SQ3370 immune activation to support further clinical development; 2) To support both clinical and commercial development through manufacturing process optimization and stability studies, that is further described in 5 Specific Aims. These aims will accelerate development of SQ3370, a novel therapy that promises to ultimately result in improved treatment and outcomes for millions of patients with solid tumors.