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 - 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.
