Abstract CT177: SQ3370 in advanced solid tumors: Interim phase 1 results

Abstract Background: SQ3370, a novel therapy, utilizes Shasqi’s proprietary Click Activated Protodrugs Against Cancer (CAPAC) platform where mutually-reactive click chemistry groups release Doxorubicin (Dox) at the tumor site while minimizing systemic exposure. In animals, SQ3370 enhanced T-cell infiltration, survival, and showed activity in both injected and non-injected lesions. Minimal to no toxicity, including no cardiotoxicity was seen in up to 9-fold dose increases in animals. Conventional Dox can induce cardiomyopathy with incidences of 6-20% for cumulative doses of 500 mg/m2 in humans. Here we report interim results of the Phase 1 trial (SQ3370-001; NCT04106492). Methods: SQ3370 has 2 components: 1) Intratumoral injection of a protodrug-activating biopolymer (SQL70); 2) then 5 consecutive daily IV infusions of an attenuated protodrug of Dox (SQP33). Key criteria for enrollment include locally advanced to metastatic solid tumors, ≤300 mg/m2 prior exposure to DOX, ECOG status 0 or 1, and no limit to the number of prior systemic therapies. Primary objectives include safety and determining Phase 2 dose. Dose escalation was assessed in 2 stages: 1) accelerated titration; 2) 3+3 design. Dose-limiting toxicity (DLT) was evaluated in cycle 1. Results: As of 26NOV2021 data cut, 17 patients (pts) in 8 dose escalation cohorts have been enrolled. MTD has not been reached. Median age was 59 years (26-79), 53% were females, and were ECOG 1 (59%). Prior procedures included surgery (82%) and radiation (47%). At study entry, 82% of pts had metastases with a median number of metastatic sites being 2 (1-5). Solid tumors were sarcoma (65%), and cancers of the skin, breast, and gynecologic organs were 12% for each, respectively. Sixteen of 17 (94%) pts received prior chemotherapy with 47% receiving prior Dox. Median number of prior systemic therapies was 2 (1-7). Intratumoral injection sites include soft tissue and chest wall. Of the 17 pts, 65% received >500 mg/m2, 53% (>1000), and 29% (>2000) cumulative Dox given as SQP33. Median duration of treatment was 3 cycles (1-10). No DLTs were observed. Most frequent AEs, regardless of causality, included nausea (n = 9), fatigue (n = 6) and anemia (n = 5). No signs of cardiomyopathy were seen in pts with an echo performed within 1 mo. of study start. Although >50% of pts received >1000 mg/m2, ejection fraction (LVEF) remained normal. No AEs that led to discontinuation or death were related to SQ3370. All pts were evaluable for response. At a median follow-up of 10 wks (4-30), 65% of pts had SD as best response. Median duration of SD was 80 days (37-186) with 64% sustaining SD for ≥60 days, corresponding to an overall disease control rate of 65%. The remainder of pts had PD as best response. Over 35% of pts remain on drug. Conclusions: SQ3370 was well tolerated. No DLTs and normal LVEF were seen with pts receiving >1000 mg/m2 Dox cumulative doses. Dose escalation is ongoing. Preliminary evidence of disease control was observed in this heavily pre-treated, high cancer burden, solid tumor pt population. Citation Format: Sant P. Chawla, Kathleen Batty, Vivek Bhadri, Nam Bui, Alexander D. Guminski, Jose M. Mejia Oneto, Sangeetha Srinivasan, James F. Strauss, Vivek Subbiah, Mia C. Weiss, Rosalind Wilson, Nathan A. Yee, Michael Zacharian, Vineet Kwatra. SQ3370 in advanced solid tumors: Interim phase 1 results [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT177.