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11555 Background: Shasqi is a clinical stage biotech that uses click chemistry, a Nobel Prize winning technology, to selectively activate cancer treatments at the tumor. The Click Activated Protodrugs Against Cancer (CAPAC) platform comprises of 1) tumor targeting agents, which carry an activator, and 2) attenuated cancer drugs, which are selectively activated at the tumor by the targeting agent through click chemistry, maximizing therapeutic index and minimizing toxicities. We have demonstrated clinical proof of concept with SQ3370, which uses an intratumorally injected SQL70 biopolymer (bp) with a doxorubicin (Dox) protodrug (SQP33) injected systemically. As previously reported RP2D of SQP33=12x Dox. (NCT04106492). Methods: Dox naïve patients (pts) received 10/20 mL bp and protodrug IV QD x 3 or 5. Key eligibility: locally advanced or metastatic soft tissue sarcomas (STS). The objective was to explore bp dose and schedule of the RDP2 (same dose per cycle) in advanced or metastatic STS. Results: Fourteen patients with predominantly metastatic (11/14) STS, all unresectable, were enrolled at the 1st interim analysis. Median age 58 years (32-89), ECOG=1 (11/14). Therapy was well tolerated. The most common TEAE was nausea and fatigue (all grade ≤ 2), with 1 subject in each group having a manageable grade ≤ 3 TEAE-related discontinuations. The majority of subjects did not suffer clinical myelosuppression grade ≤ 1 neutropenia (10/14), anemia (13/14), or thrombocytopenia (13/14), with DCR 71% (CI 95% 44-92%) and ORR 14.3% (CI 95%1.7-40%). Detailed PK, immune assessment and safety findings will be presented. Conclusions: SQ3370 is the first clinical click chemistry-based cancer therapy, and this is the 1st clinical trial to explore doses greater than 3x Dox in STS patients. The results show that the bp activates protodrug, which is not a vesicant, and releases Dox in patients. Click chemistry favorably alters PK and safety of the Dox payload. At 12x Dox, using the commonly administered 3-week schedule, Dox was very well tolerated. Click-chemistry maintains expected clinical activity, and preliminary data suggest enhanced safety (reduced myelosuppression) as well as unlocking immunological effects (intratumoral and systemic), without the myelosuppressive effects typically seen with Dox. Clinical trial information: NCT04106492 . Table: see text
Bui et al. (Sat,) studied this question.