1499P - Phase I clinical & immunologic data of SQ3370 in advanced solid tumors

Background

SQ3370 utilizes a proprietary Click Activated Protodrugs Against Cancer platform where mutually-reactive click chemistry groups release doxorubicin (Dox) at the tumor. Dox re-treatment (Tx) is associated with cumulative Dox toxicity and is less effective (response rates ≤10%) in heavily pre-treated (tx’d) patients (pts). SQ3370-tx’d animals show minimal to no toxicity, enhanced T-cell infiltration and survival, suggesting SQ3370 promotes antitumor immune responses.

Methods

SQ3370 has 2 components: 1) Intratumoral injection of a protodrug-activating biopolymer (bp) (SQL70: 10 or 20 mL); 2) 5 QD infusions of Dox protodrug (SQP33). Eligibility: advanced solid tumors, ≤300 mg/m2 prior Dox and no limit to prior therapies. Objectives: safety, Phase 2 dose and immune response by peripheral blood mass cytometry (CyTOF) and tumor multiplex immunohistochemistry (mIHC) at Cycles (C) 1, 2 & 3.

Results

As of 31JAN2022, 26 pts were tx’d, 21 with 10 mL bp and 5 with 20 mL bp at 8 dose levels of SQP33, currently at 12x Dox clinical dose. MTD was not reached. Median age: 61 yrs (26-84). Most pts had sarcoma (73%) and metastases (77%). Median prior systemic therapies received were 2 (1-7) in 92% and prior Dox in 50%. Median Tx duration was 2 cycles (1-12). Frequent AEs; bp group: 10 mL - nausea (n= 11) and fatigue (n= 9); 20 mL - anemia (n= 3) and nausea (n= 2). At a median follow-up of 9.2 wks, 21 pts were evaluable. Best response was SD in 71%. Disease control rate (CR+ PR+ SD ≥ 60days) was 43%. Pts evaluable for CyTOF (n=17) and mIHC (n=13), showed immunologic changes indicative of anti-tumor immune responses and apoptosis. Table: 1499P

Mann-Whitney U test comparing immune cells between cycles

Conclusions

SQ3370 with 10 or 20 mL bp was well tolerated in pts with 50% re-tx’d with Dox. Disease control was seen despite heavy prior treatment. Immunologic changes were consistent with a shift from immune suppressive to T cell permissive environments promoting cancer cell death. Dose escalation is ongoing..

Clinical trial identification

NCT04106492.

Editorial acknowledgement

Legal entity responsible for the study

Shasqi, Inc.

Funding

Shasqi, Inc.

Disclosure

S.P. Chawla: Financial Interests, Institutional, Principal Investigator: Shasqi inc. K. Batty: Financial Interests, Institutional, Principal Investigator: Shasqi inc. M. Alečković: Financial Interests, Personal, Full or part-time Employment: Shasqi, Inc.; Financial Interests, Personal, Stocks/Shares: Shasqi, Inc.. V.A. Bhadri: Financial Interests, Personal, Invited Speaker, Presentation - teaching session: Eisai. N. Bui: Financial Interests, Institutional, Principal Investigator: Shasqi inc. A. Guminski: Financial Interests, Institutional, Principal Investigator: Shasqi inc. J.M. Mejía Oneto: Financial Interests, Personal, Other, Founder and CEO of Shasqi: Shasqi; Financial Interests, Personal, Full or part-time Employment, Founder and CEO of Shasqi: Shasqi, inc; Financial Interests, Personal, Stocks/Shares, Founder and CEO of Shasqi: Shasqi; Financial Interests, Personal, Royalties, Founder and CEO of Shasqi: University of California; Non-Financial Interests, Invited Speaker, Founder and CEO of Shasqi: Shasqi; Non-Financial Interests, , Member: ASCO, AACR. S. Srinivasan: Financial Interests, Personal, Full or part-time Employment: Shasqi inc; Financial Interests, Personal, Stocks/Shares: Shasqi inc. J. Strauss: Financial Interests, Institutional, Principal Investigator: Shasqi inc. V. Subbiah: Financial Interests, Personal, Advisory Board, One time advisory board: Incyte, Novartis, Eli Lilly/ Loxo Oncology; Financial Interests, Personal, Advisory Board, One time ad board: Roche, Pfizer; Financial Interests, Personal, Advisory Board, Ad hoc advisory board: Relay Therapeutics; Financial Interests, Institutional, Invited Speaker, Research funding to conduct Clinical trial: Eli Lilly/Loxo Oncology, Blueprint medicines, Novartis, Boston Pharmaceuticals, Pfizer, Turning Point Therapeutics, Amgen, Bayer, Roche/ Genentech, Exelixis, Berg Pharma, N W Biotherapeutics, Relay Therapeutics, Abbvie, Agensys, Inhibrx, Dragonfly therapeutics, Takeda; Financial Interests, Institutional, Invited Speaker, Research funding to conduct clinical trial: Shasqi; Other, , Other, I am employed at the University of Texas MD Anderson Cancer Center: The University of Texas MD Anderson Cancer Center; Other, , Other, I receive research funding from NCI: National Cancer Institute, USA. M.C. Weiss: Financial Interests, Institutional, Principal Investigator: Shasqi inc. R. Wilson: Financial Interests, Personal, Other, Consultant: Shasqi inc. N. Yee: Financial Interests, Personal, Full or part-time Employment, Receive compensation for contracted work through Shasqi, Inc related to the development of a click activated protodrug platform for cancer treatment.: Shasqi, Inc.; Financial Interests, Personal, Full or part-time Employment, Receive compensation as an FTE of Tambo, Inc related to the development of a click activated protodrug platform: Tambo, Inc.; Financial Interests, Personal, Stocks/Shares, Stockholder of Shasqi, Inc.: Shasqi, Inc.; Financial Interests, Personal, Stocks/Shares, Stockholder of Tambo, Inc.: Tambo, Inc. M. Zakharian: Financial Interests, Personal, Full or part-time Employment: Shasqi; Financial Interests, Personal, Stocks/Shares: Shasqi. V. Kwatra: Financial Interests, Institutional, Principal Investigator: Shasqi inc.