Phase 1/2a Study of SQ3370 in Patients With Advanced Solid Tumors

A Multicenter Phase 1/2a, Open-Label Study of SQ3370 in Patients With Advanced Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, and preliminary activity of SQ3370 in patients with advanced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Cancer
• Intervention / Treatment: Drug: SQ3370

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris O'Brien Lifehouse
    • Sydney, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Cancer Research Institute
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Palo Alto, California, United States, 94304
      • Stanford Cancer Center
    • Santa Monica, California, United States, 90403
      • Sarcoma Oncology Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University in St. Louis
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Phase 1: Inclusion Criteria:

1. Diagnosis of advanced soft tissue sarcoma or other solid tumors
2. Adequate hematologic, hepatic, renal, and coagulation function
3. ECOG performance status score 0-1
4. Tumor is the type where published clinical data would suggest that anthracyclines have cytotoxic activity
5. Injectable tumor present

Phase 1: Exclusion Criteria:

1. Prior exposure to 300 mg/m^2 of Dox HCl or DOXIL / CAELYX ® or 600 mg/m^2 of Epirubicin HCl
2. Congestive heart failure (CHF), severe myocardial insufficiency, or cardiac arrhythmia

3. Any of the following within 28 days prior to Cycle 1 Day 1:

   • Major surgery, as defined by the Investigator
   • Radiotherapy
   • Chemotherapy, immunotherapy and/or anticancer therapy (except for small molecule kinase inhibitors, which are 6 elimination half-lives)
4. Trastuzumab or trastuzumab emtansine dosed within 7 months prior to Cycle 1 Day 1.
5. Any transfusion within 14 days prior to Cycle 1 Day 1.
6. Pregnant or breast-feeding women.
7. Known active CNS metastases and/or carcinomatous meningitis or symptomatic brain metastasis. Participants with previously treated brain metastases may participate provided they are radiologically stable
8. History of allergic reactions attributed to Dox or other anthracyclines, NaHA, hyaluronic acid, or gram-positive bacterial proteins
9. History or evidence of clinically unstable/uncontrolled disorder, condition, or disease

Phase 2a Expansion Group 1 (Extremity STS): Inclusion

1. Patients with unresectable soft tissue sarcomas of the extremity AJCC Stage III OR select IV (=>5 cm injectable tumors) locally advanced and or metastatic, not amendable to primary surgical intervention according to the consensus of a multidisciplinary treatment team, determined prior to screening.
2. High grade STS, Grade 2/3, with an assessable/injectable lesion of at least diameter ≥5 cm by RECIST 1.1 criteria
3. No prior chemotherapy for STS, or radiation to affected limb

Phase 2a Expansion Group 1 (Extremity STS): Exclusion

1. Uncontrolled pain related to tumor
2. Open wounds or tissue necrosis related to tumor mass
3. Compartment syndrome or impending compartment syndrome

Phase 2a Expansion Group 2 (Unresectable STS): Inclusion

1. Locally advanced or metastatic, unresectable, soft-tissue sarcoma of intermediate or high grade with measurable disease.
2. Life expectancy >12 weeks (about 3 month)

Phase 2a Expansion Group 2 (Unresectable STS): Exclusion

1. Prior exposure to anthracyclines
2. Treatment naive extremity tumors

Phase 2a Expansion Group 3a (Head and Neck): Inclusion

1. Patients with histologically or cytologically confirmed squamous-cell carcinoma of the head and neck (HNSCC) who meet any of the following a) confirmed relapsed HNSCC or b) metastatic at initial presentation HNSCC
2. Patients who may have received two or less systemic regimens (therapies include chemotherapy and/or immunotherapy)

Phase 2a Expansion Group 3a (Head and Neck): Exclusion

1. Airway obstruction by tumor mass that requires clinical intervention
2. Prior treatment with anthracyclines

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

15

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Cohort 1 (10 mL SQL70 and 8 mg/m^2 of SQP33); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 8 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Dose Escalation Cohort 2 (10 mL SQL70 and 16 mg/m^2 of SQP33); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 16 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors.	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Dose Escalation Cohort 3 (10 mL SQL70 and 32 mg/m^2 of SQP33); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 32 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors.	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Dose Escalation Cohort 4 (10 mL SQL70 and 58 mg/m^2 of SQP33); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 58 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors.	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Dose Escalation Cohort 5 (10 mL SQL70 and 85 mg/m^2 of SQP33); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 85 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Dose Escalation Cohort 6 (10 mL SQL70 and 125 mg/m^2 of SQP33); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 125 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Dose Escalation Cohort 7 (10 mL SQL70 and 185 mg/m^2 of SQP33); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 185 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Dose Escalation Cohort 8 (10 mL SQL70 and 250 mg/m^2 of SQP33); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 250 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Dose Escalation Cohort 9 (10 mL SQL70 and 315 mg/m^2 of SQP33); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 315 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Dose Escalation Cohort (20 mL SQL70 and 85 mg/m^2 of SQP33); 20 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 85 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Dose Escalation Cohort (20 mL SQL70 and 125 mg/m^2 of SQP33); 20 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 125 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: Cohort A (10 mL SQL70 and 185 mg/m^2 of SQP33); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 185 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced or metastatic solid tumors	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: P2a Group 1 (Extremity STS) (20 mL SQL70 and 250 mg/m^2/Day of SQP33); 20 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 250 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with soft tissue sarcomas of the extremity	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: P2a Group 2 (10 mL SQL70 and 500 mg/m^2/ of SQP33 for 2 days and and 250 mg/m^2/ of SQP33 for 1 day); 10 mL of SQL70 injected intratumorally on Day 1 of each 21-day cycle into a single lesion with 500 mg/m^2 of SQP33 infused on Day 1 and 2 with 250 mg/m^2 of SQP33 infused on each Day 3 in subjects with locally advanced, unresectable or metastatic soft tissue sarcomas who are anthracycline naïve	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin
Experimental: P2a Group 2 (10 mL SQL70 and 250 mg/m^2/day of SQP33 for five days); 10 mL of SQL70 injected intratumorally on Day with 250 mg/m^2 of SQP33 infused each day on Day 1 through Day 5 in subjects with locally advanced, unresectable or metastatic soft tissue sarcomas who are anthracycline naïve	Drug: SQ3370; SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 Cohorts	To determine the Recommended Phase 2 Dose of SQ3370	From start of treatment to approximately 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2a: Objective Response Rate (ORR)	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	Up to 1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate level of SQP33 in tumor	To determine the level of SQP33 protodrug and active Doxorubicin in tumor tissue	From start of treatment to approximately 12 weeks
Evaluate Pharmacodynamics (PD)	To assess immune response (changes in immune biomarkers) as assessed by PBMCs	From start of treatment to approximately 12 weeks

Collaborators and Investigators

• Sponsor: Shasqi, Inc.
• Investigators: Study Director: Jim Williams, MD, Shasqi, Inc.

Publications and helpful links

General Publications

• Srinivasan S, Yee NA, Aleckovic M, Zakharian M, Mahmoodi A, Wagner S, Nguyen TH, Chawla SP, Guminski AD, Mejia Oneto JM. Development of a First-in-Class Click Chemistry-Based Cancer Therapeutic, from Preclinical Evaluation to a First-in-Human Dose Escalation Clinical Trial. Clin Cancer Res. 2025 Sep 2;31(17):3662-3677. doi: 10.1158/1078-0432.CCR-24-2539.
• Srinivasan S, Yee NA, Zakharian M, Aleckovic M, Mahmoodi A, Nguyen TH, Mejia Oneto JM. SQ3370, the first clinical click chemistry-activated cancer therapeutic, shows safety in humans and translatability across species. bioRxiv [Preprint]. 2023 Mar 29:2023.03.28.534654. doi: 10.1101/2023.03.28.534654.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2020
• Primary Completion (Actual): September 7, 2023
• Study Completion (Actual): September 7, 2023

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: September 25, 2019
• First Posted (Actual): September 27, 2019

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: October 30, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Cancer; Head and Neck Cancer; Lung Cancer; Anthracycline; Phase 1; Doxorubicin; Ovarian Cancer; Solid Tumor; Sarcoma; Intratumoral; Soft Tissue Sarcoma; Tumor; Uterine Cancer; Precision Oncology; Precision Chemotherapy; Local Cancer Therapy; Targeted Cancer Therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Neoplasms by Histologic Type; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Neoplasms, Connective and Soft Tissue; Neoplasms; Lung Neoplasms; Ovarian Neoplasms; Head and Neck Neoplasms; Sarcoma; Uterine Neoplasms
• Other Study ID Numbers: SQ3370-001; 2020-0185 (Other Identifier: MD Anderson Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No