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

NCT ID: NCT04106492

Last Updated: 2025-11-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-01
• Study Completion Date: 2023-09-07

Brief Summary

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

Conditions

Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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.

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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.

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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.

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

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

Group Type: EXPERIMENTAL

SQ3370

Intervention Type: DRUG

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

Interventions

SQ3370

SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

Intervention Type: DRUG

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shasqi, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jim Williams, MD

Role: STUDY_DIRECTOR

Shasqi, Inc.

Locations

City of Hope

Duarte, California, United States

Stanford Cancer Center

Palo Alto, California, United States

Sarcoma Oncology Center

Santa Monica, California, United States

Washington University in St. Louis

St Louis, Missouri, United States

Oregon Health & Science University

Portland, Oregon, United States

MD Anderson Cancer Center

Houston, Texas, United States

University of Washington

Seattle, Washington, United States

Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

Royal North Shore Hospital

Sydney, New South Wales, Australia

Cancer Research Institute

Adelaide, South Australia, Australia

Countries

United States; Australia

References

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.

Reference Type: DERIVED

PMID: 40522144 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37034617 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-0185

Identifier Type: OTHER

Identifier Source: secondary_id

SQ3370-001

Identifier Type: -

Identifier Source: org_study_id