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

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ClinicalTrials.gov Identifier: NCT04106492
Recruitment Status : Recruiting
First Posted : September 27, 2019
Last Update Posted : September 21, 2022
Sponsor:
Information provided by (Responsible Party):
Shasqi, Inc.

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

Condition or disease Intervention/treatment Phase
Cancer Drug: SQ3370 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 145 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Phase 1 dose escalation part of the study was done sequentially. The Phase 2 part of the study will be done in parallel between the four groups.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter Phase 1/2a, Open-Label Study of SQ3370 in Patients With Advanced Solid Tumors
Actual Study Start Date : August 1, 2020
Estimated Primary Completion Date : August 7, 2024
Estimated Study Completion Date : July 9, 2026


Arm Intervention/treatment
Experimental: Dose Escalation Cohort (10 mL SQL70)
Participants will receive 10 mL of SQL70 biopolymer injected intratumorally on Day 1 of each 21-day cycle into a single lesion and then receive escalating doses of SQP33 protodrug administered IV from Day 1 through Day 5 (5 doses) of each 21-day cycle.
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)
Participants will receive 20 mL of SQL70 biopolymer injected intratumorally on Day 1 of each 21-day cycle into a single lesion and then receive escalating doses of SQP33 protodrug administered IV from Day 1 through Day 5 (5 doses) of each 21-day cycle.
Drug: SQ3370
SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

Experimental: Cohort A
Participants will receive SQL70 biopolymer injected intratumorally on Day 1 of each 21-day cycle into a single lesion as determined in Dose Escalation. Then will receive a lower dose than RP2D of SQP33 protodrug administered IV from Day 1 through Day 5 (5 doses) of each 21-day cycle.
Drug: SQ3370
SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

Experimental: Phase 2a Expansion Group 1 (Extremity STS)
Participants with soft tissue sarcomas of the extremity AJCC Stage II, III, OR select IV (>5 cm injectable tumors by T + N1, but M0) not amendable to definitive surgical intervention at presentation and who are anthracycline naïve.
Drug: SQ3370
SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

Experimental: Phase 2a Expansion Group 2 (Unresectable STS)
Locally advanced, unresectable, 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: Phase 2a Expansion Group 3a (Head and Neck)
Participants with histologically or cytologically confirmed recurrent squamous-cell carcinoma of the head and neck, not suitable for further radical local treatment or patients with distant metastases who may have received one or less chemotherapy regimen.
Drug: SQ3370
SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin

Experimental: Phase 2a Expansion Group 3b (Ovarian/Uterine)

Participants with Epithelial ovarian cancer defined as High-grade Serious, or endometroid (grade 2/3), fallopian tube, or primary peritoneal cancer who are considered platinum refractory by the treating physician and not candidates for PARPi.

Participants with Uterine high grade carcinoma or sarcoma that is recurrent or metastatic or no longer amendable to control with surgery and or radiotherapy.

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




Primary Outcome Measures :
  1. Phase 1 Cohorts [ Time Frame: From start of treatment to approximately 12 weeks ]
    To determine the Maximum Tolerated Dose, if possible, and/or Recommended Phase 2 Dose of SQ3370

  2. Phase 2a Expansion Groups [ Time Frame: Up to 2 years ]
    To evaluate safety. Defined as type, frequency, severity, timing of onset, duration, and relationship to study drugs of any treatment-emergent adverse events (TEAEs); laboratory abnormalities; vital sign abnormalities; adverse electrocardiogram (ECG) or, ECH/MUGA findings; SAEs; or AEs leading to interruption, modification, or discontinuation of study treatment


Secondary Outcome Measures :
  1. Phase 1: Pharmacokinetics (PK) [ Time Frame: From start of treatment to approximately 12 weeks ]
    To determine Maximum Plasma concentration (Cmax) for SQP33 protodrug and active Dox following SQ3370 treatment

  2. Phase 1: Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]
    Defined as achievement of complete response (CR) or partial response (PR) by RECIST v1.1

  3. Phase 1: Duration of Response (DOR) [ Time Frame: Up to 2 years ]
    Defined as the interval from the first documentation of objective response to the earlier of the first documentation of disease progression or death from any cause

  4. Phase 2a: Objective Response Rate (ORR) [ Time Frame: Up to 2 years ]
    Defined as achievement of complete response (CR) or partial response (PR) by RECIST v1.1

  5. Phase 2a: Duration of Response (DOR) [ Time Frame: Up to 2 years ]
    Defined as the interval from the first documentation of objective response to the earlier of the first documentation of disease progression or death from any cause

  6. Phase 2a: Overall Survival [ Time Frame: Up to 2 years ]
    Defined as the time between the date of enrollment to the date of death from any cause.

  7. Phase 2a: Pharmacokinetics [ Time Frame: From start of treatment to approximately 12 weeks ]
    Determine plasma concentration and PK parameters for SQP33 protodrug and active Dox following SQ3370 treatment


Other Outcome Measures:
  1. Evaluate level of SQP33 in tumor [ Time Frame: From start of treatment to approximately 12 weeks ]
    To determine the level of SQP33 protodrug and active Doxorubicin in tumor tissue

  2. Evaluate Pharmacodynamics (PD) [ Time Frame: From start of treatment to approximately 12 weeks ]
    To assess immune response (changes in immune biomarkers) as assessed by PBMCs



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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. Subjects with un-resectable soft tissue sarcomas of the extremity AJCC Stage II, III, OR select IV (=>5 cm injectable tumors by T + N1, but M0) not amendable to primary surgical intervention according to the consensus of 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, 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

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 recurrent HNSCC or b) metastatic at initial presentation HNSCC
  2. Patients with locally advanced head and neck cancer pretreated with surgery and/or radiotherapy and not suitable for further radical local treatment
  3. Patients with distant metastases who may have received one or less chemotherapy regimen

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

  1. Metastatic or locally recurrent carcinoma of the head and neck that is considered curable by locally directed therapies
  2. Airway obstruction by tumor mass that requires clinical intervention
  3. Prior treatment with anthracyclines

Phase 2a Expansion Group 3b (Ovarian/Uterine): Inclusion

  1. Patients with Epithelial ovarian cancer defined as High-grade Serous, or endometroid (grade 2/3), fallopian tube, or primary peritoneal cancer
  2. Patients with Uterine high grade carcinoma that is recurrent or metastatic and no longer amendable to control with surgery and or radiotherapy and similarly uterine high-grade sarcomas
  3. Patients with up to three prior therapies. In patients with 1 or 2 prior treatment lines, the treatment free interval after platinum has to be less than 6 months

Phase 2a Expansion Group 3b (Ovarian/Uterine): Exclusion

  1. Non-epithelial tumor origin of the ovary, the fallopian tube or the peritoneum (i.e., germ cell tumors)
  2. Ovarian tumors of low malignant potential (e.g., borderline tumors)
  3. Prior anthracycline treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04106492


Contacts
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Contact: Shasqi Clinical Operations 415-800-1376 clinicalstudies@shasqi.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Principal Investigator    415-800-1376    clinicalstudies@shasqi.com   
Stanford Cancer Center Recruiting
Palo Alto, California, United States, 94304
Contact: Principal Investigator    415-800-1376    clinicalstudies@shasqi.com   
Sarcoma Oncology Center Recruiting
Santa Monica, California, United States, 90403
Contact: Principal Investigator    415-800-1376    clinicalstudies@shasqi.com   
United States, Missouri
Washington University in St. Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Principal Investigator    415-800-1376    clinicalstudies@shasqi.com   
United States, Oregon
Oregon Health & Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Principal Investigator    415-800-1376    clinicalstudies@shasqi.com   
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Principal Investigator    415-800-1376    clinicalstudies@shasqi.com   
Australia, New South Wales
Chris O'Brien Lifehouse Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Principal Investigator    +1 415-800-1376    clinicalstudies@shasqi.com   
Royal North Shore Hospital Recruiting
Sydney, New South Wales, Australia, 2065
Contact: Principal Investigator    +1 415-800-1376    clinicalstudies@shasqi.com   
Australia, South Australia
Cancer Research Institute Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Principal Investigator    +1 415-800-1376    clinicalstudies@shasqi.com   
Sponsors and Collaborators
Shasqi, Inc.
Investigators
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Study Director: Jim Williams, MD Shasqi, Inc.
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Responsible Party: Shasqi, Inc.
ClinicalTrials.gov Identifier: NCT04106492    
Other Study ID Numbers: SQ3370-001
2020-0185 ( Other Identifier: MD Anderson Cancer Center )
First Posted: September 27, 2019    Key Record Dates
Last Update Posted: September 21, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shasqi, Inc.:
Sarcoma
Cancer
Tumor
Soft Tissue Sarcoma
Solid Tumor
Doxorubicin
Intratumoral
Anthracycline
Phase 1
Ovarian Cancer
Precision Oncology
Precision Chemotherapy
Local Cancer Therapy
Targeted Cancer Therapy
Uterine Cancer
Head and Neck Cancer
Lung Cancer