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

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

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

Conditions
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Cancer

Intervention / Treatment
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* Drug: SQ3370


Participation Criteria
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Eligibility Criteria
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Phase 1: Inclusion Criteria: Diagnosis of advanced soft tissue sarcoma or other solid tumors Adequate hematologic, hepatic, renal, and coagulation function ECOG performance status score 0-1 Tumor is the type where published clinical data would suggest that anthracyclines have cytotoxic activity Injectable tumor present Phase 1: Exclusion Criteria: Prior exposure to 300 mg/m^2 of Dox HCl or DOXIL / CAELYX ® or 600 mg/m^2 of Epirubicin HCl Congestive heart failure (CHF), severe myocardial insufficiency, or cardiac arrhythmia 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) Trastuzumab or trastuzumab emtansine dosed within 7 months prior to Cycle 1 Day 1. Any transfusion within 14 days prior to Cycle 1 Day 1. Pregnant or breast-feeding women. 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 History of allergic reactions attributed to Dox or other anthracyclines, NaHA, hyaluronic acid, or gram-positive bacterial proteins History or evidence of clinically unstable/uncontrolled disorder, condition, or disease Phase 2a Expansion Group 1 (Extremity STS): Inclusion 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. High grade STS, Grade 2/3, with an assessable/injectable lesion of at least diameter ≥5 cm by RECIST 1.1 criteria No prior chemotherapy for STS, or radiation to affected limb Phase 2a Expansion Group 1 (Extremity STS): Exclusion Uncontrolled pain related to tumor Open wounds or tissue necrosis related to tumor mass Compartment syndrome or impending compartment syndrome Phase 2a Expansion Group 2 (Unresectable STS): Inclusion Locally advanced or metastatic, unresectable, soft-tissue sarcoma of intermediate or high grade with measurable disease. Life expectancy >12 weeks (about 3 month) Phase 2a Expansion Group 2 (Unresectable STS): Exclusion Prior exposure to anthracyclines Treatment naive extremity tumors Phase 2a Expansion Group 3a (Head and Neck): Inclusion 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 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 Airway obstruction by tumor mass that requires clinical intervention Prior treatment with anthracyclines

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional 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)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort (10 mL SQL70)<br>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<br>* SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin<br>|
| Experimental: Dose Escalation Cohort (20 mL SQL70)<br>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<br>* SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin<br>|
| Experimental: Cohort A<br>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<br>* SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin<br>|
| Experimental: Phase 2a Expansion Group 1 (Extremity STS)<br>Participants with soft tissue sarcomas of the extremity AJCC Stage III OR IV (>5 cm injectable tumors locally advanced and or metastatic, not amendable to primary surgical intervention and who are anthracycline naïve. | Drug: SQ3370<br>* SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin<br>|
| Experimental: Phase 2a Expansion Group 2 (Unresectable STS)<br>Locally advanced, unresectable or metastatic, soft tissue sarcomas who are anthracycline naïve. | Drug: SQ3370<br>* SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin<br>|
| Experimental: Phase 2a Expansion Group 3a (Head and Neck)<br>Participants with histologically or cytologically confirmed relapsed or metastatic squamous-cell carcinoma of the head and neck, who have exhausted curative intent therapies or patients with distant metastases who may have received one or less chemotherapy regimen. | Drug: SQ3370<br>* SQ3370 consists of 2 components: SQL70, a protodrug-activating biopolymer, and SQP33, a protodrug of Doxorubicin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 Cohorts | To determine the Maximum Tolerated Dose, if possible, and/or Recommended Phase 2 Dose of SQ3370 | From start of treatment to approximately 12 weeks | 
| Phase 2a Expansion Groups | 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 | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Pharmacokinetics (PK) | To determine Maximum Plasma concentration (Cmax) for SQP33 protodrug and active Dox following SQ3370 treatment | From start of treatment to approximately 12 weeks | 
| Phase 1: Objective Response Rate (ORR) | Defined as achievement of complete response (CR) or partial response (PR) by RECIST v1.1 | Up to 2 years | 
| Phase 1: Duration of Response (DOR) | 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 | Up to 2 years | 
| Phase 2a: Objective Response Rate (ORR) | Defined as achievement of complete response (CR) or partial response (PR) by RECIST v1.1 | Up to 2 years | 
| Phase 2a: Duration of Response (DOR) | 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 | Up to 2 years | 
| Phase 2a: Overall Survival | Defined as the time between the date of enrollment to the date of death from any cause. | Up to 2 years | 
| Phase 2a: Pharmacokinetics | Determine plasma concentration and PK parameters for SQP33 protodrug and active Dox following SQ3370 treatment | From start of treatment to approximately 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Uterine Cancer, 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, Head and Neck Cancer, Lung Cancer