MC# 21-11 - A Multicenter, Phase I, Open-Label Study of SQ3370 in Patients with Advanced Solid Tumors

  • Agent(s): SQ3370
  • Disease Type(s): Sarcoma, Solid Tumor
  • Phase(s): I
  • Drug Classification(s): Cytotoxic Therapy
  • Molecular Target(s): n/a

Mechanism of Action

SQ3370 consists of two drugs, SQL70 and SQP33.  SQL70 is a biopolymer that is injected into the tumor, where it remains for several weeks.  After it is injected, the attenuated protodrug SQP33 is given intravenously.  When SQP33 comes into contact with the SQL70 biopolymer, it is converted into the active cytotoxic chemotherapy drug doxorubicin.  The doxorubicin is slowly released into the tumor over a period of days and is expected to result in tumor cell death by a mechanism that includes DNA intercalation and antagonism of the enzyme topoisomerase II.

Purpose

In this study, the sponsor and investigators want to learn:

  • How much of SQP33 can be given with an acceptable level of side effects
  • The effects of SQ3370 (good and bad)
  • The safety and tolerability of SQ3370
  • How much of the SQ3370 is absorbed into the blood and how fast it is removed
Inclusion Criteria
  1. Able to provide written informed consent and understand and comply with the requirements of the study
  2. Male or female patients ≥ 18 years of age on the day of signing the Informed Consent Form (ICF)
  3. The patient is expected to have a cancer diagnosis that has been histologically or cytologically confirmed.  A confirmation is not required for each individual lesion, and it is not required for the tumor selected for injection.  In addition, the injected local or metastatic solid tumor must meet all the following criteria:
    1. is a tumor type where published clinical data would suggest responsiveness to anthracyclines (determination can be made with the Medical Monitor) and
    2. is either
      1. refractory to or relapsed following standard of care
      2. or patient ineligible for standard of care therapy
    3. and is injectable, defined as all of the following:
      1. measurable per RECIST v1.1 at baseline
      2. palpable or able to be injected percutaneously with ultrasound guidance (other modalities may be permitted based on Medical Monitor approval if the Investigator feels that the procedure is not considered of greater risk to the patient than an ultrasound-guided biopsy)
      3. not involving a vital structure or within a visceral organ
      4. accessible by repeated intratumoral or peritumoral injection with 18- to 22-gauge needle
  4. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
  5. Adequate hematologic function as defined by:
    1. absolute neutrophil count ≥ 1500 µL
    2. hemoglobin ≥ 9.0 g/dL
    3. platelet count ≥ 100,000/µL
  6. Adequate hepatic function as defined by:
    1. total bilirubin ≤ 1.2 mg/dL
    2. aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 x the upper limit of normal (ULN)
  7. Adequate renal function as defined by creatinine clearance ≥ 45 mL/min according to the Cockcroft-Gault equation
  8. Adequate coagulation function as defined by international normalized ratio ≤ 1.5 and a partial thromboplastin time ≤ 5 seconds above the ULN
  9. Women of childbearing potential and sexually active males agree to use highly effective contraception for the duration of study participation and for 90 days after the last dose of study treatment
  10. Resolution to Grade ≤ 1 AEs by the NCI-CTCAE v5.0 of all clinically significant toxic effects of prior locoregional treatment, surgery, chemoembolization, or other anticancer treatment.  Exceptions to this are Grade ≥ 1 toxicities, which, in the opinion of the Investigator and the Sponsor, are stable, and should not exclude the patient (i.e., alopecia, neuropathy, hypothyroidism, or hyperthyroidism controlled on hormone replacement therapy).
Exclusion Criteria
  1. Prior lifetime exposure to >225 mg/m2 of Dox HCl or DOXIL / CAELYX ® or 450 mg/m2 of epirubicin HCl or 135 mg/m2 Daunorubicin prior to study dosing
  2. CHF, severe myocardial insufficiency, or cardiac arrhythmia, including any one of the following:
    1. Echocardiogram (ECHO) or multigated acquisition (MUGA) scan with an actual left ventricular ejection fraction (LVEF) ≤ 45%, within 28 days prior to Cycle 1 Day 1
    2. Clinically significant cardiac arrhythmias (eg, ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (eg, bifascicular block, Mobitz type II, and third-degree AV block)
    3. Symptomatic CHF
    4. Screening QTc >470 msec and/or previous history of QT prolongation while taking other medications
    5. History or signs of active coronary artery disease with or without angina pectoris within the last 6 months
  3. Any of the following within 28 days prior to Cycle 1 Day 1:
    1. Major surgery, as defined by the Investigator
    2. Radiotherapy
    3. Chemotherapy and/or anticancer therapy.  If the agent is a small molecule kinase inhibitor, only 6 elimination half-lives is required before the patient is eligible.
    4. Currently enrolled in or discontinued from a clinical study involving an investigational product, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.  As above, if the investigational agent is a small molecule kinase inhibitor, only 6 elimination half-lives is required before the patient is eligible.
  4. Any transfusion within 14 days prior to Cycle 1 Day 1
  5. Pregnant or breast-feeding women
  6. Patients that are either positive for hepatitis B surface antigen (HBcAb) and/or detectable hepatitis B virus (HBV) DNA.  HBcAb positivity will be allowed if one or both of the following is true: a) hepatitis B surface antibody is present or b) hepatitis B DNA testing is negative and the patient is receiving hepatitis B reactivation prophylaxis with entecavir, tenofovir, telbivudine or lamivudine.
  7. Patients with hepatitis C are excluded unless they have completed a course of antiviral therapy and have undetectable levels of HCV ribonucleic acid
  8. Has a known diagnosis of immunodeficiency or is receiving either chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Day 1 Cycle 1, except in the case of central nervous system (CNS) metastases.  The use of physiologic doses of prednisone 10 mg/day or its equivalent is permitted.
  9. Patients with symptomatic concurrent conditions such as pleural effusion, ascites, or pericardial fluid requiring drainage
  10. Evidence of any active, uncontrolled bacterial, viral, parasitic or systemic fungal infections within 1 week of the first dose of study drug
  11. 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, i.e., without any of the following:
    1. Evidence of progression for at least 4 weeks by repeat imaging,
    2. Steroid treatment or stereotactic radiosurgery for at least 14 days prior to Cycle 1 Day 1,
    3. Whole brain radiation therapy for at least 28 days prior to Cycle 1 Day 1
  12. Known or active other malignancies that have needed treatment (excluding palliative radiation) within 2 years prior to Cycle 1 Day 1 are excluded except for the following:
    1. Curatively resected nonmelanomatous skin cancer,
    2. Curatively treated cervical carcinoma in situ,
    3. Non-metastatic breast and prostate cancer patients with stable disease > 12 months,
    4. Other stable malignancies may be permitted based on Medical Monitor approval
  13. Elective or a planned major surgery to be performed during the study
  14. History of allergic reactions attributed to Dox or other anthracyclines
  15. History of allergic reactions attributed to NaHA, hyaluronic acid, or gram-positive bacterial proteins
  16. Patients who have received a live vaccine, including live SARS-CoV-2/COVID-19 vaccines, within 28 days of Cycle 1 Day 1.  Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (eg, Flu-Mist®) are live attenuated vaccines and are not allowed.
  17. History or evidence of a clinically unstable/uncontrolled disorder, condition or disease (including but not limited to cardiopulmonary, renal, metabolic, hematologic or neurologic) other than their primary malignancy, that in the opinion of the Investigator would pose a risk to patient safety or interfere with the study evaluation, procedures or completion

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT04106492

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Re: MC# 21-11