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Lay Description

This study is an open-label, multi-center, dose-escalation study in adult subjects with advanced solid tumors for whom standard therapy is not available for their stage of disease. The study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics (preliminary anti-tumor activity and gene expression analysis) of SM08502 administered orally, once daily, for 28 consecutive days. Dosing in 28-day cycles will continue within each subject, unless treatment is discontinued due to toxicity, disease progression, initiation of a new anti-neoplastic therapy, withdrawal of consent, the Sponsor terminates the study, or the subject no longer meets retreatment criteria.

Category

  • Cancers and Other Neoplasms
IRB Number
20210264HU
NCT Number
ct.gov registration not required
Open to Enrollment
Yes

Eligibility

Eligible Ages
18
Eligible Genders
ANY
Accepts Healthy Volunteers

Inclusion Criteria

  1. Subjects with advanced solid tumors (as defined below):

Part 1A [WRC1] – Subjects with advanced solid tumors who are refractory to or intolerant of established therapy known to provide clinical benefit for their condition (i.e., subjects must not be candidates for regimens known to provide clinical benefit) and for which histologic or cytologic confirmation of malignancy was obtained at diagnosis, with the exception of hepatocellular carcinoma if it meets appropriate imaging-only diagnostic criteria [per the National Comprehensive Cancer Network (NCCN), Liver Imaging Reporting and Data System (LI-RADS), American Association for the Study of Liver Diseases (AASLD), Asian Pacific Association for the Study of the Liver (APASL), or European Association for the Study of the Liver – European Organisation for Research and Treatment of Cancer (EASL-EORTC)].

    1. Part 1B – Subjects with advanced and/or metastatic solid tumors who are refractory to or intolerant of established therapy known to provide clinical benefit for their condition (i.e., subjects must not be candidates for regimens known to provide clinical benefit in the Investigator’s judgement). Histologic or cytologic confirmation of malignancy must have been obtained at diagnosis. The enrichment indications eligible for Part 1B are those that are thought to have the highest likelihood of response based on the mechanism of action of SM08502 and include:
      1. NSCLC (adenocarcinoma subtype)
      2. TNBC
      3. CRPC
      4. CRC
      5. Endometrial cancer (endometrioid subtype)
      6. Ovarian cancer (serous, mucinous, and endometrioid subtypes)
    2. Part 2 – Subjects with advanced and/or metastatic solid tumors who are refractory to or intolerant of established therapy known to provide clinical benefit for their condition. Histologic or cytologic confirmation of malignancy must have been obtained at diagnosis. Subjects must have received at least two lines of prior therapy. The enrichment indications eligible for Part 2 are those that are thought to have the highest likelihood of response based on the mechanism of action of SM08502 and include:
      1. NSCLC (adenocarcinoma subtype)
      2. TNBC
      3. CRPC
      4. CRC
      5. Endometrial cancer (endometrioid subtype)
      6. Ovarian cancer (serous, mucinous, and endometrioid subtypes)
  1. Male or female subjects ≥ 18 years of age
  2. Measurable or evaluable disease per RECIST 1.1 (Part 1A). For Parts 1B and 2, at least one measurable lesion per RECIST 1.1 that has not been previously irradiated. In CRPC subjects (Parts 1B and 2) without measurable disease per RECIST 1.1, a PSA that is concordant with clinical disease progression (rising) is eligible. A PSA value of 2 ng/ml or greater is required for study entry.
  3. Subjects must have archived tumor specimens available for analysis. Otherwise, a fresh tumor biopsy will be required at study entry. At the discretion of the Sponsor’s Medical Monitor, a fresh tumor biopsy may not be required for CRPC subjects with bone-only disease who have unavailable or insufficient archived tumor specimens.
  4. A portion of the subjects in the CRC, TNBC, and NSCLC cohorts of Part 2 will be required to provide a pre-treatment and post-treatment biopsy.
  5. Subjects must have recovered (i.e., Grade 1 [or better] based on CTCAE v5.0) from all toxicity associated with previous chemotherapy, targeted therapy, experimental therapy, biological therapy, immuno-oncology therapy, surgery, radiotherapy, or other locoregional therapy (Exceptions include subjects with: continuing alopecia regardless of any CTCAE grade, Grade 2 or lower neuropathy, and well-controlled hypothyroidism and/or adrenal insufficiency on chronic hormone replacement. All subjects with these exceptions are eligible.) The following intervals must elapse between end of last treatment and receiving the first dose of SM08502:
    1. Chemotherapy: 3 weeks
    2. Mitomycin C or a nitrosourea: 6 weeks
    3. Radiotherapy: 3 weeks
    4. Major surgery: 6 weeks
    5. Targeted therapy, including monoclonal antibodies and immuno-oncology therapies: 4 weeks or 5 half-lives, whichever is shortest
    6. Anti-hormonal therapy: 3 weeks. The exception is ADT (such as goserelin or leuprolide) for subjects with CRPC who are progressing on therapy, ADT may be continued in this study.
    7. Experimental therapy: 4 weeks or 5 half-lives, whichever is shortest
    8. Other locoregional therapy [e.g., radiofrequency ablation (RFA), TACE (transarterial chemoembolization), TARE (transarterial radioembolization), DEB-TACE (drug eluting bead transarterial chemoembolization)]: 6 weeks
  6. Subjects must meet the following laboratory criteria at Screening for study entry:
    1. Hepatic function: serum total bilirubin ≤ 1.5x upper limit of normal (ULN), AST/ALT ≤ 2.5x ULN. For subjects with Gilbert’s syndrome, serum total bilirubin

≤ 3x ULN

    1. Renal function: measured or calculated creatinine clearance via Cockcroft-Gault formula >35 mL/min
    2. Hematology: absolute neutrophil counts ≥ 1500/mm3, platelet counts ≥ 100,000/mm3, hemoglobin ≥ 9.0 g/dL

Subjects with values within 10% of these limits deemed not clinically significant by the Investigator may be entered with the approval of the Sponsor’s Medical Monitor.

  1. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  2. Life expectancy > 3 months
  3. Subjects must have no uncontrolled intercurrent illness
  4. Subjects must have the ability to swallow and retain oral medication
  5. Subjects must be willing to avoid extensive sun exposure, phototherapy, and use of a tanning salon during trial participation.
  6. Subjects must be willing to sign and provide informed consent and be capable of giving informed consent in accordance with the Institutional Review Board (IRB)/Ethics Committee (EC) policy
  7. Willingness to comply with all scheduled study visits, laboratory tests, contraception requirements, and other study procedures

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Exclusion Criteria

  1. Women who are pregnant or lactating
  2. Women of childbearing potential (WOCBP) who do not agree to follow the contraceptive guidelines
  3. Men of reproductive potential who do not agree to follow the contraceptive guidelines as outlined
  4. Subjects with a corrected QT interval (QTc) using Fridericia’s formula (QTcF) > CTCAE v5.0 Grade 1 (>480 msec) based on the mean of triplicate evaluation at Screening. In subjects with ventricular paced rhythm, a 50 msec subtraction should be applied to the QTc to calculate the QTcF, potential exceptions for subjects with pacemakers should be discussed with the Sponsor’s Medical Monitor
  5. Subjects with clinically significant ventricular tachycardia (VT), atrial fibrillation (AF), ventricular fibrillation (VF), second or third degree heart block
  6. Subjects with myocardial infarction (MI) within 1 year, Class II-IV congestive heart failure (CHF) per New York Heart Association (NYHA) classification, or clinically significant coronary artery disease (CAD)
  7. Subjects currently using or anticipating the need for food or drugs known to strongly inhibit or induce CYP3A4, such as ketoconazole, itraconazole, erythromycin, or rifampin, within 10 days prior to first dose of study medication
  8. Subjects with active infection requiring parenteral antibiotic therapy
  9. Organ transplant recipients
  10. Subjects with untreated, progressing, or known symptomatic brain metastasis. Asymptomatic subjects whose brain metastasis have been adequately treated and have remained stable for ≥ 1 month after completion of treatment (based on screening MRI of the brain compared to prior evaluations) and have discontinued corticosteroid treatment are eligible.
  11. Subjects with known osteoporosis
  12. Subjects with a second malignancy unless adequately treated with no recurrence for 3 years. Subjects with a history of previous or recent adequately treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of any source are eligible.
  13. Subjects with known hypersensitivity to any excipients in the study drug formulation
  14. Subjects with active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of SM08502 per Investigator’s opinion
  15. Subjects with known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection
  16. Subjects considered by the Investigator to be unsuitable for the study for any other reason
  17. Subjects with retinal abnormalities, specifically diabetic retinopathy, macular degeneration, other forms of retinal degenerative disease, or other retinal findings that may place the subject at risk (the latter should be discussed with the Medical Monitor).
  18. Subjects with chronic liver disease or dysfunction and a Child-Pugh score of B or C
  19. Subjects who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of personnel directly affiliated with the study at any investigative site, or are directly affiliated with the study at any investigative site
  20. Subjects employed by Biosplice, or any of its affiliates or development partners (that is, an employee, temporary contract worker, or designee) responsible for the conduct of the study, or who are immediate family members (spouse, parent, child, or sibling; biological or legally adopted) of said employees responsible for the conduct of the study

Study Design

Arm Groups

Study Contact


Regulatory Point of Contact
Frances Crawford
(210) 450-5037
crawfordf1@uthscsa.edu

Regulatory Point of Contact
Sonia Creighton
(210) 450-1366
creighton@uthscsa.edu

Regulatory Point of Contact
Karla Hagerty
(210) 450-1000
hagertyk@uthscsa.edu

Regulatory Point of Contact
Myrna Montenegro
(210) 450-5954
montenegro@uthscsa.edu

Regulatory Point of Contact
Mailbox Ctrc Regulatory Affairs
regaffapp@uthscsa.edu

Regulatory Point of Contact
Kathleen Rodriguez
(210) 450-1365
rodriguezk3@uthscsa.edu

Regulatory Point of Contact
Benjamin Schleif
(210) 450-1366
schleifb@uthscsa.edu

Regulatory Point of Contact
Morgan Seekatz
(210) 450-1133
seekatz@uthscsa.edu

Principal Investigator
Daruka Mahadevan