IRB Study Number 24-650
Status Recruiting
Phase Phase 1
Institute Taussig Cancer Institute
Description
3.1 Primary Objectives
To assess the safety and tolerability of SA53-OS administered as monotherapy.
To establish the MTD and candidate RP2D of SA53-OS.
3.2 Secondary Objectives
To describe the pharmacokinetic (PK) profile of SA53-OS.
To describe any preliminary efficacy of SA53-OS in patients with DD LPS and other p53 wild-type solid tumors.
3.3 Exploratory Objective
- To explore potential biomarkers of sensitivity, resistance, and toxicity for SA53-OS.
Inclusion Criteria
- Tumor characteristics of participants in Phase 1
a. Histologically and/or cytologically confirmed diagnosis of advanced or metastatic solid tumor and/or non-Hodgkin lymphoma excluding primary central nervous system malignancy for which no standard effective treatment exists or where that treatment was declined (reason is to be recorded in the case report form [CRF]). Participants with non-Hodgkin lymphoma should have failed ≥ 2 prior lines of systemic therapy prior enrollment.
b. Tumor p53 wild-type.
c. Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) is NOT REQUIRED for all participants in Phase 1 (see Appendix A).
- Tumor characteristics of participants in Phase 2a
a. Cohort A: Tumor p53 wild-type with histologically confirmed diagnosis of advanced or metastatic DD LPS (and MDM2 amplification). OR
Cohort B: Tumor p53 wild-type in other solid tumor.
b. Measurable disease by RECIST 1.1 (see Appendix A).
18 years old or older.
Available archival tissue (formalin-fixed paraffin-embedded tumor block or slides).
Resolution of clinically relevant toxicity-related to prior anticancer therapies prior to receipt of study treatment to Grade 1 or less.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (see Appendix B).
Adequate organ function defined as:
a. White blood cells ≥ 2000/μL
b. Absolute neutrophil count ≥ 1500/μL
c. Platelets ≥ 100 x109/L (without transfusion within 2 weeks)
d. Hemoglobin ≥ 9 g/dL (without red blood cell transfusion within 2 weeks of initiation of study treatment)
e. Calculated creatinine clearance ≥ 60 mL/min per the Cockcroft and Gault formula (see Appendix C)
f. AST ≤ 2.5 × upper limit of normal (ULN)
g. ALT ≤ 2.5 × ULN
h. Total bilirubin ≤ 1.5 × ULN (except patients with Gilbert’s syndrome, who must have a total bilirubin ≤ 3.0 mg/dL)
i. International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
Participants of childbearing/reproductive potential must agree to use adequate birth control measures (refer to Section 8.1.1) during the course of the trial and for at least 3 months after discontinuing study treatment.
Able and willing to provide informed consent.
Exclusion Criteria
Any condition that could affect the absorption of the study drug, in the opinion of the Investigator.
Anticancer treatment (chemotherapy, radiotherapy, biotherapy, or investigational agents) within 2 weeks prior to start of study treatment. Prior focal radiotherapy within 2 weeks.
Major surgery within 2 weeks prior to the first dose of study treatment.
Anticipated need for major surgery and/or localized palliative radiation within the next 6 weeks
Active, untreated central nervous system metastases. Patients with brain metastases identified at Screening may be rescreened after the lesion(s) have been appropriately treated; patients with treated brain metastases should be neurologically stable for 4 weeks post-treatment and prior to study enrollment, and off corticosteroids for at least 2 weeks before start of study treatment, and treated lesions should demonstrate no new growth on the re-screening scan.
Known HIV infection or active hepatitis B or C infection.
Thrombotic event requiring active and ongoing anticoagulation within the last 6 months prior to study treatment.
Myocardial infarction within the last 6 months prior to study treatment.
Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, congestive heart failure New York Heart Association (NYHA) Class III or IV related to primary cardiac disease, uncontrolled ischemic or severe vascular heart disease.
QTcF (corrected QT using Friderica) > 450 milliseconds (ms).
Use of any medications known to prolong the QT/QTc interval during the study.
Concomitant use of proton pump inhibitors and H2 blockers during study treatment (24 hours before and on dosing days). Antiacids should not be used within 2 hours before and 2 hours after dosing.
A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
Known bleeding disorder (e.g., hemophilia, von Willebrand disease).
Conditions that may predispose to major bleeding (e.g., active GI ulcers, upper or lower GI bleedings in the last 6 months, significant hemoptysis in the last 6 months, tumor invasion of major vessels, etc.). Conditions that have been treated may be allowed if resolution of the risk is documented.
Use or indication for full dose anticoagulation or anti-platelet therapy including low dose aspirin. Low dose anticoagulation, as for catheter or port patency is permitted.
Use of any non-steroidal anti-inflammatory drugs (NSAIDs) if platelet count is ≤100K. Low, intermittent doses of NSAIDs are permitted if platelet count is >100K.
Live-attenuated vaccine therapy within 4 weeks prior to first dose of study treatment.
Use of any prophylactic growth factors.
Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the judgment of the Investigator, would make the patient inappropriate for entry into the trial.
Women who are pregnant or lactating. All female patients with reproductive potential must have a negative serum pregnancy test prior to starting treatment.
Unable or unwilling to comply with study requirements, including returning for follow-up visits.
