A Phase 1, Open-label, First-in Human Study to Examine the Safety, Tolerability, Pharmacokinetic Profile, and Preliminary Efficacy of OZ-001 when Administered Orally in Adults with Solid Tumours with a Focus on Triple Negative Breast Cancer (Phase 1a)

Exclusion Criteria32

• Any major surgery or any therapy within the last 4 weeks and/or not recovered from prior therapy/surgery.
• Receiving anticancer therapy (chemotherapy, surgery, or radiotherapy, etc.) within 28 days of OZ-001 administration. (Note that patients receiving localized palliative radiation can be allowed on the study after discussion with the Sponsor).
• Patients with unresolved toxicities from prior anticancer therapies not resolved to baseline or Grade 1. Patients with residual AEs >Grade 1 considered NCS may be allowed on a case-by-case basis after consultation with the Sponsor.
• Confirmed brain metastases, with the exception of stable brain metastases defined as:
• a. The patient’s brain metastases have been treated or do not require urgent local treatment at the time of study enrolment or are unlikely to require treatment during the study.
• b. The patient has been off dexamethasone or is on a stable dose of dexamethasone of less than or equal to 2 mg daily (or an alternate steroid equivalent) for at least 2 weeks prior to first OZ-001 administration.
• c. Patients are stable (no evidence of progression or new enlarging brain metastases) by imaging; same imaging modality (magnetic resonance imaging [MRI] or computed tomography [CT] scan must be used for each assessment) for at least 28 days prior to the first dose of OZ-001.
• Note: Patients with a history of carcinomatous meningitis may not participate even if stable clinically.
• Liver cirrhosis, a history of or positive test results for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit. Patients positive for HCV antibody, negative for viral load by polymerase chain reaction (PCR) and treated may be eligible after discussion with Sponsor.
• Clinically significant interstitial pulmonary disease.
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death), a known arrythmia, or receiving drugs that prolong the QTc interval.
• Evidence of abnormal cardiac function, as defined by the following:
• a. Presence of New York Heart Association Class III or IV congestive heart failure;
• b. Hypertension that cannot be controlled by medications (>160/100 mmHg despite optimal medical therapy);
• c. Presence of myocardial infarction in the previous 6 months;
• d. Presence of clinically significant bradycardia, or other uncontrolled cardiac arrhythmia defined as Grade 3 or 4 according to NCI-CTCAE Version 5.0 unless the patient has a pacemaker;
• e. Prolongation of HR corrected QT interval by Fridericia’s method (QTcF) at rest, where the mean QTcF interval is >470 ms based on ECG. If QTcF exceeds 470 ms the ECG should be repeated 2 more times and the average of the 3 QTcF values should be used to determine the patient’s eligibility.
• Acute or subacute intestinal obstruction or inflammatory bowel disease within 6 months of study enrolment.
• Participation in another clinical study of an investigational drug or investigational device within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to screening.
• Known hypersensitivity to any of the OZ-001 ingredients.
• History of anaphylaxis or other significant allergy which, in the opinion of the PI (or delegate), would interfere with the volunteer’s ability to participate in the study.
• History of second primary malignancy within 3 years prior to starting study treatment (excluding completely resected cervical cancer or surgically resected skin squamous cell or basal cell carcinoma).
• Major psychiatric disorder and/or history of suicide ideation. Any other psychiatric illness that, in the opinion of the PI (or delegate), may affect compliance with scheduled visits.
• Female who is pregnant or breastfeeding, or who plans to become pregnant and/or breastfeed.
• Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
• History of known alcohol or substance abuse and/or a known psychiatric illness/social situation that would limit compliance with study requirements.
• Use of live vaccinations within 30 days prior to screening.
• Any thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events); within 6 months.
• Any medications or food that interact with cytochromes or receiving medications that are strong inhibitors or inducers of cytochrome P450 (CYP)3A4 including grapefruit, grapefruit juice, bitter orange [Seville orange], pomegranate, or star fruit.
• Patients must not be using immunosuppressive medication >10 mg prednisolone per day or equivalent within 14 days prior to the first dose of the OZ-001, with the exception of local (topical, nasal, or inhaled) steroid use.
• Note: Use of immunosuppressive medications as prophylaxis in patients with contrast allergies is acceptable.
• Any other condition, medical illness, or prior therapy that in the opinion of the PI (or delegate) would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements.