A Study of Roginolisib in Combination With Ruxolitinib in Patients With Myelofibrosis (MF) Who Are Unresponsive to JAK Inhibitors

Exclusion criteria

• . Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications.
• . History of a prior Grade 3 or 4 AE which did not respond to therapy or resolved with treatment interruptions and returned to at least Grade 1, other than fatigue. Note: Patients with ≤ Grade 2 neuropathy or alopecia are an exception and may enrol.
• . Active autoimmune process (e.g., rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease, immune colitis) for which systemic treatment (i.e., use of disease-modifying agents, corticosteroids, or immunosuppressive drugs) is required. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• . History or presence of an abnormal ECG that, in the Investigator's opinion, is clinically meaningful. Screening QTc interval \> 480 milliseconds is excluded (corrected by Fridericia). In the event that a single QTc is \> 480 milliseconds, the patient may enrol if the average QTc for the 3 ECGs is \< 480 milliseconds. For patients with an intraventricular conduction delay (QRS interval \> 120 msec), the JTc interval may be used in place of the QTc with Sponsor approval. The JTc must be \< 340 milliseconds if JTc is used in place of the QTc. Patients with left bundle branch block are excluded.
• . Clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrolment), myocardial infarction (\< 6 months prior to enrolment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• . Patients with active malignancy requiring concurrent intervention or previous malignancies unless a complete remission was achieved at least 2 years prior to study entry and no additional therapy is required during the study period and the patient is assessed at low risk of relapse by the investigator. Note: Patients with a slow progressing cancer (e.g. prostate) or an in situ cancers (e.g. cervical dysplasia) are permitted.
• . Any serious or uncontrolled medical disorder or active infection that, in the opinion of the Investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the patient to receive protocol therapy.
• . Use of the following treatments within the time periods noted: