INCB 50465-801: A Phase 2, Open-Label, Multicenter, Rollover Study to Provide Continued Treatment for Participants Previously Enrolled in Studies of Parsaclisib (INCB050465)

The primary objective of this Phase 2, open-label, multicenter rollover study is to provide continued treatment and evaluate the safety of **parsaclisib** (INCB050465) in participants with advanced malignancies and immune-mediated inflammatory diseases. This study involves the administration of parsaclisib as monotherapy or in combination with other agents such as itacitinib (INCB039110), ruxolitinib (INCB018424), ibrutinib, or tafasitamab (INCMOR00208), including participants who remain on tafasitamab alone. The clinical relevance of this objective lies in ensuring the ongoing safety and therapeutic benefit of parsaclisib for patients who have previously participated in related studies, thereby facilitating the management of their conditions with a potentially effective treatment regimen.

The clinical trial involves a total of **56 participants** diagnosed with **advanced malignancies** and immune-mediated inflammatory diseases (IAI). The study population includes both male and female subjects, with an age range that spans from young adults to older adults. Participants were selected based on their current enrollment and treatment in an Incyte-sponsored clinical study of parsaclisib, ensuring they are tolerating and benefiting from the treatment. The trial includes individuals who are part of a vulnerable population, indicating a need for careful monitoring and ethical considerations. Participants are required to comply with scheduled visits and treatment plans, including prophylaxis for Pneumocystis jirovecii pneumonia (PJP), and must demonstrate compliance with the parent protocol requirements. The study does not specify particular lifestyle considerations such as diet or physical activity, focusing instead on the medical and treatment-related criteria for inclusion.

The clinical trial is designed as a **Phase 2**, open-label, multicenter, rollover study aimed at providing continued treatment and evaluating the safety of **parsaclisib** as monotherapy or in combination with other agents such as **itacitinib**, **ruxolitinib**, **ibrutinib**, or **tafasitamab**. The trial targets participants with advanced malignancies and inflammatory and autoimmune diseases (IAI) who are currently enrolled in an Incyte-sponsored study of parsaclisib and are experiencing clinical benefits from the treatment. The study is not categorized as low intervention and is expected to conclude by September 30, 2024.

The trial follows a structured sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as current enrollment in a parent protocol, treatment tolerance, and compliance with protocol requirements. Participants must demonstrate at least stable disease and willingness to comply with study procedures, including prophylaxis for Pneumocystis jirovecii pneumonia (PJP). Follow-up visits are scheduled to monitor safety and efficacy, with the primary endpoint being the assessment of adverse events (AEs) and serious adverse events (SAEs) in participants receiving parsaclisib. The end-of-study visit will mark the conclusion of the participant's involvement, unless early termination is warranted due to non-compliance, adverse reactions, or withdrawal of consent.

Participant involvement is expected to last up to 23 months, depending on individual treatment response and adherence to the study protocol. Conditions that may lead to early termination include significant adverse events, lack of compliance with the treatment regimen, or the investigator's decision based on the participant's best interest. The trial's design ensures rigorous monitoring and evaluation to maintain participant safety and data integrity throughout the study duration.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. The primary experimental medication is **Parsaclisib (INCB050465)**, which is provided in tablet form. The active substance is **parsaclisib hydrochloride**, a chemical compound. The maximum daily dose is 20 mg, with a total maximum dose of 13,990 mg over a treatment period of up to 23 weeks. The medication is administered orally.

Another treatment used in the trial is **IMBRUVICA 140 mg hard capsules**, containing the active substance **ibrutinib**. This medication is also a chemical compound and is administered orally. The maximum daily dose is 560 mg, with a total maximum dose of 560 mg over a treatment period of up to 22 weeks.

**Jakavi 5 mg tablets** are included as a non-experimental treatment, containing the active substance **ruxolitinib**. This chemical compound is administered orally, with a maximum daily dose of 50 mg and a total maximum dose of 34,980 mg over a treatment period of up to 23 weeks.

Additionally, **MINJUVI 200 mg powder for concentrate for solution for infusion** is used, containing the active substance **tafasitamab**. This protein-based compound is administered via intravenous infusion. The maximum daily dose is 12 mg/kg, with a total maximum dose of 552 mg/kg over a treatment period of up to 23 weeks.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed treatment regimens. The trial aims to evaluate the safety and continued treatment efficacy of these medications, either as monotherapy or in combination with other treatments. The trial does not include any placebo or comparator treatments, focusing solely on the aforementioned medications.

The efficacy of the clinical trial will be assessed by evaluating the occurrence of adverse events (AEs) and serious adverse events (SAEs) in participants receiving **parsaclisib** as monotherapy or in combination with other treatments such as itacitinib, ruxolitinib, ibrutinib, or tafasitamab. This assessment will focus on participants who continue to receive tafasitamab alone as well. The primary endpoint is to monitor and document these AEs and SAEs throughout the trial duration. The trial is designed as a Phase 2, open-label, multicenter rollover study, aiming to provide continued treatment and evaluate safety in participants previously enrolled in studies of **parsaclisib**. The trial will not include secondary endpoints for efficacy assessment. The study will ensure that participants are monitored for compliance with the treatment protocol and any other study procedures as indicated. The trial is expected to conclude by September 30, 2024.