PERELI - A phase 2, open label study of PEmigatinib and REtifanlimab in advanced dedifferentiated Liposarcoma

Trial ID: 2022-501993-21-00
Protocol: PERELI
Sponsor: Region Skane

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Diseases & Conditions

Liposarcoma Dedifferentiated liposarcoma Liposarcoma metastatic

Objectives

The primary objective of this study is to evaluate the **clinical benefit** of retifanlimab and pemigatinib in patients with advanced dedifferentiated liposarcoma (DDLPS). This is clinically relevant as DDLPS is a challenging malignancy with limited treatment options, and assessing the efficacy of these agents could potentially lead to improved therapeutic strategies.

Secondary objectives include:

Further evaluation of the clinical efficacy of retifanlimab and pemigatinib in DDLPS.
Assessment of the safety and tolerability of pemigatinib and retifanlimab.
Evaluation of the impact of treatment and disease status on quality of life.
Examination of the relationship between baseline and on-treatment biomarkers and clinical activity.

Participants

The clinical trial involves participants diagnosed with **dedifferentiated liposarcoma** (DDLPS), a rare type of cancer. The study population includes both male and female subjects, aged 18 years and older, who are considered part of a vulnerable population. Participants are required to have a histologically confirmed diagnosis of DDLPS, with evidence of MDM2 amplification or positive MDM2 immunohistochemistry. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants must have at least one measurable lesion that is not amenable to surgery or other curative treatments. The trial population was selected based on specific inclusion criteria, including a performance status of 0-2 on the ECOG Performance Scale. Lifestyle considerations such as diet, physical activity, or habits are not detailed in the available data.

Plans and Procedures

The clinical trial is designed to evaluate the **clinical benefit** of retifanlimab and pemigatinib in patients with advanced dedifferentiated liposarcoma. This is a phase II, open-label study, which means that both the researchers and participants know which treatment is being administered. The trial is expected to commence on October 1, 2023, and conclude by April 1, 2027. Participants will be involved in the study for a maximum treatment period of 42 days, with the possibility of early termination if disease progression or unacceptable toxicity occurs.

The trial will include several study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, histological confirmation of dedifferentiated liposarcoma, and performance status. Participants must be 18 years or older and have at least one measurable lesion that is not amenable to surgery or other curative treatments. Following the screening, participants will undergo regular follow-up visits to monitor treatment response and adverse events. The primary endpoint is progression-free survival at 24 weeks, with secondary endpoints including objective response rate, overall survival, and changes in quality of life.

Participants will receive retifanlimab via **intravenous infusion** and pemigatinib orally. The study will assess the incidence and severity of adverse events, with all changes in laboratory values, vital signs, and physical examinations graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. The end-of-study visit will occur after the treatment period to evaluate the overall outcomes and any long-term effects. The trial's design ensures a comprehensive assessment of the therapeutic potential of the investigational products in this patient population.

Treatment

The clinical trial involves the administration of **Retifanlimab** (INCMGA00012), a **solution for infusion**. This experimental medication is a protein of biological/biotechnological origin, specifically designed for intravenous infusion. The maximum daily dose of Retifanlimab is 375 mg, with a total maximum dose of 23,000 mg over a treatment period of 42 days. The administration schedule is determined by the study protocol, and participant compliance is monitored throughout the trial to ensure adherence to the dosing regimen. Retifanlimab is provided by Incyte Corporation and is designated as an orphan drug for this study.

In addition to Retifanlimab, the trial also includes the administration of **Pemazyre** 4.5 mg tablets, containing the active substance **Pemigatinib**. This medication is of chemical origin and is administered orally. The maximum daily dose for Pemigatinib is 13.5 mg, with a total maximum dose of 16,868 mg over the same 42-day treatment period. Pemazyre is supplied by Incyte Biosciences Distribution B.V. and is also designated as an orphan drug. The dosing schedule for Pemigatinib is outlined in the study protocol, and participant compliance is closely monitored to ensure proper administration.

Both Retifanlimab and Pemigatinib are used in this study to evaluate their clinical benefit in patients with advanced dedifferentiated liposarcoma. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The study is designed to assess the efficacy and safety of these investigational drugs in the specified patient population.

Efficacy

Efficacy in the clinical trial titled "PERELI - A phase 2, open label study of PEmigatinib and REtifanlimab in advanced dedifferentiated Liposarcoma" will be assessed using several primary and secondary endpoints. The primary endpoint is **Progression-free survival (PFS)** at 24 weeks, defined as the time from the first dosing date to the date of the first objectively documented disease progression or death due to any cause, based on tumor assessment using RECIST version 1.1 criteria.

Secondary endpoints include the Objective Response Rate (ORR), which is the percentage of patients achieving a confirmed complete or partial response as defined by RECIST v1.1. Overall Survival (OS) will be calculated from the start of treatment to the date of death from any cause. The Best Overall Response (BOR) will be recorded according to RECIST v1.1, and Time to Response (TTR) will be calculated from the start of treatment to the first documented complete or partial response. Duration of Response (DOR) will be measured from the first documented response to progression or death due to underlying cancer.

Additional assessments include the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5. Changes in patient performance status from baseline will be evaluated using the Eastern Cooperative Oncology Group (ECOG) Performance Scale at 24 weeks. Quality of life changes from baseline will be assessed using the EORTC QLQ-C30 questionnaire.

Inclusion and Exclusion Criteria

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Inclusion Criteria

● Be 18 years of age or above, on day of signing informed consent
● Histologically confirmed DDLPS*. Written pathology report indicating the diagnosis of DDLPS with positive MDM2 immunohistochemistry or MDM2 amplification as demonstrated by fluorescence in situ hybridization, polymerase chain reaction (PCR) or sequencing-based methods must be available.
● Have the presence of at least 1 measurable lesion by CT per RECIST v1.1 that is considered non amenable to surgery or other curative treatments or procedures. Tumor lesions located in a previously irradiated area or in an area subjected to other loco-regional therapy are considered measurable if progression has been demonstrated in the lesion.
● Be willing to provide tissue by core or excisional biopsy of a tumor lesion at the time points specified in the Trial Flow Chart. Archival tumor tissue can be used instead of pre-treatment biopsy. Biopsy will only be performed if the risk of complication is considered acceptable for the patient.
● Have a performance status of 0-2 on the ECOG Performance Scale.

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Exclusion Criteria

● Receipt of anticancer therapy within 28 days of the first administration of study treatment, with the exception of localized radiotherapy.
● Toxicity of prior therapy that has not recovered to ≤ Grade 1 (with the exception of alopecia, peripheral neuropathy and anemia not requiring transfusional support), unless approved by the trial steering committee
● Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
● Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
● Hypersensitivity to pemigatinib or retifanlimab or any of its excipients.
● Has known active central nervous system (CNS) metastases and/or sarcomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include sarcomatous meningitis which is excluded regardless of clinical stability.
● Has an active autoimmune disease requiring systemic immunosuppression with corticosteroids (> 10 mg/day of prednisone or equivalent) or immunosuppressive drugs within 14 days before the first dose of study treatment.
● Has an active infection requiring systemic antibiotics or antifungal or antiviral treatment within 7 days before first dose of study treatment.
● Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
● Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
● Has received prior therapy with a selective FGFR inhibitor.
● Has received a live vaccine within 30 days of planned start of study therapy.
Has a history of calcium or phosphate homeostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues such as the skin, kidney tendon, or vessels due to injury, disease, or aging in the absence of systemic mineral imbalance).
Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is shorter) before the first dose of study drug.
Has a history of hypovitaminosis D currently requiring supraphysiologic doses (eg, 50,000 UI/weekly) to replenish the deficiency. Vitamin D supplements are allowed.