A Phase 2, Open Label Study of PEmigatinib and REtifanlimab in Advanced Dedifferentiated LIposarcoma
Dedifferentiated liposarcomas (DDLPS) are aggressive soft tissue sarcomas with no effective medical treatment options. Immunotherapy with checkpoint inhibitors, so-called PD-1 inhibitors, have shown some effect in DDLPS in previous studies. Effect of immunotherapy can be improved by combining it with other types of tumor drugs. Medicines that inhibit signaling via the FGF receptor, so-called FGFR inhibitors, have shown a tumor-slowing effect in DDLPS in early studies. FGFR inhibitors can also induce changes that make the tumor more available to treatment with immunotherapy. The study aims to investigate whether the combination of an FGFR inhibitor, pemigatinib, with a PD-1 inhibitor, retifanlimab can provide a tumor-slowing effect in patients with advanced DDLPS who have progressed on first-line treatment.
‣ Participants will be eligible for the study if all of the following criteria are met:
• Be 18 years of age or above, on day of signing informed consent.
• Must be willing and able to provide written informed consent. Written informed consent must be signed and dated before the start of specific protocol procedures.
• Must be willing and able to conform to and comply with all protocol requirements, including, all scheduled visits, protocol procedures, and the ability to swallow oral tablets.
• 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.
• Disease relapse or radiological progression, as determined by the Investigator, within the last 6 months after at least one line of systemic treatment.
• a. Patients considered to be medically unfit for chemotherapy, as assessed by the sarcoma centre in charge of the patient's treatment, can be considered for the trial after discussion with the trial steering committee.
• 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.
• Patient must have adequate organ function as indicated by laboratory values obtained within 14 days of receiving the first dose of study drug (see study protocol)
⁃ Female patients of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
⁃ Female patients of childbearing potential must be willing to use a highly effective method of contraception, for the course of the study through 180 days after the last dose of study medication. Please refer to Section 5.3 for list of highly effective contraception.
⁃ Male patients must agree to use an highly effective method of contraception starting with the first dose of study therapy through 180 days after the last dose of study therapy.