A Phase 2, Open Label Study of PEmigatinib and REtifanlimab in Advanced Dedifferentiated LIposarcoma (PERELI)

NCT06389799 | Recruiting Phase 2 DMC

• 2 other identifiers: PERELI2022-501993-21-00
• Study Type: interventional
• Target: 33
• Locations: 2 countries
• Sites: 4

Brief Summary

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.

Conditions

Dedifferentiated Liposarcoma

Outcome Measures

Primary Outcomes (1)

• To evaluate clinical benefit of retifanlimab and pemigatinib in patients with advanced DDLPS

  evaluate clinical benefit of retifanlimab and pemigatinib in patients with advanced DDLPS

  2024-2028

Secondary Outcomes (4)

• To further evaluate clinical efficacy of retifanlimab and pemigatinib in DDLPS

  2024-2028

• To evaluate the safety and tolerability of pemigatinib and retifanlimab

  2024-2028

• To evaluate impact of treatment and disease status on quality of life

  2024-2028

• To evaluate the relationship between baseline and on-treatment biomarkers and clinical activity

  2024-2028

Study Arms (1)

Pemigatinib + Retifanlimab

EXPERIMENTAL

Patients will be treated with pemigatinib monotherapy for an induction phase of 6 weeks. This period is a safety measure to assess and manage adverse events of pemigatinib before start of combination treatment. Pemigatinib will be given daily as a 3-weekly cycle (2 weeks on followed by one week off) for 2 cycles. After 6 weeks, patients will receive combination treatment with retifanlimab (Q3W) and pemigatinib also as a 3-weekly cycle (2 weeks on followed by one week off).

Drug: Pemigatinib; Drug: Retifanlimab

Interventions

Pemigatinib DRUG

selective fibroblast growth factor receptor (FGFR) inhibitor, oral tablet

Pemigatinib + Retifanlimab

Retifanlimab DRUG

PD-1 inhibitor, Intravenous infusion

Pemigatinib + Retifanlimab

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Patient has received anticancer therapy within 28 days of the first administration of study treatment, with the exception of localized radiotherapy given to a lesion not considered for RECIST measurements.
• Toxicity of prior therapy that has not recovered to ≤ Grade 1 with the exception of
• Alopecia
• Peripheral neuropathy
• Anemia not requiring transfusional support
• 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. 6. Patients with a prior or concurrent malignant disease whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical trial are not eligible. Exceptions include, but are not limited to, patients with a history of breast cancer, requiring continued hormonal treatment (e.g. anti-estrogen or an aromatase inhibitor), patients with a history of prostate cancer, requiring continued support with luteinizing hormone- releasing hormone (LHRH) agonists, with or without androgens, basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• \. 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.
• \. Receiving chronic systemic corticosteroids (\> 10 mg/day of prednisone or equivalent):
• Notes:
• Physiologic corticosteroid replacement therapy at doses \> 10 mg daily of prednisone or equivalent for adrenal or pituitary insufficiency and in the absence of active autoimmune disease is permitted.
• Participants with a condition that requires intermittent use bronchodilators, inhaled steroids, or local steroid injections may be admitted (eg, asthma or chronic obstructive pulmonary disease exacerbation).
• Participants using topical, ocular, intra-articular, or intranasal steroids (with minimal systemic absorption) may be admitted.

Sponsors & Collaborators

• Lund University Hospital: lead

Study Sites (4)

Oslo University Hospital HF

Oslo, Norway

RECRUITING

Sahlgrenska University Hospital

Gothenburg, Sweden

RECRUITING

Skåne University Hospital

Lund, Sweden

RECRUITING

Karolinska Universitetssjukhuset

Stockholm, Sweden

RECRUITING

MeSH Terms

Conditions

Liposarcoma

Interventions

pemigatinib

Condition Hierarchy (Ancestors)

Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Central Study Contacts

Helena Nyström, MD

CONTACT

+46 46 17 75 20; helena.nystrom@skane.se

Liliya Shcherbina, PhD

CONTACT

liliya.shcherbina@skane.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2024
• First Posted: April 29, 2024
• Study Start: June 20, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: August 28, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1); SE (3)