Trial Title:
A Phase 2, Open Label Study of PEmigatinib and REtifanlimab in Advanced Dedifferentiated LIposarcoma (PERELI)
NCT ID:
NCT06389799
Condition:
Dedifferentiated Liposarcoma
Conditions: Official terms:
Liposarcoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pemigatinib
Description:
selective fibroblast growth factor receptor (FGFR) inhibitor, oral tablet
Arm group label:
Pemigatinib + Retifanlimab
Intervention type:
Drug
Intervention name:
Retifanlimab
Description:
PD-1 inhibitor, Intravenous infusion
Arm group label:
Pemigatinib + Retifanlimab
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
Participants will be eligible for the study if all of the following criteria are met:
1. Be 18 years of age or above, on day of signing informed consent.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Have a performance status of 0-2 on the ECOG Performance Scale.
9. 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)
10. 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.
11. 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.
12. 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.
Exclusion Criteria:
1. 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.
2. Toxicity of prior therapy that has not recovered to ≤ Grade 1 with the exception of
1. Alopecia
2. Peripheral neuropathy
3. Anemia not requiring transfusional support
4. Other toxicities may be considered acceptable (not an exclusion criteria) upon
discussion with the Sponsor.
3. 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.
4. Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
5. 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.
7. 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.
8. 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.
9. Receiving chronic systemic corticosteroids (> 10 mg/day of prednisone or
equivalent):
Notes:
1. 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.
2. 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).
3. Participants using topical, ocular, intra-articular, or intranasal steroids (with
minimal systemic absorption) may be admitted.
4. Brief course of corticosteroids for prophylaxis (eg, contrast dye allergy) or study
treatment-related standard premedication is permitted.
10. Has a history of organ transplant, including allogeneic stem cell
transplantation.
11. Has an active infection requiring systemic antibiotics or antifungal or
antiviral treatment within 7 days before first dose of study treatment.
12. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the
best interest of the subject to participate, in the opinion of the treating
Investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
14. 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 180 days after the last dose of trial treatment.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
16. Has received prior therapy with a selective FGFR inhibitor. 17. Has a known
history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV
RNA [qualitative] is detected).
19. Has received a live vaccine within 30 days of planned start of study therapy.
a. Note: COVID-19 vaccines are allowed. Seasonal influenza vaccines for injection are
generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines
(e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
20. 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 vessel due to
injury, disease, or aging in the absence of systemic mineral imbalance).
21. 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.
22. Has current evidence of clinically significant corneal (including, but not limited
to, bullous/band keratopathy, corneal abrasion, inflammation/ulceration,
keratoconjunctivitis) or retinal disorder (including, but not limited to,
macular/retinal degeneration, diabetic retinopathy, retinal detachment) as confirmed
by ophthalmologic examination 23. Has a history of hypovitaminosis D currently
requiring supraphysiologic doses (eg, 50,000 UI/weekly) to replenish the deficiency.
Vitamin D supplements are allowed.
Gender:
All
Minimum age:
18 Years
Maximum age:
100 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Oslo University Hospital HF
Address:
City:
Oslo
Country:
Norway
Status:
Not yet recruiting
Contact:
Last name:
Kjetil Boye, MD
Phone:
4722934000
Email:
kjetil.boye@rr-research.no
Facility:
Name:
Sahlgrenska University Hospital
Address:
City:
Göteborg
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Lina Hansson, MD
Phone:
46313427950
Email:
lina.hansson@vgregion.se
Facility:
Name:
Skåne University Hospital
Address:
City:
Lund
Country:
Sweden
Status:
Recruiting
Contact:
Last name:
Helena Nyström, MD
Contact backup:
Phone:
+4646177520
Email:
helena.nystrom@skane.se
Start date:
June 20, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
Lund University Hospital
Agency class:
Other
Source:
Lund University Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06389799
