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

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
• •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.
• •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.