Retifanlimab (Anti-PD-1 Antibody) With Gemcitabine and Docetaxel in Patients With Advanced Soft Tissue Sarcoma

Eligibility Criteria

• * Diagnosis of metastatic or locally advanced and unresectable high-grade soft tissue sarcoma. Unresectable is defined as:
• 1. primary tumor cannot be safely removed surgically, or
• 2. primary tumor would benefit from systemic therapy prior to a surgical approach
• * Be willing and able to provide written informed consent
• * Must consent to mandatory tumor biopsy (if deemed safe and feasible) for research studies at screening, if archival tissue is not available, and at C1D15, C3D15.
• * Age ≥ 18 years
• * ECOG performance status ≤ 1
• * Presence of measurable disease per RECIST v1.1
• * Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment.
• * No prior systemic therapy (see exclusion criteria, below)
• * Negative serum pregnancy test in women of childbearing potential
• * Patients with chronic HBV (HBsAg-positive with undetectable or low HBV DNA and normal ALT, or HBsAg-negative with anti-HBc-positive serology) and HCV (completed curative antiviral treatment with HCV viral load below the limit of quantification) may be eligible
• * Patients with HBV should be treated with suppressive antiviral therapy prior to enrollment
• * Patients with HCV must have completed curative therapy and have negative HCV viral load
• * Adequate organ function, as defined in Table 2:
• * Received any systemic therapy in the advanced or metastatic setting
• * Adjuvant or neoadjuvant therapies received ≥ 1 year prior to enrollment are permitted
• * Unstable or deteriorating cardiovascular disease within the previous 6 months, including:
• * Unstable angina or myocardial infarction
• * CVA/stroke
• * New York Heart Association \[NYHA\] Class III or IV congestive heart failure
• * Uncontrolled clinically significant arrhythmias
• * Current use of immunosuppressive medication, EXCEPT for the following:
• * Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
• * Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent
• * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• * Evidence of clinically significant immunosuppression such as the following:
• * Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
• * Concurrent opportunistic infection
• * Receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 2 months prior to enrollment
• * History or evidence of symptomatic autoimmune disease in past 2 years prior to enrollment.
• * Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease
• * Uncontrolled HIV infection, as defined by one or more of the following:
• * Patients with CD4+ T-cell (CD4+) counts \< 350 cells/uL
• * Patients with a history of an opportunistic infection secondary to AIDS
• * Patients on anti-microbials with drug-drug interactions with the study drugs on this protocol, who cannot be switched to alternative anti-microbials
• * Patients on antiretroviral therapy \< 4 weeks
• * Patients with HIV viral load \> 400 copies/mL
• * Active Hepatitis B or Hepatitis C
• * Patients who have received a live vaccine within 30 days of the start date of the planned study therapy (with the exception of COVID-19 vaccines)
• * History of active TB (Bacillus Tuberculosis)
• * Radiation therapy within 2 weeks prior to study day 1
• * If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
• * Women who are pregnant or breast feeding
• * Patients expecting to conceive or father children within the projected duration of the trial, starting with the visit through 180 days after the last dose of study treatment(s)
• * Prior organ transplantation including allogenic stem-cell transplantation
• * Active infection requiring systemic therapy
• * Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3)
• * Patients with prior history of interstitial lung disease and clinically significant pulmonary compromise, including those who have a requirement for supplemental oxygen use to maintain adequate oxygenation