Phase I/II Study of PDS01ADC Monotherapy and in Combination With M7824 in Advanced Kaposi Sarcoma
Background: Kaposi sarcoma (KS) tumors grow on the skin, lymph nodes, lungs, bone, and gastrointestinal tract. KS often affects people with immune deficiencies, such as among people living with HIV or those with prior history of transplant. Researchers want to see if 2 non-chemotherapy drugs can help people with KS. NHS-IL12 triggers the immune system to fight tumors. M7824 blocks the pathways that cancer cells use to stop the immune system from fighting tumors.
Objective: To learn if giving NHS-IL12 alone or with M7824 could help the immune system fight KS tumors.
Eligibility: People 18 and older with KS that has been treated with chemotherapy or immunotherapy
Design: Participants will be screened with some or all of the following: medical history physical exam chest X-ray computed tomography scan blood and urine tests electrocardiogram and echocardiogram skin KS lesion biopsy lung exam gastrointestinal exam All participants will get NHS-IL12 every 4 weeks for up to 96 weeks (or 24cycles). It is injected under the skin. Some participants will also get M7824 every 2 weeks for up to 96 weeks (or 24cycles). It is given through a plastic tube that is put in an arm vein. Participants will complete questionnaires about how KS affects their quality of life. Their KS lesions will be measured and photographed. They will repeat some of the screening tests. They will give saliva samples or additional tissue samples. They will have a lung function test. Their ability to perform their normal activities will be assessed. The treatment duration is up to 96 weeks (or 24cycles) with an option to take NHS-IL12 and/or M7824 until the KS tumors are not responding, or you develop unacceptable side effects. Participants will have follow-up visits 7 and 30 days after treatment ends, then every 3 to 6 months for the next 18 months, then once a year for 3 years.
• Individuals with biopsy proven (confirmed in the Laboratory of Pathology, CCR) Kaposi sarcoma (KS)
• KS requiring systemic therapy, with or without history of prior KS therapy:
‣ T1 KS or T0 KS sufficiently widespread that systemic therapy is advisable, or KS affecting quality-of-life due to local symptoms or psychological distress
∙ OR,
• KS with an inadequate response to liposomal doxorubicin, paclitaxel, other systemic chemotherapy (either progressive disease or stable disease after 3 or more cycles) or immunotherapy (progressive disease)
‣ A wash-out period off treatment of 2 weeks from last chemotherapy and 4 weeks from last immunotherapy, other systemic treatment with a biologic agent, or monoclonal antibody therapy will be required in individuals with prior KS therapy.
⁃ Resolution of toxicity from prior therapy to \<= Grade 1.
⁃ At least five measurable cutaneous KS lesions with no previous local radiation, surgical or intralesional cytotoxic therapy that would prevent response assessment for that lesion.
⁃ Measurable disease by the criteria proposed by the AIDS Clinical Trials Group (ACTG) Oncology Committee for KS
⁃ HIV positive or negative.
⁃ ART for HIV+ individuals for 8 or more weeks prior to entry with an HIV viral load of \<400 copies/ml at screening and CD4+ T cell count of \>= 50 cells/microliter as this may be expected if individuals have received several courses of chemotherapy.
⁃ Age \>=18 years.
⁃ ECOG performance status \<=2 (Karnofsky \>=60%).
⁃ Adequate organ and marrow function as defined below:
• Absolute neutrophil count \>=1,000/mcL
• Platelets \>=100,000/mcL
• Total bilirubin within normal institutional limits; OR \<3x institutional ULN for Gilbert s syndrome or HIV protease inhibitors; OR \<5x ULN and direct bilirubin \< 0.7mg/dL for individuals on atazanavir-containing HIV regimen
• AST(SGOT)/ALT(SGPT) \<=1.5 X institutional upper limit of normal
• Hemoglobin \>= 9g/dL
• Creatinine within normal institutional limits OR creatinine clearance \>30 mL/min/1.73m\^2 as estimated by either Cockroft-Gault of 24- hour urine collection if creatinine levels above institutional normal
‣ Normal international normalized ratio (INR), PT\<=1.5 x ULN and activated partial thromboplastin time (aPTT) \<= 1.5 x ULN
⁃ The effects of PDS01ADC and M7824 on the developing human fetus are unknown. For this reason, individuals of child-bearing potential (IOCBP) and individuals able to father a child must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during treatment and for at least 4 months after the last dose of treatment and agree to inform the treating physician immediately if they become pregnant. Also, there is unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with M7824 and/or PDS01ADC, therefore IOCBP must agree to discontinue nursing if treated with these agents.
⁃ Ability of individual to understand and the willingness to sign a written informed consent document.