Annals of Oncology 26 (Supplement 8): viii1–viii4, 2015 doi:10.1093/annonc/mdv513.3
poster discussion 3PD
PEGylated human IL-10 (AM0010) in advanced solid tumors
A. Naing1, J.R. Infante2, K. Papadopoulos3, K. Autio4, P. Ott5, D. Wong6, G. S. Falchook7, M.R. Patel8, S. Pant9, M. Oft10 1 Investigational Cancer Therapeutics, MD Anderson Cancer Center, Houston, TX, USA 2 Drug Development, Sarah Cannon Research Institute / Tennessee Oncology, PLLC, Nashville, TN, USA 3 Clinical trials, START Center for Cancer Care, San Antonio, TX, USA 4 Department of Medicine, Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA 5 Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, MA, USA 6 Medicine, Hematology & Oncology, University of California Los Angeles (UCLA), Los Angeles, CA, USA 7 Drug Development, Sarah Cannon Research Institute at HealthONE, Denver, CO, USA 8 Cattlemen Office, Florida Cancer Specialists, Tampa, FL, USA 9 Stephenson Cancer Center, Oklahoma University, Oklahoma City, OK, USA 10 Clinical Research, ARMO BioSciences, Redwood City, CA, USA
abstracts
Aim: PEGylated IL-10 induces tumor rejection in mice and establishes immunological memory. We conducted a Phase I study to establish the safety and anti-tumor-activity of AM0010.
Methods: One hundred and forty three patients with advanced tumors including melanoma, renal cell (RCC), colorectal (CRC), prostate, ovarian and pancreatic cancer (PDAC) were enrolled in escalation cohorts and expansion cohorts (1 to 40 µg/kg). AM0010 was self-administrated daily subcutaneously. PK, anti-drug antibodies and immune responses were monitored. Patients had a median of 3 prior regimens (0-11) for advanced or metastatic disease. Results: 20 µg/kg was established as therapeutically active and the recommended phase 2 dose (RP2D). The maximum tolerated dose was not reached. Treatment-related adverse events (TrAE) included injection site reaction, rash, fatigue, anorexia, fever, flu-like symptoms, nausea, thrombocytopenia and anemia. Most adverse events were low grade. G3 TrAE events included anemia, thrombocytopenia, nausea, increased lipase, dyslipidemia, and transaminitis. Only one patient discontinued treatment due to TrAEs. Prolonged immune related AEs were not observed. In monotherapy, partial responses (PR) were observed in patients with RCC, melanoma and lymphoma. Of 16 evaluable patients with RCC (at RP2D), 19% had a PR and 81% had disease control. Disease control rate with or without tumor reductions was observed in several other indications, including patients with pancreatic (50%), lung (33%), ovarian (75%) or colon cancer (27%). Prolonged disease stabilization was observed in several patients including a CRC patient (>17months) and a PDAC patient (>11months). At RP2D AM00010 induced a characteristic Th1-Th2 immune activation signature in the serum: IL-18, IFNg, IL-4, GM-CSF, IL-7 and FasL and a reduction of TGFβ. AM0010 treatment increased activated PD-1 positive CD8 T cells in circulation and in the tumor tissue. Conclusions: In monotherapy, AM0010 has a well-tolerated safety profile and produces durable tumor responses accompanied by systemic immune stimulation. The pharmacodynamics and clinical activity observed support the ongoing combination with checkpoint inhibitors and chemotherapies. Disclosure: M. Oft: Ownership: ARMO BioSciences. All other authors have declared no conflicts of interest.
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