Ratner, Lee
Mayo Clinic
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Citations 2
Defactinib, Pembrolizumab, and Gemcitabine in Patients with Advanced Treatment Refractory Pancreatic Cancer: A Phase I Dose Escalation and Expansion Study
Wang‐Gillam, Andrea , McWilliams, Robert R. , Suresh, Rama , Lockhart, A. Craig , Brown, Amberly , Breden, Marcus , Belle, Jad I. , Herndon, John M. , Bogner, Savannah J. , Tan, Benjamin , Boice, Nicholas , Acharya, Abhi , Abdiannia, Mina , Yoon, Harry H. , Zhu, Mojun , Aranha, Olivia , Herzog, Brett H. , Lim, Kian-Huat , McWilliams, Robert R , Suresh, Rama , Lockhart, Albert C , Brown, Amberly , Breden, Marcus , Belle, Jad I , Herndon, John , Bogner, Savannah J , Pedersen, Katrina , Tan, Benjamin , Boice, Nicholas , Acharya, Abhi , Abdiannia, Mina , Gao, Feng , Yoon, Harry H , Zhu, Mojun , Trikalinos, Nikolaos A , Ratner, Lee , Aranha, Olivia , Hawkins, William G , Herzog, Brett H , DeNardo, David G , Wang-Gillam, Andrea , Pedersen, Katrina S. , Gao, Feng , Trikalinos, Nikolaos A. , Ratner, Lee
Clinical Cancer Research | October 13, 2022 | Volume: 28 | Issue: 24 | Pages: 5254-5262
Abstract Purpose: Targeting focal adhesion kinase (FAK) renders checkpoint immunotherapy effective in pancreatic ductal adenocarcinoma (PDAC) mouse model. Defactinib is a highly potent oral FAK inhibitor that has a tolerable safety profile. Patients and Methods: We conducted a multicenter, open-label, phase I study with dose escalation and expansion phases. In dose escalation, patients with refractory solid tumors were treated at five escalating dose levels of defactinib and gemcitabine to identify a recommended phase II dose (RP2D). In expansion phase, patients with metastatic PDAC who progressed on frontline treatment (refractory cohort) or had stable disease (SD) after at least 4 months of standard gemcitabine/nab-paclitaxel (maintenance cohort) were treated at RP2D. Pre- and posttreatment tumor biopsies were performed to evaluate tumor immunity. Results: The triple drug combination was well-tolerated, with no dose-limiting toxicities. Among 20 treated patients with refractory PDAC, the disease control rate (DCR) was 80%, with one partial response (PR) and 15 SDs, and the median progression-free survival (PFS) and overall survival (OS) were 3.6 and 7.8 months, respectively. Among 10 evaluable patients in the maintenance cohort, DCR was 70% with one PR and six SDs. Three patients with SD came off study due to treatment- or disease-related complications. The median PFS and OS on study treatment were 5.0 and 8.3 months, respectively. Conclusions: The combination of defactinib, pembrolizumab, and gemcitabine was well-tolerated and safe, had promising preliminary efficacy, and showed biomarker activity in infiltrative T lymphocytes. Efficacy of this strategy may require incorporation of more potent chemotherapy in future studies.
AIDS-Related Kaposi Sarcoma, Version 2.2019
Suneja, Gita , Ambinder, Richard F. , Ard, Kevin L. , Baiocchi, Robert A. , Cohen, Adam K. , Crysler, Oxana , Gupta, Neel K. , Gustafson, Chelsea, Hall, Andre, Johung, Kimberly L. , LaCasce, Ann S. , Lin, Chi , Menon, Manoj , Morgan, David , Nathwani, Nitya , Ratner, Lee , Rizza, Stacey A. , Sanchez, Julian , Taylor, Jeff , Tomlinson, Benjamin , Wang, Chia-Ching J., Dwyer, Mary A., CGC, Freedman-Cass, Deborah A., Rizza, Stacey , Ratner, Lee , Reid, Erin G , Barta, Stefan K , Carchman, Evie H. , Klopp, Ann H. , Mehta, Amitkumar , Noy, Ariela , Rudek, Michelle A. , Yendamuri, Sai S , CGC, Freedman-Cass, Deborah A., Ambinder, Richard F
Journal of the National Comprehensive Cancer Network | February 20, 2019 | Volume: 17 | Issue: 2 | Pages: 171-189
As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin’s lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.