Diwakar Davar, MBBS, MSc

I am currently an Associate Professor of Medicine, Clinical Director, Melanoma and Skin Cancer Program, and the Vice-Chief of Academic Affairs in the Division of Hematology-Oncology and Department of Medicine at University of Pittsburgh. My initial work established the role of high-dose IL-2, and immunomodulatory pegylated IFN (peg-IFN) in advanced metastatic melanoma.

Stemming from observational studies linking differences in the taxonomic composition of the gut microbiome to differential ICI outcomes in cancer patients, we developed the concept of "gut microbial communities (microbiotypes)" and their variable association with clinical outcomes to anti-PD-1, and how their non-uniform geographic distribution contributed to observed discrepancies between previously published cohorts (McCulloch and Davar, Nature Medicine 2023). Based on data implicating intestinal dysbiosis in mediating PD-1 non-response in melanoma, we studied responder-derived fecal microbiota transplant (FMT) in PD-1 refractory melanoma and demonstrated that microbiome modulation reversed resistance to immunotherapy (Davar, Science 2022). These results have prompted follow up trials evaluating microbiome modulation in ICI-refractory melanoma and NSCLC, along with treatment-refractory immune-related adverse events.

Innate pattern recognition receptors such as Toll-like receptor 9 (TLR9) agonists induce inflammatory responses that promote the killing of infectious microorganisms and cancer cells while augmenting adaptive immune responses. Studying novel TLR9 agonists in preclinical models, we demonstrated synergy between TLR9 agonists and immune checkpoint blockade in depleting intrahepatic myeloid-derived suppressor cells in preclinical models of liver metastases (Ghosh, J Immunother Cancer 2024). In the context of an investigator-initiated neoadjuvant study of TLR9 agonist vidutolimod with anti-PD-1 in high-risk resectable melanoma, we reported high pathologic response rates, and identified repolarized myeloid cells within the tumor, peripheral proteomic pharmacodynamic signature and distinct gut microbiota as biomarkers (Davar, Cancer Cell 2024).

Tim-3 is an immune checkpoint. TIM-3 expression on CD8+ T cells is associated with T cell dysfunction, and is also expressed on DCs, where it regulates NLRP3 inflammasome activation. Cobolimab (TSR-042) is a phosphotidylserine (PS) specific anti-TIM-3. In the phase I/II AMBER study, Cobolimab was studied at a variety of doses, with some activity in treatment-refractory melanoma and NSCLC, but more prominent activity in PD-1 naïve melanoma (Davar and Eroglu, Clin Cancer Res 2025 and Davar, Clin Cancer Res 2025).

I have contributed to the development of novel agents including PD-L1-dependent CD28 co-stimulator and dual PD-1/CTLA-4 inhibitor ALPN-202 (Davar, J Immunother Cancer 2024; Cavalcante, J Immunother Cancer 2024), MEDI5395 (Davar, J Immunother Cancer 2024) among others. My research interests lie in translational cancer immunotherapy and designing novel clinical trials to address important scientific questions. My goal is to have a career as a physician-scientist with a clinical practice focusing on melanoma and a translational career centered on designing early-phase clinical trials based on an improved understanding of tumor immunobiology and host-tumor-microenvironment interactions. In summary, I have a demonstrated record of accomplished and productive research projects in an area of high relevance for a population with a highly lethal disease.