Clinical and Immune Evaluation of Establishing T Cell Immunity In Immunologically Cold Tumors

To perform  investigator-initiated clinical trials testing novel approaches to establish T cell immunity against advanced cancer in refractory patients.

Goals:

• Establish clinical and immune impact of radiation therapy and checkpoint blockade in patients with advanced disease
• Establish clinical and immune impact of CD40 agonists in combination with chemotherapy and checkpoint blockade in patients with advanced disease
• In each trial, determine safety and tolerability, assess T cell response, perform tissue-driven assessment of changes in TME and patterns of resistance

Accomplishments:

• Clinical trial of hypofractionated radiation therapy with CTLA4 and PDL1 mAb has been initiated at Penn, with 18 patients treated to date.
• Phase Ib/II clinical trial of chemotherapy with CD40 agonist mAb +/- nivolumab is open as a PICI wide study. Dr Vonderheide is overall PI and R Mick is lead biostatistician. Dr. O’hara is Penn site PI. PICI is IND sponsor. First cohort has completed enrollment (View Trial)

Project Participants:  Robert Vonderheide, Mark O’Hara, Nune Markosyan, Roger Cohen, Rosie Mick, Amit Maity, Kate Nathanson, John Wherry, and Andy Minn