Relacorilant (RELA) with nab-paclitaxel (NP): Safety and activity in patients with pancreatic ductal adenocarcinoma (PDAC) and ovarian cancer (OvCA).

person Pamela N. Munster University of California San Francisco, San Francisco, CA info_outline Pamela N. Munster, Jasgit C. Sachdev, Gini F. Fleming, Erkut Hasan Borazanci, Jennifer A. Grabowsky, Manish Sharma, Joseph Custodio, Andrew Greenstein, Lawrence Lu, Dat Nguyen, Stacie Peacock Shepherd

Authors person Pamela N. Munster University of California San Francisco, San Francisco, CA info_outline Pamela N. Munster, Jasgit C. Sachdev, Gini F. Fleming, Erkut Hasan Borazanci, Jennifer A. Grabowsky, Manish Sharma, Joseph Custodio, Andrew Greenstein, Lawrence Lu, Dat Nguyen, Stacie Peacock Shepherd Organizations University of California San Francisco, San Francisco, CA, HonorHealth Research Institute/TGen, Scottsdale, AZ, The University of Chicago Medicine, Chicago, IL, HonorHealth Research Institute, Scottsdale, AZ, UC San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, University of Chicago, Chicago, IL, Corcept Therapeutics, Menlo Park, CA Abstract Disclosures Research Funding Other Background: Glucocorticoid receptor (GR) pathway activation has been linked with chemotherapy resistance (CTR). RELA (formerly CORT125134, Corcept Therapeutics), a potent selective GR modulator, in combination with paclitaxel reduced CTR and enhanced activity against tumor growth in preclinical models of solid tumors. Methods: Patients (pts) with advanced solid tumors, ≤3 prior lines of cytotoxic therapy, ECOG status 0-1, and adequate marrow function received RELA (100, 150, or 200mg) + NP (60, 80, or 100mg/m 2 ). Once daily RELA was given either continuously (CON) or intermittently (INT) (day before, of, and after NP). NP was dosed weekly for 3 of 4 weeks (wks) of a 28-day cycle. Prior NP therapy was allowed. Results: 72 pts have been enrolled [mean age 60 (range 18-81), mean number of prior therapies 3, prior taxane (TXN) treatment 54/72 (75%)]. 61 pts received ≥1 dose of RELA. Grade ≥3 AE ≥10% for CON: neutropenia (6/43, 14%); INT: neutropenia (6/18, 33%), anemia (2/18, 11%), and mucosal inflammation (2/18, 11%). Prophylactic G-CSF became mandatory in later cohorts. Recommended Phase 2 Dose: RELA 100mg-CON/150mg-INT + NP 80mg/m 2 (exposures similar to NP 100mg/m 2 due to CYP3A4 inhibition by RELA). Disease control (DC) > 24 wks was noted in 5/27 (19%) PDAC pts: 3 PR, 2 SD (27-50 wks). 3 pts achieved benefit despite progression on prior TXN with time to progression (TTP) 1.9-3.6x longer than prior TXN. 4/13 (31%) OvCA pts had DC > 24 wks: 1 CR, 1 PR, 2 SD (33-54+ wks). 1 pt had TTP 4.4x longer than prior TXN. 3 additional PRs were observed: acinar pancreatic cancer, TTP 31 wks (4.4x prior TXN); vulvar SCC HPV+, TTP 55 wks (3.9x prior TXN); cholangiocarcinoma, DC 29+ wks. Expression of GR-regulated genes involved in inflammation, apoptosis, and CTR distinguished pts with DC from pts without DC, providing proof of mechanism. Conclusions: RELA+NP resulted in durable disease control in pts with metastatic PDAC, OvCA, and other solid tumors, including those that have progressed on prior TXN. TTP was often several-fold longer than previously achieved on TXN therapy. Toxicities are manageable with prophylaxis for neutropenia. Further evaluation in OvCA NCT03776812, PDAC, and others are planned. Clinical trial information: NCT02762981