Abstract CT205: Safety and preliminary activity of naptumomab estafenatox (NAP) and durvalumab in patients with advanced or metastatic solid tumors: interim results from a phase 1b trial

Background: NAP is a chimeric protein composed of a superantigen (SAg) and a Fab targeting the common tumor antigen 5T4. Its therapeutic effect is associated with activation, expansion and tumor infiltration of SAg-binding specific T cells. Durvalumab is a human monoclonal antibody that blocks programmed death ligand 1 (PD-L1).Initial data are reported from the dose escalation and MTD expansion parts of a phase 1b trial (NCT03983954), evaluating the safety and activity of NAP in combination with durvalumab in patients (pts) with advanced or metastatic solid tumors. Methods: The primary objective was evaluating safety, tolerability, MTD/RP2D of NAP in combination with durvalumab. Secondary objectives included efficacy and duration of response based on RECIST/iRECIST. Serum biomarkers were collected. Dose-escalation was used to determine the MTD/RP2D. The MTD was the highest dose at which less than one-third of evaluable patients experienced a dose-limiting toxicity. Patients were treated with NAP at 2, 5, 10, 15 and 20 mcg/kg and durvalumab at a flat dose (1120 mg) in 21 days cycles using 3+3 design. Obinutuzumab pretreatment was employed to inhibit the formation of anti-drug antibodies (ADAs) to NAP. Additional patients were enrolled at MTD; RP2D was determined based on the MTD, pharmacokinetics and biomarkers. Results: 59 pts were enrolled, median age was 62 yrs (34-88), 56% female, ECOG 0 in 47% and 1 in 53%. 69% had pancreatic, ovarian or TN breast cancers. Pts received a median of 3 prior lines (0-6) and 7 pts (12%) received prior CPIs. AEs reported in 57 pts (97%) and included grade 1-2 infusion related reactions (IRRs) in 85%. 95% of IRRs occurred in cycles 1-2 and were rapidly reversible. Grade 3 IRRs occurred in 10%. Transient grade 1-2 elevations in liver enzymes occurred in 25% of pts. Treatment was discontinued due to toxicities in 4 pts (7%), at doses above RP2D. 23 patients were treated at the RP2D (10mcg/kg). IRRs were reported in 21 pts (91%), grade 3 IRRs occurred in 4 pts, all limited to cycle 1. No pts discontinued treatment due to toxicities at the RP2D. 2 patients had CR (cervical who progressed on prior CPI and pancreatic cancer, 5 m and 35+ m respectively), 2 pts had PR (HCC who progressed on prior CPI and peritoneal mesothelioma, 24+ m and 13 m). Four pts (7%) had SD, with a median duration of 15 months (5-24+). Conclusions: NAP RP2D was reached at 10 mcg/kg. Antitumor activity with significant response duration was observed. Based o