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
Authors: Geva Ravit , Stemmer Salomon , Perets Ruth , Maurice-Dror Corinne , Ben-Ami Eitan , Raphael Ari , Kumar Sanjeev , Lorber Ilana , Kedem Tal Hetzroni , Fields Scott Z. , Rozencweig Marcel , Golan Talia 
Published: April 2023

Abstract
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 on the favorable safety profile and prolonged responses, including CRs, in patients where response from a single agent CPI may not be expected, further evaluation of this combination is warranted including patients who have received prior CPI therapy.
Citation Format: Ravit Geva, Salomon Stemmer, Ruth Perets, Corinne Maurice-Dror, Eitan Ben-Ami, Ari Raphael, Sanjeev Kumar, Ilana Lorber, Tal Hetzroni Kedem, Scott Z. Fields, Marcel Rozencweig, Talia Golan. 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 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT205.