Nadunolimab (CAN04), a first-in-class monoclonal antibody against IL1RAP, in combination with chemotherapy in subjects with pancreatic cancer (PDAC) and non-small cell lung cancer (NSCLC)

Abstract

Background Interleukin-1 Receptor Accessory Protein (IL1RAP) is expressed on cancer and stromal cells in many tumors. IL-1 pathway is upregulated in response to cytotoxics as a survival signal. CAN04 targets IL1RAP, blocking IL-1α and β signaling and triggering antibody-dependent cellular cytotoxicity. CAN04 has been assessed as monotherapy without reaching maximum tolerated dose (Awada el al. ASCO 2019). We report the results of CAN04 in combination with gemcitabine/nab-paclitaxel (PDAC) and gemcitabine/cisplatin (NSCLC). Methods Primary objective was to determine safety of CAN04 in combination with standard of care chemotherapy. Efficacy by iRECIST is a secondary endpoint. Initial CAN04 dose was 5 mg/kg weekly. Priming dose of 0.5 mg/kg was given on Day -7 to reduce the risk of infusion related reaction (IRR). Results 58 pts were available for safety analysis: 36 with PDAC (enrollment completed) and 22 with NSCLC (enrollment ongoing). Median age 58 years (39-87), 45% female, 60% ECOG 0, 87% stage IV. PDAC patients were all first line; 9 (41%) of NSCLC patients had received previous pembrolizumab monotherapy. G1/2 IRRs were observed in 40% (G3 3%); 61% occurred at the priming dose. Most frequent (>10%) G3/4 adverse events (AE): neutropenia 64%, thrombocytopenia 24%, infection 24%, febrile neutropenia 19%, and anemia 17%. In 33 PDAC evaluable patients, Objective response rate (ORR) is 27%, clinical benefit rate 57.6%. Median duration of response (DoR) 6.5 mo (range 1.9 to 13.8). 5 pts with initial PD at first evaluation showed benefit beyond progression per iRECIST with concomitant CA19-9 reduction. iPFS per iRECIST is 7.8 mo [95% CI: 5.2-10.2] with 50% of events. Median OS is 12.6 mo [95% CI not estimable] and 1-year survival 55%. 15 NSCLC pts are so far included in the efficacy analysis. ORR is 60% (1 CR, 6 confirmed PR, 2 unconfirmed PR ongoing), median DoR is 6.2 mo (3.4 to 18.7). Median PFS is 8.2 mo [...].