Interim results of the randomized phase 2 cohort of study FW-2020-01 assessing the efficacy, safety and pharmacodynamics of CM24 in combination with nivolumab and chemotherapy in advanced/metastatic pancreatic cancer.
Authors: Macarulla Teresa , Cecchini Michael , Garcia-Carbonero Rocio , Golan Talia , Perets Ruth , Borazanci Erkut Hasan , Pedregal Manuel , Ponz-Sarvise Mariano , Al Hallak Mohammed Najeeb , Pant Shubham , Boni Valentina , Saavedra Omar , de Miguel Maria J. , Leal Alexis Diane , Muñoz Martín Andrés J. , Sauri Tamara , Schickler Michael 
Published: June 2024

LBA4143 Background: The novel monoclonal antibody CM24 blocks the activity of Carcinoembryonic Antigen Cell Adhesion Molecule 1 (CEACAM1), known to have key roles in cancer progression, immune evasion, and metastasis. We present the interim efficacy and safety data from the global multi-center, open label, randomized Phase 2 study (NCT 04731467) in patients (pts) with advanced/metastatic pancreatic ductal adenocarcinoma (PDAC) who progressed after 1st line therapy, treated with CM24, nivolumab (nivo) and chemotherapy vs. chemotherapy (CH). Methods: Patients with advanced/metastatic PDAC progressing after 1 prior line of systemic therapy including fluoropyrimidine/irinotecan or gemcitabine/nab-paclitaxel, having ≥1 measurable lesion, ≥18-year-old, ECOG ≤1 and adequate organ function were randomized 1:1 based on the class of prior CH received. Randomization was either to the experimental groups (EX) receiving CM24 (20mg/kg, q2wk), nivo (240mg/kg, q2wk) with one of the following CH regimens, liposomal irinotecan, 5 fluorouracil and leucovorin (Nal-IRI; q2wk) or gemcitabine/nab-paclitaxel (gem/nab; q1wk x3) or the control groups (C) with one of the CH regimens alone. This is a Bayesian design with an overall planned sample size of 60 pts with Overall Survival (OS) as the primary endpoint. Secondary endpoints include progression free survival (PFS), objective response rate (ORR) and disease control rate (DCR). An interim estimate of PFS HR, ORR and DCR based on data cut-off date of 21 Feb 2024 is reported. The analysis compares the EX vs. the respective C arm using log-rank test stratified by CH regimen. Results: A total of 63 PDAC pts were evenly randomized across the study arms. At data cut-off date, a total of 18 pts, 9 per treatment regimen remain on treatment. The median follow-up time for the Nal-IRI regimen is 6.3 months (95% CI: 5.5-8.4) and 5.2 months (95% CI: 4.0-6.7) for the gem/nab regimen. Median PFS ORR and DCR for the Nal-IRI EX arm were 3.8m (1.9-5.1; HR 0.70; p=0.213), 18.8% and 62.6%, and for the Nal-IRI C arm 1.9m (1.8-5.6), 6.3% and 40%, respectively (Table). Data for the gem/nab regimen and OS data for both regimens are not mature. Overall Grade ≥3 AE rate was 50% in the Nal-IRI EX arm and 13% in the C arm. The most common treatment-emergent grade ≥3 AEs EX vs. C were diarrhea (18.8% vs 6.7%), fatigue (18.8% vs 6.7%) and anemia (6.3% vs 0%). Conclusions: The interim analysis suggests that the combination of CM24/nivo/Nal-IRI/5FU/LV has a manageable safety profile with a longer PFS supported by higher ORR and DCR. OS Data continues to mature and will be reported once available. Clinical trial information: NCT04731467 . [Table: see text]