Abstract 1027TiP
Background
The carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) has a number of important roles in the cancer phenotype, including angiogenesis, mediation of neutrophil extracellular trap activity, regulation of NK and CD8+ T-cells, the immune exclusion phenotype of therapy resistance, as well as regulation of TIM3. CM24 is an IgG4 which has been found to block CEACAM1 interactions and has been evaluated in an initial phase I trial (Shapira, R. et al., ASCO 2020) as a single agent at 7 dose levels ranging between 0.01mg/kg and 10mg/kg. No dose limiting toxicities were observed in this study and PK analysis suggested that CM24 doses higher than 10mg/kg should be administered q2w to obtain full receptor occupancy.
Trial design
The phase I/II (Clinical trial: NCT04731467) initiated in February 2021 and encompasses a dose escalation of CM24 from 10 to 20mg/kg administered q2w with nivolumab 480mg q4w for the treatment of refractory cancer patients, with the primary objective to evaluate safety, tolerability, PK and determine the recommended phase II dose (RP2D). During the dose escalation phase, patients are enrolled in dose cohorts in a conventional 3+3 design. This part will be followed by 2 expansion cohorts: the first includes patients with NSCLC refractory to first-line immunotherapy, receiving CM24 RP2D q2w in combination with nivolumab; the second includes patients with metastatic pancreatic adenocarcinoma whose disease progressed after first-line treatment, receiving CM24 RP2D q2w in combination with nab-paclitaxel and nivolumab. The primary objective of the expansion parts is ORR. CEACAM1 measurements in serum, biopsy specimens and TILs as well as tumor and TILs PDL1 levels will be evaluated as potential biomarkers. Blockade of CEACAM1 by CM24 in combination with nivolumab or nivolumab and nab-paclitaxel, may provide patients with refractory malignancies with an important treatment option. Preliminary safety and efficacy data from the study will be presented at the conference.
Clinical trial identification
NCT04731467.
Editorial acknowledgement
Legal entity responsible for the study
Purple Biotech Ltd. (FameWave Ltd.).
Funding
Purple Biotech Ltd. (FameWave Ltd.).
Disclosure
G. Markel: Financial Interests, Personal, Advisory Board, FameWave Ltd. is a fully owned subsidiary of Purple Biotech Ltd.: Purple Biotech. M. Schickler: Financial Interests, Personal, Full or part-time Employment, FameWave Ltd. is a fully owned subsidiary of Purple Biotech Ltd.: Purple Biotech Ltd. H. Reuveni: Financial Interests, Personal, Full or part-time Employment, FameWave Ltd. is a fully owned subsidiary of Purple Biotech Ltd.: Purple Biotech Ltd. L. Jin: Non-Financial Interests, Sponsor/Funding, BMS is a collaborator in the trial: Purple Biotech Ltd. B. Liang: Financial Interests, Personal, Full or part-time Employment, FameWave Ltd. is a fully owned subsidiary of Purple Biotech Ltd.: Purple Biotech Ltd. All other authors have declared no conflicts of interest.