5537 Background: Ovarian cancer (OC) is a high medical need disease. Most patients (pts) relapse following initial therapy with limited therapeutic options. IMAB027 is the first-in-class monoclonal antibody (mAB) directed against claudin 6 (CLDN6), a cancer cell specific, embryonic tight junction protein and cancer stem cell marker. CLDN6 is expressed in > 55% of OCs and frequently in other cancer types. In preclinical models, IMAB027 executes potent anti-tumor activity via AB-dependent cellular cytotoxicity and complement-dependent cytotoxicity without mediating off-target toxicity. Methods: This first-in-human, open-label, dose escalation Phase I/II trial assesses the safety/tolerability (NCI-CTCAEv4.0), pharmacokinetics (PK) and clinical efficacy (RECIST 1.1) of IMAB027 in pts with advanced, recurrent CLDN6+ OC. Here we report preliminary data on 12 pts enrolled in the Phase I part of the study as of August 15, 2014. Pts received 100, 300, 600, or 1000 mg/m2 IMAB027 (n = 3/group) q3w IV until disease progression. Results: Pts had a median age of 64 (54–75) years, platinum-resistant disease and had received a median of 4 (3–9) lines of previous chemotherapies. All administered doses were safe and well tolerated, no DLT was observed and the MTD was not reached. 108 AEs have been recorded, all but 5 (4 grade [gr] 3, 1 gr 4) were gr 1–2 (82 and 21 AEs, respectively). 29 AEs were considered IMAB027 related (22 gr 1, 6 gr 2, 1 gr 3 as deemed by investigator). Five AEs (all in 1 pt) were classified as SAEs incl. one gr 2 hypersensitivity (study drug-related SUSAR). IMAB27-related SAEs were manageable and fully resolved. IMAB027 PK was well described with a 2-compartment model (mean AUC: 20,770–86,160 µg/mL×h; mean Cmax: 151–611 µg/mL for 300–1000 mg/m2). First signs of IMAB027 clinical activity were observed. Conclusions: This is the first clinical study to show effects of a therapy targeting CLDN6. Based on these preliminary Phase I data, IMAB027 may present a safe and well tolerated treatment option for women with recurrent, advanced OC. This warrants further clinical evaluation of IMAB027 in this patient population with a high medical unmet need. Clinical trial information: NCT02054351.
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Şahin et al. (2015) studied this question.