PankoMab-GEX (PMG) is a glyco-engineered humanized monoclonal antibody recognizing the carbohydrate-induced tumor-associated epitope mucin 1 (TA-MUC1). A phase I study showed safety and tolerability of PMG in patients with TA-MUC1 positive advanced solid malignancies. The aim of the present phase 2 study is to evaluate the efficacy and safety of maintenance therapy with PMG compared to placebo in patients with recurrent ovarian, fallopian tube or primary serous peritoneal cancer.
In this placebo-controlled phase 2 study PMG was given as switch maintenance therapy, after response or absence of tumor progression following chemotherapy (CT) in tumors that are TA-MUC1 positive on archival tissue. Stratification criteria are ‘resistance’ (progression-free survival (PFS) 0 - < 6 months) vs. ‘partial sensitivity‘(PFS 6-12 months) to the most recent platinum-based CT; number of prior CT lines (2 vs. 3-5); response or stable disease after last CT. Patients were randomized 2:1 to receive intravenous PMG (500mg and 1 week later a dose of 1700mg) or placebo (Pl) repeated every 3 weeks until tumor progression or toxicity. Primary endpoint is PFS by immune related response criteria (irRC) based on modified RECIST 1.1. Secondary endpoints include PFS and PFS at 6 months by RECIST, safety, overall response rate, CA125 progression; overall survival; QoL; pharmacokinetics.
From 2014 to 2016, 216 pts were randomized to PMG (n = 151) or placebo (Pl) (n = 65) (see demographics in table 1). No difference was observed for the primary endpoint of PFS by irRC (median 15.3 and 15.0 weeks for PMG and Pl respectively) [HR: 0.958 (95% CI: 0.690-1.331) p = 0.7988]. No advantage for PMG over Pl was observed for all other secondary efficacy endpoints and subgroup analysis by stratification factors. PMG was well tolerated, with grade 1-2 infusion related reactions being the most common AE.Table:
LBA41 Patient Demographics
|0||81 (54.4%)||30 (46.9%)||111 (52.1%)|
|1||68 (45.6%)||34 (53.1%)||102 (47.9%)|
|IIIC||55 (36.9%)||25 (39.1%)||80 (37.6%)|
|IV||51 (34.2%)||22 (34.4%)||73 (34.3%)|
|Response to previous treatment|
|CR/PR||87 (58.4%)||33 (51.6%)||120 (56.3%)|
|SD/NOT assessable||62 (41.6%)||31 (48.4%)||93 (43.7%)|
|Number of previous treatment|
|2||50 (33.6%)||24 (37.5%)||74 (34.7%)|
|≥3||99 (66.4%)||40 (62.5%)||139 (65.3%)|
|Duration of previous treatment|
|≤6 months||67 (45.0%)||27 (42.2%)||94 (44.1%)|
|>6 ≤12 months||82 (55.0%)||37 (57.8%)||119 (55.9%)|
This study shows that PMG switch maintenance does not improve outcome in ovarian cancer TA-MUC1 positive patients.
Clinical trial identification
Legal entity responsible for the study
U. De Giorgi: Speaker honorarium or travel support from Astellas, Janssen-Cilag and Sanofi-Aventis. N. Colombo: Attended advisory board meetings for Astra Zeneca, Roche, Pharmamar, Tesaro, Clovis, Pfizer, Advaxis. All other authors have declared no conflicts of interest.