LBA41 - A Double-blind, placebo-controlled, randomized, phase 2 study to evaluate the efficacy and safety of switch maintenance therapy with the anti-TA-MU...

Date 08 September 2017
Event ESMO 2017 Congress
Session Gynaecological cancers
Topics Ovarian Cancer
Immunotherapy
Gynaecological Malignancies
Therapy
Presenter Jonathan Ledermann
Citation Annals of Oncology (2017) 28 (suppl_5): v605-v649. 10.1093/annonc/mdx440
Authors J. Ledermann1, J. Sehouli2, B. Zurawski3, F. Raspagliesi4, U. De Giorgi5, S. Banerjee6, J. Arranz Arija7, M. Romeo Marin8, A. Lisyanskaya9, R.L. Póka10, S. Mihutiu11, J. Markowska12, C. Cebotaru13, A. Casado Herraez14, N. Colombo15, N. Kovalenko16, E. Kutarska17, M. Hall18, R. Belli19, A. Zurlo19
  • 1Gynaecological Oncology, UCL Cancer Institute, University College London, WC1E6BT - London/GB
  • 2Department Of Gynecology And Gynecologic Oncology, Charité Campus Virchow Klinikum, Berlin/DE
  • 3Oncology Department, Franciszek Lukaszczyk Oncology Center, Bydgoszcz/PL
  • 4Gynecologic Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan/IT
  • 5Department Of Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, 47014 - Meldola/IT
  • 6Gynaecology Unit, Royal Marsden Hospital NHS Foundation Trust, SW3 6JJ - London/GB
  • 7Medical Oncology, Hospital General Universitario Gregorio Marañon, 28007 - Madrid/ES
  • 8Medical Oncology, Catalan Institute of Oncology (ICO Badalona), Hospital Germans Trias i Pujol, 8916 - Badalona/ES
  • 9Department Of Oncogynecology, St.-Petersburg Oncological City Hospital, 198255 - St.-Petersburg/RU
  • 10Gynaecologic Oncology, Debrecen University Clinical Center, 4032 - Debrecen/HU
  • 11Oncology Department, SPITALUL CLINIC MUNICIPAL "DR GAVRIL CURTEANU", 410469 - Oradea/RO
  • 12Klinika Onkologii, ODDZIAL GINEKOLOGII ONKOLOGICZNEJ, 60-569 - Poznan/PL
  • 13Radioterapie, INSTITUTUL ONCOLOGIC "PROF DR IOAN CHIRICUTA", 400015 - Cluj-Napoca/RO
  • 14Department Of Medical Oncology, Hospital Clinico Universitario San Carlos, 28040 - Madrid/ES
  • 15Division Of Medical Gynecologic Oncology, European Institute of Oncology and University of Milano-Bicocca, Milan/IT
  • 16Oncology Department, Volgograd Regional Oncology Dispensaryc No. 3, 404130 - Volzhskiy/RU
  • 17Iii Oddzial Ginekologii Onkologicznej, CENTRUM ONKOLOGII ZIEMI LUBELSKIEJ, PL-20-090 - Lublin/PL
  • 18Mount Vernon Cancer Centre, East and North Hertfordshire NHS Trust, HA6 2RN - Middlesex/GB
  • 19Clinical Development, Glycotope GmbH, 13125 - Berlin/DE

Abstract

Background

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.

Methods

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.

Results

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

PankoMabPlaceboOverall
Age61.261.261.2
ECOG
081 (54.4%)30 (46.9%)111 (52.1%)
168 (45.6%)34 (53.1%)102 (47.9%)
Tumor Stage
IIIC55 (36.9%)25 (39.1%)80 (37.6%)
IV51 (34.2%)22 (34.4%)73 (34.3%)
Response to previous treatment
CR/PR87 (58.4%)33 (51.6%)120 (56.3%)
SD/NOT assessable62 (41.6%)31 (48.4%)93 (43.7%)
Number of previous treatment
250 (33.6%)24 (37.5%)74 (34.7%)
≥399 (66.4%)40 (62.5%)139 (65.3%)
Duration of previous treatment
≤6 months67 (45.0%)27 (42.2%)94 (44.1%)
>6 ≤12 months82 (55.0%)37 (57.8%)119 (55.9%)

Conclusions

This study shows that PMG switch maintenance does not improve outcome in ovarian cancer TA-MUC1 positive patients.

Clinical trial identification

: NCT01899599

Legal entity responsible for the study

Glycotope GmbH

Funding

Glycotope GmbH

Disclosure

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.