Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer.
Immune Modulation and Gemcitabine Evaluation-1, a randomised, open-label, phase II, first-line, proof of concept study (NCT01303172), explored safety and tolerability of IMM-101 (heat-killed Mycobacterium obuense; NCTC 13365) with gemcitabine (GEM) in advanced pancreatic ductal adenocarcinoma.



Patients were randomised (2 : 1) to IMM-101 (10 mg ml(-l) intradermally)+GEM (1000 mg m(-2) intravenously; n=75), or GEM alone (n=35). Safety was assessed on frequency and incidence of adverse events (AEs). Overall survival (OS), progression-free survival (PFS) and overall response rate (ORR) were collected.



IMM-101 was well tolerated with a similar rate of AE and serious adverse event reporting in both groups after allowance for exposure. Median OS in the intent-to-treat population was 6.7 months for IMM-101+GEM v 5.6 months for GEM; while not significant, the hazard ratio (HR) numerically favoured IMM-101+GEM (HR, 0.68 (95% CI, 0.44-1.04, P=0.074). In a pre-defined metastatic subgroup (84%), OS was significantly improved from 4.4 to 7.0 months in favour of IMM-101+GEM (HR, 0.54, 95% CI 0.33-0.87, P=0.01).



IMM-101 with GEM was as safe and well tolerated as GEM alone, and there was a suggestion of a beneficial effect on survival in patients with metastatic disease. This warrants further evaluation in an adequately powered confirmatory study.
Cancer Vaccine Institute, St George's University of London, London, UK.
Angus G
AG
Dalgleish
Department of Oncology, Imperial College, Hammersmith Hospital, London, UK.
Justin
J
Stebbing
Department of Oncology, Ninewells Hospital, Dundee, UK.
Douglas Ja
DJ
Adamson
Velindre Cancer Centre, Cardiff, UK.
Seema Safia
SS
Arif
Department of Oncology, Azienda Ospedaliera San Gerardo, Monza, Italy.
Paolo
P
Bidoli
Department of General Surgery, Royal Blackburn Hospital, Blackburn, UK.
David
D
Chang
Department of Oncology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK.
Sue
S
Cheeseman
Médico Adjunto de Oncología Médica, Hospital La Fe de Valencia, Valencia, Spain.
Robert
R
Diaz-Beveridge
Instituto Valenciano de Oncologia, Valencia, Spain.
Carlos
C
Fernandez-Martos
Mount Vernon Cancer Centre, Northwood, UK.
Rob
R
Glynne-Jones
Medical Oncology, Azienda Ospedaliera Santa Croce e Carle, Cuneo, Italy.
Cristina
C
Granetto
Ensayos Clínicos Oncología, Hospital General Universitario de Alicante, Alicante, Spain.
Bartomeu
B
Massuti
Oncology Department, Peterborough and Stamford Hospitals NHS Trust, Peterborough, UK.
Karen
K
McAdam
Medical Oncology, St Vincent's University Hospital and The Adelaide and Meath Hospital, Dublin, Republic of Ireland.
Raymond
R
McDermott
Gastrointestinal Cancer Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Andrés J Muñoz
AJ
Martín
Department of Medical Oncology, Bank of Cyprus Oncology Centre, Nicosia, Cyprus.
Demetris
D
Papamichael
Servicio de Oncología Médica, Hospital Miguel Servet, Zaragoza, Spain.
Roberto
R
Pazo-Cid
Area and Neuroendocrine Tumors Gastrointestinal Medical Oncology, Hospital Central de Asturias, Asturias, Spain.
Jose M
JM
Vieitez
Oncology Department, Fondazione Poliambulanza, Brescia, Italy.
Alberto
A
Zaniboni
TranScrip Partners LLP, Reading, UK.
Kevin J
KJ
Carroll
TranScrip Partners LLP, Reading, UK.
Shama
S
Wagle
Clinical Oncology, Guy's & St Thomas' Hospitals NHS Trust, London, UK.
Andrew
A
Gaya
St George's University of London, Imperial College, London and The Royal Marsden Hospital, London, UK.
Satvinder S
SS
Mudan
D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000188:drug therapy* / Q000556:secondary; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D016233:Immunotherapy, Active; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D019496:Cancer Vaccines; D003841:Deoxycytidine; C574749:IMM-101; D000093542:Gemcitabine