Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

• Authors: Angus G Dalgleish, Justin Stebbing, Douglas Ja Adamson, Seema Safia Arif, Paolo Bidoli, David Chang, Sue Cheeseman, Robert Diaz-Beveridge, Carlos Fernandez-Martos, Rob Glynne-Jones, Cristina Granetto, Bartomeu Massuti, Karen McAdam, Raymond McDermott, Andrés J Muñoz Martín, Demetris Papamichael, Roberto Pazo-Cid, Jose M Vieitez, Alberto Zaniboni, Kevin J Carroll, Shama Wagle, Andrew Gaya, Satvinder S Mudan
• Journal: British journal of cancer (Br J Cancer) Vol. 115 Issue 7 Pg. 789-96 (09 27 2016) ISSN: 1532-1827 [Electronic] England
• PMID: 27599039 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Antimetabolites, Antineoplastic
• Biomarkers, Tumor
• Cancer Vaccines
• Deoxycytidine
• IMM-101
• Gemcitabine

Topics

• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic (administration & dosage, adverse effects, therapeutic use)
• Biomarkers, Tumor
• Cancer Vaccines (administration & dosage, adverse effects, therapeutic use)
• Carcinoma, Pancreatic Ductal (blood, drug therapy, secondary)
• Combined Modality Therapy
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Europe
• Female
• Humans
• Immunotherapy, Active
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Neoplasm Metastasis
• Pancreatic Neoplasms (blood, drug therapy, pathology)
• Treatment Outcome
• Gemcitabine