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

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(-1) 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.