Medical Writer: Drs. Stijn van den Borne
09 September 2016

Pancreatic Cancer

Cancer Vaccine IMM-101 Plus Gemcitabine Shows Hopeful Results in Metastatic Pancreatic Cancer

A phase II proof-of-concept (POC) study investigating the safety and tolerability of immune modulator IMM-101 plus gemcitabine vs. single agent gemcitabine in advanced pancreatic ductal adenocarcinoma (PDAC) showed significant improved progression-free survival (PFS) and overall survival (OS) in metastatic patients receiving the combination treatment.

“Real-world studies report the overall median survival from [advanced PDAC] diagnosis to be 4.6 months; in patients with metastatic cancer the median survival ranges between 2.8 and 5.7 months.”

About IMM-101

IMM-101 contains heat‐inactivated Mycobacterium obuense. Pre-clinical and clinical studies suggest IMM-101 can invoke an immune-modulatory response resulting in the release of cancer antigens, increased immune reactivity, decreased immunosuppression, and activation of immune cells known to have an anti-cancer effect.

“Only 18% of patients with advanced PDAC remain alive at one year, and 4% at five years […] Real-world studies report the median overall survival from diagnosis to be 4.6 months; in patients with metastatic cancer, the median survival ranges between 2.8 and 5.7 months.” said the authors.

On the choice for gemcitabine monotherapy as comparator arm, the authors commented that “Gemcitabine was the standard of care for advanced PDAC and at that time [of study start] it was widely used as the comparator arm in clinical trials for this disease.”

Study Design

110 adult patients with confirmed inoperable PDAC and at least one measurable lesions at a previously not irradiated site who had a WHO performance status (PS) 0–2 were randomised 2:1 in this open-label, phase II trial at 20 institutions in 5 European countries.

The study knew two pre-defined subgroups, 1) patients with metastatic disease; and 2) patients with locally advanced disease. Results of the latter subgroup were affected by small sample size, as only 16% of patients had locally advanced disease.

PFS Results

PFS favoured the combination IMM-101 plus gemcitabine in both the ITT and metastatic subgroup populations. In the ITT group, PFS for IMM-101 plus gemcitabine was 4.1 months vs. 2.4 months in the gemcitabine monotherapy arm (HR 0.58; 95% CI, 0.37-0.91; P=0.016).

In the metastatic subgroup, PFS was 4.4 months vs. 2.3 months favouring the IMM-101 combination arm over the gemcitabine monotherapy arm (HR 0.46; 95% CI, 0.28-0.75; P=0.001).

OS Results

In the overall, intent-to-treat (ITT) population, median OS was not significant with 6.7 months vs. 6.6 months for IMM-101 plus gemcitabine vs. gemcitabine respectively. It must be noted the hazard ratio (HR) numerically favoured the IMM-101 combination arm (HR=0.68; 95% CI, 0.44–1.04; P=0.074).

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However, in the pre-defined metastatic subgroup which consisted of 84% of ITT patients, median OS showed significant improvement. 7.0 months vs. 4.4 months favouring IMM-101 plus gemcitabine (HR 0.54; 95% CI, 0.33–0.87; P=0.01) when compared to gemcitabine monotherapy.

Primary Endpoint

Safety and Tolerability

IMM-101 was well tolerated in combination with gemcitabine. Grade 3 and higher treatment-related adverse events (AEs) occurred at a similar rate in both groups. Low-grade pyrexia and injection-site reactions were observed at a higher rate in the IMM-101 plus gemcitabine combination arm.

imm-101-plus-gemcitabine-medipaper-courtesy-of-cleveland-clinic

Image: courtesy of Cleveland Clinic

IMM-101 plus Gemcitabine: Worth Further Investigations?

The study had several obvious shortcomings. The study was not powered to show efficacy benefit, and metastatic subgroup consisted of 84% (n=92) of the ITT population. The second pre-defined subgroup, patients with locally advanced disease, included the remainder 18 patients (16%). Analysis of this group was severely affected by the small numbers. Finally, the authors commented the median survival in the gemcitabine control arm was lower than reported in recent studies. This may be due to the slightly older population in this study combined with overall patient selection.

Developing new therapies for pancreatic cancer is an unmet medical need. These initial, positive, results with IMM-101 plus gemcitabine deserve further evaluation in a larger, adequately powered, study.

Reference

Dalgleish, A. G., Stebbing, J., Adamson, D. J., Arif, S. S., Bidoli, P., Chang, D., . . . Mudan, S. S. (2016). Randomised, open-label, phase II study of gemcitabine with and without IMM-101 for advanced pancreatic cancer. British Journal of Cancer. doi:10.1038/bjc.2016.27

Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).

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