IMM-101 Active, Maintains QoL in Patients with Metastatic Pancreatic Cancer

Angus Dalgleish MD,

FRACP, FMEDSCI

Investigators reported a clinically meaningful extension of overall survival (OS) with IMM-101 plus gemcitabine in patients with metastatic pancreatic cancer. Findings were reported July 1 at the 17th ESMO World Gastrointestinal Conference held in Barcelona.

It was shown that the gain in OS was not accompanied by a burden of adverse events, as supported by patient-reported quality of life (QoL) scores that improved in several areas with IMM-101 treatment.

“IMM-101 is a systemic immunomodulator which has effects on innate and adaptive immune responses and which may have application across a variety of tumor types,” said Angus Dalgleish MD, FRACP, FMEDSCI, St George’s University of London, London, United Kingdom, who presented findings on behalf of the IMAGE 1 (Immune Modulation And Gemcitabine Evaluation 1) trial investigators.

IMM‑101 is a suspension of heat-killed whole cell Mycobacterium obuense (NCTC13365) in borate-buffered saline, which is administered intradermally. IMM‑101 has completed phase II clinical development in advanced pancreatic cancer but has not yet been licensed or approved.

The IMAGE 1 study enrolled 110 patients at 20 sites throughout Spain, Italy, Cypress, Ireland, and the UK. Patients with inoperable advanced pancreatic cancer and a WHO score of 0-2 were randomized 2:1 to receive 0.1 mL or 10 mg/mL of IMM‑101 by intradermal injection plus gemcitabine at 1000 mg/m² for 3 consecutive weeks in a 4-week cycle or gemcitabine alone for a maximum of 12 cycles. The primary efficacy endpoint was OS; progression free survival (PFS), safety, tolerability and QoL were also evaluated.

As previously reported at the 2015 ASCO annual meeting, IMAGE 1 met the primary endpoint; median OS in the intent to treat (ITT) population was 6.7 months receiving IMM-101/gemcitabine (n = 75) compared with 5.6 months receiving the gemcitabine (n = 35, HR = 0.68; 95% CI, 0.44-1.04; P = .075).

OS was extended to 7.0 months with IMM-01 (n=64) in patients with metastatic disease over 4.4 months in the control arm (n=28, HR = 0.54; 95% CI, 0.33-0.87; log-rank P = 0.009) — a 59% increase.

Median PFS in the ITT population was 4.1 months receiving IMM-01 and gemcitabine (n = 75) versus 2.4 months in the control arm. A stronger response was also observed in patients with metastatic disease wherein median PFS was 4.4 months versus 2.3 months in the IMM-01 and control groups, respectively (P =.001).

At the conference, results from a QoL questionnaire (QLQ) were reported that revealed clinically meaningful overall improvements in the QLQ global health and functional scale scores in least squares means changes from baseline of 5 points in the IMM-01 cohort that was maintained throughout the 45 weeks on study. Patients receiving only gemcitabine deteriorated by as much as -12 points early in the study.

QLQ-C30 functional scale scores showed improvements in emotional behavior, cognitive, physical, and social functioning that remained consistent. Patients treated with gemcitabine alone showed declines in emotional and cognitive functioning.

“These results are supportive of a longer time to deterioration in QoL for the IMM-101 plus gemcitabine treated patients,” said Dalgleish.

IMM-01-treated patients had a mean time on study of 5.52 months compared to 3.80 months with gemcitabine. This allowed IMM-01-treated patients to have greater exposure to gemcitabine; the respective treatment groups had a mean exposure to gemcitabine of 118 days versus 90.5 days.

"This is the first randomized, controlled study to assess the efficacy of combining a systemic immunomodulator with chemotherapy as first-line treatment in advanced pancreatic cancer and draws attention to the potential of such combinations as a way of improving longer term survival in this deadly disease, without precipitating toxicities," said Dalgleish.

“Overall and progression-free survival were extended with IMM-01 while QoL was maintained or improved in patients with advanced pancreatic cancer, a population of patients with a very poor prognosis.”

“Further evaluation of IMM-101 is warranted in metastatic pancreatic cancer and other cancers and combining IMM-101 with additional immunotherapies, such as checkpoint inhibitors is logical and is of interest,” he concluded.

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