IMM-101 Trials

Immodulon is committed to a rigorous programme of clinical trials and pre-clinical studies for its lead product, IMM‑101, in the treatment of various forms of cancer, in combination with other anti-cancer treatments. Clinical studies indicate that IMM‑101 is well tolerated and has a potentially transformational impact on survival rates for cancer.

IMM‑101 Phase I

In 2010, IMM‑101 was evaluated in a Phase I trial (a trial which tests what a drug does to a patient’s body and how well it is tolerated), enrolling 18 patients with advanced melanoma where the disease had spread to the patient’s other organs. Sadly, historically only approximately 10% of patients survive 5 years with this condition. The unexpected result of an extension to Phase 1 trial, however, was that six patients receiving IMM‑101 are still alive more than five years later.

This is a 5-year survival rate of 33% and is exciting because it is comparable with leading approved immunotherapy treatments, but without adding to toxicity levels in the body and has the potential to be used in combination with other treatments, further enhancing their impact on patient outcomes.

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Survival of patients with metastatic melanoma – view larger image

The initial paper on the Phase I study was published in the Annals of Oncology (Oxford Journals) 2011: Stebbing J. et al. An intra-patient placebo-controlled phase I trial to evaluate the safety and tolerability of intradermal IMM‑101 in melanoma which describes the initial safety and tolerability data.

These long term follow up results were presented at the international European Society of Medical Oncology (ESMO) meeting in Lausanne in November 2015 and some patients are still in a follow up study.

IMM‑101 Phase II

In 2013, IMAGE-1, a Phase II proof-of-concept study of 110 patients with locally advanced or metastatic pancreatic cancer was initiated. Patients were given the chemotherapy drug gemcitabine with and without IMM‑101. The study was designed to provide indicative rather than definitive efficacy results, but exceeded expectations by providing promising overall survival results and durable responses in all prospectively defined populations as well as a favourable safety profile.

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Kaplan Meier (KM) survival curves for the ITT population with metastatic disease.

The graph shows the Kaplan Meier (KM) survival curves for the Intention-to-Treat (ITT) population with metastatic disease where an increase in median survival of 2.6 months corresponds to a 59% increase in survival for patients receiving IMM‑101 + gemcitabine compared to gemcitabine alone. Equally importantly, the continued separation of the KM curves to 24 months and the survival outcomes at 12, 18 and 24 months indicate a long lasting response for some patients with this devastating disease. Safety analysis indicated no apparently additional burden of side-effects in adding IMM‑101 to gemcitabine. IMM‑101 is gentle to the body and does not add a further burden on the patient’s health and quality of life. Side effects were limited to swelling and itching where the injection is administered, similar to a BCG injection.

For the full paper published in the British Journal of Cancer (Nature Journals) 2016: Dalgleish A. et al. Randomised, open-label, phase II study of Gemcitabine with and without IMM‑101 for advanced pancreatic cancer. The IMAGE-1 Trial (Immune Modulation and Gemcitabine Evaluation-1).

IMM-101 future trials

Immodulon is in the process of setting up two trials, a broad entry Phase II study (MODULATE) to begin in early 2017, and a global Phase III trial (IMAGE-2) to start in Q1 2018.

MODULATE is an exploratory study and will test IMM‑101 in combination with a wide range of other treatments (standards of care) to show IMM‑101’s application as a foundation for cancer treatment across a broad range of cancers. Immodulon will be working with key oncologists and cancer centres in the UK and abroad to recruit patients.

The study will take up to three years to complete and results will be published as papers at key stages in the study’s duration, when results become available. The trial will be led by Professor David Cunningham, Consultant Medical Oncologist and Director of Clinical Research and Development at The Royal Marsden NHS Foundation Trust in London.

IMAGE-2 is a large Phase III clinical trial of IMM‑101 in the treatment of metastatic pancreatic cancer in combination with gemcitabine and is designed to confirm the very encouraging results observed in IMAGE-1 (ref BJC paper) so as to bring IMM‑101 to market both in Europe and the US. Immodulon is designing the trial in consultation with Key Opinion Leaders, after which, recruitment will begin through partner clinics and centres in several geographical locations.

Additional exploratory clinical studies will be implemented as funding becomes available to ensure that additional potential routes to registration and launch are rapidly evaluated. Potentially Immodulon will support additional studies to be run in parallel with the MODULATE and/or Phase 3 studies, to evaluate the use of IMM‑101 in:

  • - melanoma patients in combination with available immune therapies such as checkpoint inhibitors (anti-PD-1 or anti-CTLA-4)
  • - refractory bladder cancer in patients who fail intravesical BCG therapy
  • - head and neck cancer in association with EGFR-targeting antibodies
  • - other diseases which, like pancreatic cancer, have not shown a positive response to immunotherapy e.g., second line sarcoma and cholangiocarcinoma
  • - biomarker studies to assess the effect of IMM-101 in immunologically “cold” tumours
  • - ultra-orphan (extremely rare) diseases, such as Erdheim Chester Disease and IL-12 deficiency
  • - identification of predictive biomarkers that will help to determine in which patients IMM‑101 works best. These biomarkers are unlikely to require an expensive diagnostic kit which often adds substantially to the overall treatment cost