Biotech Strategy Blog

Commentary on Science, Innovation & New Products with a focus on Oncology, Hematology & Cancer Immunotherapy

Posts tagged ‘lirilumab’

Head and Neck cancer – or to be more precise – squamous cell carcinoma of the head and neck (SCCHN) has joined the checkpoint inhibitor club with two FDA approvals this year. National Harbor Maryland

Firstly, we saw the accelerated approval of pembrolizumab (Merck) based on objective response rate on August 5, 2016 for patients with recurrent or metastatic head and neck squamous cell carcinoma (SCCHN) that has continued to progress despite standard-of-care treatment with chemotherapy.

It’s a dismal disease with a generally poor prognosis in advanced patients once initial therapy fails.

While some patients do benefit with anti-PD–1 checkpoint therapy, the overall response rate in the KEYNOTE–012 trial of 174 patients was pretty low, i.e. 16%. In other words, the majority of patients do not respond or receive any clinical benefit.

Secondly, last week on November 10 nivolumab (BMS) was approved by the FDA based on the phase 3 CheckMate–141 data presented at ASCO earlier this year. The data was published in the New England Journal of Medicine to coincide with the FDA approval.

There were no statistically significant differences between the two arms for median PFS (2.0 months with nivolumab versus 2.3 months with standard therapy, HR for disease progression or death, 0.89; P=0.32) or ORR (13.3% vs. 5.8%) for nivolumab versus investigator’s choice, respectively. There was, however, a clear benefit in favour of nivolumab in median overall survival (7.5 months in the nivolumab group versus 5.1 months in the control group; HR 0.70; P=0.01).

This effect on patient outcome is a classic pattern for cancer immunotherapy with checkpoint blockade. Response rate and PFS are measurements that are very relevant to chemotherapy, but they are not as relevant to cancer immunotherapies where what is impacted more noticeably is overall survival and the long tail of the curve.

With two approved anti-PD–1 monotherapies in SCCHN, the next challenge has now become how can we improve on monotherapy by boosting the number of PRs to CRs potentially improving long term outcomes and/or turn non-responders into responders? This is the stage we are at in many tumour types now.

Combination approaches are believed to be the way forward, which is why we anticipated with great interest the lirilumab plus nivolumab head & neck combination data presented this past weekend at the 2016 Society for Immunotherapy of Cancer (SITC) meeting at National Harbor, MD. The presentation is available for download on the Innate Pharma website. The data raises numerous questions and scenarios that can be considered…

  • Are the data exciting, encouraging or disappointing?
  • Are the results enough to give confidence if a phase 3 trial with the combination were to follow?
To address these questions and other critical issues – including red and green flags – we took a deep dive into the data in the context of scientific facts and explored the landscape carefully.

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Part 3 of our series on Gems from the Poster Halls at ESMO continues with a look at another four important combination studies that may be of keen interest to readers.

These include both targeted therapies as well as immunotherapies.

Some of the posters I was originally keen to write about turned out a little unexpectedly with some issues to address i.e. lack of efficacy or unwanted toxicities based on the dosing schedule used and may require tweaking of the dosing, schedule or trial design. Others will unfortunately be destined for dog drug heaven unless a new tumour type offers more promise. Such is the R&D roller coaster that is oncology – sometimes we forget that more compounds fail than make it market.

The good news is that there were plenty of promising approaches that are worthy of writing up and discussing. In the third part of our poster mini-series, we take another deeper dive with a careful look at some new data in Copenhagen.

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Eric Vivier, DVM PhD (@EricVivier1) is a leading French immunologist whose research has focused on understanding the innate immune system, and in particular, the role natural killer (NK) cells and innate lymphoid cells (ILC) play.

prof-eric-vivier

He is Director of the Centre d’Immunologie de Marseille-Luminy (CIML) and a Professor of Immunology at Aix-Marseille University.

In addition to his academic work, he also co-founded the biotech company Innate Pharma back in 1999. Through the company, he is actively involved in the translation of basic research into new cancer immunotherapy treatments.

New clinical data is eagerly expected for one of these, a first-in-class monoclonal antibody against KIR (lirilumab). It is in phase 2 clinical trials with Innate Pharma and Bristol Myers Squibb.

At the recent scientific meeting to celebrate 40 years of CIML (#CIML40), Professor Vivier kindly spoke to BSB about his research into innate immunity and the Marseille Immunopôle, for which he is also a co-founder.

It is an immunology cluster that brings together academic/clinical research with innovative biotech companies looking to bring new drugs and diagnostics to market.

This is the second post in our mini-series from the Marseille Immunopôle and CIML40. It also sets the scene for forthcoming posts on targeting the innate immune system, something you can expect to hear a lot more about in cancer immunotherapy.

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In the past, I’ve sometimes been accused of being a bit of an immunotherapy bear for my dislike of cancer vaccines as a single agent therapy in advanced disease where the tumour burden is very high. That particular field has undoubtedly been a huge graveyard for many companies, much in the same way that metastatic melanoma was, until novel therapeutics and immunotherapeutics emerged to push through the envelope.

To be clear, I am though, a big fan of targeted immunotherapies such as checkpoint inhibitors and chimeric antigen receptor (CAR) T cell therapies, which have been very much to the forefront in immuno-oncology over the last two years and rightly so, with some initial trials showing some very promising results.

Both of those approaches are squarely part of the adaptive immune system and seek, in different ways, to retrain the bodies immune system to fight the tumour. More recently, the innate immune system has seen new advances as reearchers moved beyond simple vaccines to develop more thoughtful and innovative approaches that seek to outwit the very masking the cancer is trying to fool the immune system with. It’s no less exciting, just a different way of looking at the science and improving out understanding of the biology of the many diseases that cancer makes up.

In this AACR preview, I take a broad look at some innovative and novel scientific approaches, including targeting anti-CD47 and SIRPα (Stanford and Stem Cell Therapeutics), KIR and MICA (Innate Pharma) and neutrophils (Biothera).

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In the second part of our mini-series on immuno-oncology, I thought it would be a nice idea to share a recent interview conducted with one of Roche/Genentech’s leading researchers in this field.  I was particularly interested in their approach because while BMS and Merck have clearly focused on anti-PD-1, Roche and Genentech have effectively zigged with their development of an anti-PD-L1 inhibitor.  Does this matter?

Here, we explore the general background to this approach and, in particular, where the company are going with their anti-PD-L1 inhibitor, MPDL3280A.

Topics discussed:

anti-PD-L1, anti-PD-1, anti-CTLA-4, checkpoint point inhibitors, T cells, biomarkers.

Drugs mentioned:

MPDL3280A, nivolumab, MK-3475, ipilimumab (Yervoy), lirilumab, BMS-986016 (anti-LAG3), bevacizumab (Avastin), erlotinib (Tarceva), vemurafenib (Zelboraf), cobimetinib.

If you are interested in more background on how the PD-1 and PD-L1 inhibitors work, you can check out the mechanism of action (MOA) in our video preview from ASCO last year, which explains this in fairly simple terms.

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Beyond the noise of the exciting the data in CAR-T cells, CLL, NHL and multiple myeloma, one of my favourite pastimes at cancer conferences is to look out for up-and-coming gems in the poster halls.

By this I mean interesting novel targets or very active agents in the pipeline.

One of the most eagerly awaited targets on my list was the Killer Immunoglobulin-like Receptor (KIR). It may be a key part of overcoming lymphoma resistance and inducing cell death. If you don’t kill the cancer cells, you likely won’t see remissions occurring.

Companies mentioned: Innate Pharma, BMS, Roche

Products mentioned: IPH2101, IPH2102 (lirilumab), ipilimumab, rituximab, obinutuzumab, anti-PD-1, anti-PD-L1

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