Biotech Strategy Blog

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

Posts tagged ‘BMS’

Wiesbaden, Germany – Last night Bavarian Nordic dropped the unfortunate news that the phase 3 PROSPECT trial exploring the PROSTVAC vaccine in combination with GM-CSF in asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer (CRPC) was futile.

Source: Bavarian Nordic

Once you miss the overall survival (OS) endpoint, that’s it folks – there’s no other choice but to say the therapy failed, harsh though that may sound.

There are, however, a number of important points to consider from here that are worthy of further discussion.

Here, we post an analytical review and look at a number of factors that could have impacted the outcome.  It’s rarely one simple thing because the immune system is highly complex and multi-faceted.

Hopefully there will be important learnings from this study that will advance the IO and prostate cancer fields.

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Back in January this year, we posted an early look on what to expect from the evolving 1L NSCLC landscape following the controversial FDA submission of Merck’s pembrolizumab with chemotherapy. This lead to subsequent approval in May.

Checkpoint Charlie, Berlin July 2017

At that time, quite a few people were shocked and surprised that the phase 2 KEYNOTE–021 Cohort G data presented ESMO was neatly parlayed into accelerated approval in the US.

Since then, a lot has happened and now many readers are on tenterhooks as we await the next round of lung cancer trial results in the upfront setting.

First up is AstraZeneca’s MYSTIC trial exploring an IO-IO combination with durvalumab plus tremelimumab. Merck’s confirmatory trial for pembrolizumab plus chemo is also expected in the fall – will it support the accelarated approval – or not? Meanwhile, we also await Roche/Genentech’s IMpower150 study evaluating their checkpoint inhibitor, atezolizumab, in combination with chemotherapy by the year end.

These are quite different strategies with diverse endpoints so following them closely will be key to understanding what happens next.  Based on what we’ve seen in lung cancer to date, the roller coaster looks set to continue.  The C-suite shenanigans have only added to the intrigue and mystique – do they mean anything?  Who knows, but we’re focusing on the hard data i.e. science and the clinical clues that are available.

It’s all to play for and many readers wrote in asking for an update on the landscape and what to expect now that we’re much nearer to the shoes actually dropping.

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As we all wearily trawl through the huge mountain of data for ASCO 2017, what stands out – and more importantly – what matters and why?

Before we get into our in-depth coverage based on the tumour type, target and modality landscapes, I wanted to take a moment to highlight five key abstracts that stood out for me as worthy of checking out in more detail once we get to Chicago.

Interestingly, only one of them is from big Pharma!

At least one had some negatives associated with it as we’re not all happy clappy everything is great enthusiasts here at BSB.  We do try to be fair minded and objective as possible about data.

So what’s in store and why do these five matter?

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With the advent of single agent checkpoint blockade and success in melanoma, lung and urothelial carcinomas has come the realisation that the majority of patients do not respond and even some that do have a response of short duration. Immune escape and adaptive resistance are not an uncommon occurrence.

There has been much focus of late in looking at ways to address this by uncovering the relevant mechanisms underlying the biology of the disease and this is an avenue we can expect to see more research evolve. We already know that JAK1/2 upregulation and PTEN loss have lead to resistance with checkpoint blockade – what about other possible mechanisms?

Indeed, at the ASCO-SITC meeting in Orlando last week, another such target emerged and clinical evaluation is already underway, making it a worthwhile area to explore.

Here we take a look at the science and biology, as well as the emerging clinical landscape to see which companies are involved and may get a jumpstart on the combination niche.

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As we move from monotherapies to combinations in the immuno-oncology space, we start to see some intriguing ideas being explored from additional checkpoints to vaccines to neoantigens to immune agonists to oncolytic viruses. There are numerous ways to evaluate how to boost or jumpstart more immune cells upfront in the hope of seeing better efficacy.

One way to do this is to better understand the tumour microenvironment.

Wall of people at ASH16 in San Diego

If we know what’s wrong under the hood, we might be better able to make the immune system get going… more gas, faulty starter motor, dead battery, loose wire, broken fan belt? All these things and more might be a problem so you can see that diagnosing the issue up from from basic and translational work might be instructive for clinical trials.

If you don’t know what problem you’re trying to fix or repair then you might as well be throwing mud at the wall. Just as we don’t expect a car mechanic to suggest changing the battery or starter-motor without first diagnosing the issue, so understanding the tumour microenvironment in each different cancer or disease might also be a helpful strategy.

At the recent American Society of Hematology annual meeting (#ASH16), there was a fascinating sceintifc workshop that focused on this very concept – what’s going on under the hood and how do we go about fixing it?

Here we explore these ideas via an interview with a thought leader and specialist in the field. What he had to say was very interesting and candid indeed.

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San Francisco: A look at what’s new in gastric cancer (GC) from the 2017 ASCO GI meeting.

Day 1 of #GI17 is filling up…

There were several phase 3 trials presented in GC and gastro-esophageal junction (GEJ) carcinoma in both targeted therapies and immunotherapies this past weekend.

  • When we look carefully at the latest data, what do we find?
  • Where are the opportunities and challenges in this niche?

Another critical question that many observers will be interested in is…

Will BMS’s checkpoint inhibitor, nivolumab (Opdivo), overcome recent setbacks in lung cancer and make a mark in stomach cancer to challenge approved targeted therapies such as ramucirumab (Cyramza)?

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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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After some relatively quiet summer months, we have been deluged with questions and requests this month for commentary on some hot topics of late. This seems like a good time to take stock and reflect on some of most frequent ones sent in.

west-acton-tubeThe original Journal Club post slated for today will appear next week instead.

Here, we address numerous queries on the following five topics readers are interested in:

  • APHINITY trial in HER2+ adjuvant breast cancer
  • Array’s BRAF plus MEK data in metastatic melanoma
  • Kite’s interim ZUMA–1 phase 2 announcement
  • Amgen’s Kyprolis in newly diagnosed multiple myeloma
  • BMS nivolumab data in 1L lung cancer (CheckMate-026)

The last two in particular seem to be causing a lot of hand-wringing!

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Iron Men of CrosbyThis is the third in our mini-series previewing the forthcoming European Society for Medical Oncology 2016 Congress in Copenhagen (Twitter #ESMO16).

In this post we’re taking a look at what’s hot in head and neck cancer.

It’s not a cancer type we typically hear a lot about, but there’s an unmet medical need for effective new treatments.

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