Biotech Strategy Blog

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

Posts tagged ‘nivolumab’

With so much data to cover recently, we haven’t have time for a perennial favourite, the monthly mailbag to answer BSB reader Q&A on hot oncology topics.

October has brought out quite a lot of controversy to consider, most of it happening in the last week!

Here, we consider questions on Immune Design’s phase 3 trial with their NY-ESO-1 vaccine, CMB305, which attracted both a lot of market attention and also questions from readers.

We also review a bunch of questions relating to 1L NSCLC and the upcoming readouts.  This niche is probably potentially one of the most competitive spaces in oncology R&D at present and readers seem almost insatiable for information on this topic.

It is quite a turnaround considering the last decade of numerous failed trials or even non-inferiority studies that were being conducted.

Like many readers, I can well remember sitting in freezing cold, half empty halls wondering if the latest chemo or targeted therapy doublet was going to offer a mere 2-3 months improvement in PFS and no OS benefit or not.  It was that binary and also depressing.

With the possibilities offered by immune checkpoint blockade, in a short space of time 1L NSCLC has gone from graveyard to uber intense with several companies vying to demonstrate improvements in overall survival by 6 months or more.

There’s a lot more to come here and not all of the lung trials will be positive – that’s expecting too much against the game of chance.  Here, we look at numerous factors that could make a difference, both positive and negative.

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As we demonstrated in the recent Novel Targets podcast that opened Season 3, one topic that is a key focus for many in the IO space is addressing mechanisms of immune escape and acquired resistance to single agent treatment with immunotherapy.

We’ve seen several oncogenic escape mechanisms reported, included activation of the JAK/STAT pathways in some patients and loss of existing immunity when the tumour suddenly becomes cold or an immune dessert.

The good news is that there are a number of ideas that can be pursued, including activating the innate immune system in various combinations.

As we see more companies invest in the innate immunity space in order to have a rational partner with which to combine with their checkpoint inhibitor, it will be important to maintain focus on trial designs and synergistic mechanism of actions to improve efficacy while reducing the potential for overlapping or severe toxicities.

Here’s one intriguing and promising new approach that caught our eye this month that is worthy of researching and following over time…

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Greetings from continental Europe!

ESMO Madrid Conference Center

We have a LOT of data to discuss today from ESMO and have also included an interview with one expert that was conducted under embargo on an important topic.

Of course, the usual in-depth analyses on new targets and early compounds in development will duly follow in the post-meeting output, but there’s plenty of practice changing data to consider and also some results that may trigger alternative thinking from where we are now.

We also received questions from BSB readers on certain trials and some of these are answered in today’s update on the road…

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It really doesn’t feel like a year since we were at ESMO in Copenhagen, in what was probably the most exciting meeting of the year in many ways.

Packed audience!

With the ASCO abstract deadline being in Jan/Feb, ESMO offers a great opportunity for companies to have another major slot in the calendar to present ground breaking data. In some ways, having positive data at a European meeting can actually amplify positive studies that might otherwise get lost in the noise at ASCO, which is almost becoming too big.

So what’s in store now that the meeting is upon us?

There are some large and small trials with important data on the first two days that bear thinking about and further discussion.

Here’s our take on the first batch of readouts, including some surprises…

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Madrid city center

Greetings from Vienna, Austria!  Fresh off a red eye… we’re en route to one European cancer conference in Germany, while writing about another one in Madrid.

This latest preview looks at some of the key IO studies that are either intriguing or have potentially interesting results that BSB readers have written in asking us about.

There are some targeted therapies thrown in too for good measure too, as there are some IO-targeted combos to look at, as well as IO-IO approaches.

What I want to accomplish in this latest preview is point out some elements of what we call ‘interestingness’ where people should be watch or wary of either jumping to conclusions or making comparisons across trials and arriving at assumptions that may not turn out to be valid. My best advice here is to always be sceptical and assume there’s no concordance and that way you won’t be caught unawares.  It’s easier said than done, though.

Indeed there were so many questions about ESMO that we needed two preview posts to cover many of the questions we received.

Part 2 should roll out tomorrow, wifi on the road permitting – stay tuned for more on ESMO17.

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In our ESMO 2017 Preview series so far we covered our Top 5 immuno-oncology and targeted therapy abstracts to watch out for (the latter has been updated since it first posted so do check it out).

Now it’s time to turn to something completely different.

Castle Manzanares el Real, Madrid

Here we look at hepatocellular carcinoma (HCC), including Blueprint Medicines FGFR4 molecule, BLU–554.

We first covered Blueprint back in February this year with a particular focus on GIST.  Quite a bit has changed since then, so it’s a good time for an update, especially in HCC now that they have data in Madrid.

In the context of the HCC landscape, what’s changing in this niche, what should our expectations be, and how is this market evolving since our last update?

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There’s been another disturbance in the force – as luck would have it, after mentioning renal cell carcinoma (RCC) in yesterday’s post, BMS subsequently put out a press release on the CheckMate–214 study exploring the combination of nivolumab plus ipilimumab in the previously untreated metastatic setting.

The results to date were mixed, so what does this mean and what’s impacted by the findings?

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Berlin: Checkpoint Charlie

With a series of inconsistent results involving phase 3 trials involving checkpoint antibody therapy, even in similar indications, it’s time to get down and dirty and look at some of the factors that might be influencing the outcomes since three of the five approved anti-PD(L)1 products have now been similarly affected.

It’s an interesting and intriguing conundrum, to be sure…

Instead of obeying traffic rules, with immune checkpoints maybe we need to consider following immunology rules instead 🙂

The potential hidden answers, however, might be surprising to some readers.

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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 start to see early readouts from new IO combos and also new trials emerge to begin enrolling patients, it’s going to be intriguing to see how the new cancer immunotherapy landscape evolves.

ASCO17

Some of these trials will be random in that the drugs are what the company has, others will be based on existing or new collaborations, while others will be based on rationally based science… not all will be successful, though.

Of course, it’s easy for all of us to be an armchair critic and grumble about the flaws, the problems, and even the weaknesses in clinical trials, but what about rational approaches that attempt to scientifically address the acquired resistance that develops on montherapies?

Here’s one approach I really like – we’ve written about the underlying biology behind it previously, but what about the clinical trials, and what does the company evaluating the combos think?

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