Biotech Strategy Blog

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

Posts tagged ‘atezolizumab’

Exploring novel targets and modalities in advanced cancer

New waves or on the rocks

It’s not that long ago when a certain tumour type saw several waves of promising new agents emerge, quite a few of which made it past the finish line and commercial approval.

These included novel drugs, fast follow-ons, and even me-toos.

The next batch in new development pipelines were not so lucky with a series of disappointing phase 3 misses.

Then radio silence ensued.

As we take another look at this niche, there are a number of early stage agents being put through their paces – small molecule inhibitors, protein degraders, bispecifics, immunotherapies – they’re all there.

Are we going to see some new waves or will they crash and flounder on the rocks?

To find out, we delved into the latest data to determine the current status…

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WCLC23 – SCLC highlights and lowlights

Can we see the wood from the trees in ES-SCLC?

Much of the noise and attention in lung cancer is usually focused on non-small cell lung cancer (NSCLC) at cancer conferences.

While it has a greater prevalence than its more difficult to treat cousin, small-cell lung cancer (SCLC), the good news is there are now quite a few emerging novel agents and targets being evaluated in this disease.

Here we highlight and discuss some of the progress being made (or not) in the context of the broader landscape…

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Adding up the evidence

Is the emerging early stage myeloma landscape as bleak as Titan in Clydebank?

For years we have seen much of the therapeutic research in multiple myeloma concentrated on three main categories:

  • Proteasome inhibitors
  • IMiDs
  • Anti-CD38 antibodies

Then came a raft of anti- BCMA and GPRC5D targeted approaches in various forms, but what else should we be looking out for?

It turns out there’s quite a few contenders of interest – we cover some of them in our latest look at early stage compounds to watch out for…

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Chasing the alpha

It’s time to switch horses again and turn our attention to the final ASCO Plenary series of the year with another look at an anti-TIGIT trial.

After all the attention on the Genentech/Roche CITYSCAPE and SKYSCRAPER trials evaluating tiragolumab plus atezolizumab in combination of late, this time around it’s the turn of Arcus and Gilead to be in the hot seat.

In this latest instance they have data from a three arm open label randomised phase 2 study (ARC-7) exploring the Fc silent anti-TIGIT antibody domvanalimab plus zimberelimab, with and without their adenosine axis therapy, etrumadenant, both compared with the anti-PD-1 antibody alone in 1L NSCLC.

The results turned out to be rather controversial for a number of reasons, so let’s take a deeper look at what can be learned and why it matters…

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Sorting out confusion, confliction, and confounding results in clear cell RCC

Which direction should we go in early stage RCC?

The battle for early stage RCC at the European Society of Medical Oncology (ESMO) is turning out to be quite a humdinger this year with quite a few unexpected surprises in store given the variety of trials with different agents and combinations generating a disparate variety of readouts.

Why is this and what can we do/learn from the findings?

In this post, we offer an in-depth discussion and commentary from various GU and IO experts…

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New directions in small cell lung cancer

Linie 30 Florisdorf, Vienna

With all the frequent attention on lung cancer of late – mostly on the most common form, non-small cell lung cancer – it’s easy to forget small cell lung cancer (SCLC) in the rush to highlight new developments.

It’s time to talk turkey about old and new agents in the quest to improve outcomes for people with this dismal disease.

The good news is there are also a raft of scientific developments emerging, which may potentially help us better identify discrete subsets and enable the matching of appropriate regimens to the underlying biology.

At the World Conference in Lung Cancer this week in Vienna we’ve been following the numerous trials (and tribulations!) of progress in this niche, with a look at several key readouts through the lens of a thoracic lung cancer specialist.

What does he have to say and where are things heading next for the field?

To find out more, check out the interview below…

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What do the Konami code and targeting KRAS have in common?

It seems astonishing to realise only a couple of years ago KRAS was considered undruggable intractable and here we are, not only with one drug approved, another filed and veritable long list of fast followers, but a whole ecosystem of different agents vying for a place at the table.

The wonderful news is we are starting to think more broadly about life beyond G12C mutations, not only with different combinatorial approaches, but also also in the context of how to tackle other related mutations as well.

Here, we wanted to explore the evolving universe more broadly and assess criticality as well as applicability – which agents might shine tomorrow if clinical data turn out positive?  The simple answer is more than you know.

So just who are the rising stars in this emerging landscape and what can we learn about them?

Be warned in advance – this is one of our longest and most comprehensive reviews on BSB with over 30 compounds highlighted in different guises, so grab a cup of Joe and be prepared to come with an open mind…

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An alternative perspective on TIGIT

We’ve written a lot on TIGIT as a cancer target going back to 2015 (see examples here) as we have followed the trials and tribulations of numerous developments in this niche longitudinally.

I’ve often wondered how people would have viewed results from anti-CTLA4 trials had anti-PD(L)1 therapies came first and not the other way around.  You just imagine the disappointment this might have induced given the way things panned out!

Not all anti-PD(L)1 agents have consistently demonstrated similar results – some have succeeded where others failed. Whether this was due to differences in trial designs, different patient populations, or other factors is often something of a mystery since there is still much we don’t know – the unknown unknowns – and how they can impact performance. If they are not accounted for in the baseline characteristics then differences in outcomes might well unwittingly be impacted from the get-go.

It was always going to be tough to add in another immunotherapy agent and shift the survival curves up and to the right, thereby impacting outcomes even further.

Should we be considering the recent top line tiragolumab readouts an indication of failed trials or something else?

In our latest analysis, we consider a number of pertinent factors and discuss how they can impact performance…

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Are there challenging times ahead for KRAS inhibitor combinations?

One of the biggest challenges in any cancer combination trial is optimising the therapeutic window.  This is especially the case when there are known overlapping toxicities.  We’ve seen this happen many times in the past with targeted therapies where promising approaches from preclinical studies are subsequently abandoned in phase 1 trials because the toxicities can limit the dose that can be achieved, thereby impacting the response rates or outcomes in a negative fashion.

Immunotherapy trials also present additional challenges to be addressed in the form of immune-related adverse events, which might be potentiated or reactivated by subsequent targeted therapies, not all of which can be predicted from preclinical experiments.

Several KRAS inhibitors have already been abandoned in phase 1 development due to unexpected systemic events surfacing, as have various IO-IO or IO-targeted therapy combinations.

What happens when the KRAS and IO worlds collide?  Are there toxicities which might scupper future promising combinations and send us all back to the drawing board again?  Does the lion roar or whimper?

In our latest post, we explore the ins and outs of one such emerging controversy, including some thought leader persectives…

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The battle for early stage lung cancer continues apace

Sunrise or sunset in NSCLC?

Is it time for the dawn of a new era in early stage lung cancer or are the initial trials more of a sunset on future opportunities due to more modest than expected data?

One challenge with interim readouts in the adjuvant setting is they are a reflection of the top part of a very long survival curve, so large differences are rarely apparent at this stage when the timeline might be going out 10-12 years.  This is especially true for IO studies where these agents have consistently shown to impact landmark survival and the long tail of the Kaplan-Meier curves.

While previous studies more than a decade ago have shown some benefit for chemotherapy over observation in terms of overall survival, we have no other reference points in lung cancer, unlike breast and colon trials where some targeted therapies have seen success in the adjuvant setting.

This is very much a case then of ‘once more unto the breach, dear friends,’ as Shakespeare would say.

We have already seen approvals for immunotherapies in both neoadjuvant (nivolumab) and adjuvant (durvalumab and atezolizumab) stages of lung cancer, now it’s time to put pembrolizumab in the spotlight…

Are they building a cathedral or a brick wall?

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