Biotech Strategy Blog

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

Posts tagged ‘ASCO20’

The past year has seen hype and hope over targeting KRAS mutant cancers and many challenges still remain to be addressed. We’ve seen the emergence of selective G12C inhibitors, as well as others targeting SOS1:RAS upstream and even related pathways to address cross-talk such as SHP2 and ULK1, for example. The oncology R&D ecosystem is beginning to motor again as new competitors start entering the niche.

Riding the KRAS wave

To put things into broader perspective, however, despite all the positive news in lung cancer, consider the colorectal carcinoma data was less impressive than lung because of more complex, heterogeneous disease.

Meanwhile, Lilly recently announced the discontinuation of their selective G12C inhibitor, LY3499446, due to adverse toxicity, so clearly it is not all going to be plain sailing in this landscape!

Let’s also not forget the G12C mutation is not the only viable target in this context. People with advanced lung cancer can also present with one or more of several co-occurring mutations such as the serine/threonine kinase 11 gene (STK11) and kelch like ECH associated protein 1 gene (KEAP1), for example.

Unfortunately those presenting with both STK11 and KEAP1 mutations – independent of KRAS status – often have a poorer prognosis and there remains an unmet medical need for effective new treatments.

In this fourth postcard in our summer mini-series on the potential of immunometabolism for cancer immunotherapy, we’re taking a look at a novel way to target KRAS mutant lung cancer and, in particular, those with an STK11 and KEAP1 mutation who tend to do poorly on current therapies.

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Continuing our latest cell therapy mini-series, this time around we focus on a novel and creative approach to CAR-T cell therapy, which is quite different from what we have described before with other companies in this niche.

One emerging trend is the development of bi- and even tri- specific approaches designed to target multiple aberrations in the cancer cells, but what’s the best way to achieve this? Suppose we ditch the core dogma and try another way of doing things?

The entirely new concept making the splash is also coming from an emerging young biotech company few readers will likely have heard of, yet what they are doing reminds me we can borrow from the past and paraphrase a watch ad from the 1980’s for elegant and simple timepieces – some day all CAR-Ts will be made this way.

The secret sauce this time around isn’t quartz, however, but something completely different…

To learn more from our oncology analysis and get a heads up on insights and commentary on an emerging novel and creative CAR T cell therapy approach, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Do any of the early trials in advanced cancers aspire to be great?

Not in Chicago – Of relevance to the ongoing ASCO20 coverage, in the Preview series this year, two of the companies we highlighted going into the meeting (Innovent and Alphamab) both announced deals this week with Roche and Sanofi, respectively – talk about highlighting hot topics ahead of time 😉

After last week’s look at winners and losers in hematologic malignancies, this time around we now turn our attention to explore what’s happening on the new product development front regarding solid tumours.  In this review, we critique some of the trials presented and put them in broader context.

As always, there are both some important learnings we can glean as well as some, well, head/desk moments to contemplate…

To learn more from our oncology analysis and get a heads up on insights and commentary emerging from the ASCO meeting, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Not in Chicago: A hallmark of the annual meeting of the American Society of Clinical Oncology (ASCO) is “practice changing” clinical trial data often featured in the plenary session.

This year one of the noteworthy phase 3 trials presented at the meeting (link to ASCO20 Abstract LBA5), was the AstraZeneca sponsored “ADAURA” trial for osimertinib as adjuvant therapy in patients with stage 1B-IIIA EGFR mutation-positive NSCLC after complete tumor resection.

We’ve been following the clinical development of osimertinib since the initial presentation of the phase 1 data in 2013 (link).

Source: ASCO20 Press Briefing by Dr Roy Herbst

At first glance it’s hard not to be wowed by the separation of the disease-free survival (DFS) curves in ADAURA, which show a benefit for patients who received the EGFR inhibitor osimertinib compared to those who received placebo. A 0.17 hazard ratio is certainly not something we see every day.

Indeed, if you were in the media and listened to Dr Herbst on the #ASCO20 press briefing last week – to use a “Britishism” – you would have thought this trial was “the best thing since sliced bread.”  The data monitoring committee recommended unblinding the study early.

Dr Ross Camidge Colorado

D Ross Camidge, MD PhD

Anyone leaving the story there and doing a superficial report about this data is, however, doing a disservice to their readers. The US academic lung cancer community are not all singing Handel’s Hallelujah chorus for the ADAURA trial and in this post, we take a critical look at why this might be the case.

For good measure, we interviewed a global thought leader who was prepared to offer some candid expert commentary.

Dr Ross Camidge is Professor of Medicine/Oncology and holds the Joyce Zeff Chair in Lung Cancer Research at the University of Colorado school of medicine. He kindly spoke to BSB and shared his perspective on adjuvant therapy in EGFR mutant lung cancer.

Dr Camidge characterized the disease-free survival in the ADAURA trial as a potential false dawn and told BSB:

“I do not believe the data should be practice changing or at least not yet. I think when you show there is an overall survival benefit then it will be practice changing…

So far there is no reason to suggest that disease free survival is going to translate into an overall survival advantage as it has not in any other comparable targeted therapy trial in EGFR mutant lung cancer. If this trial is the exception though, it will certainly not be of the same magnitude as the DFS benefit. However, the real unanswered questions are who needs this drug in this setting and if they need it, who can stop it safely and when.”

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It’s time for another landscape review of a particular class of drugs in early development.

Here we take an in-depth look at the emerging SERD landscape in ER+ metastatic breast cancer. There’s a lot going on the ER+HER2- niche these days after a bit of a lull once we saw the CDK4/6 inhibitors approved so it’s a good opportunity for some extended colour commentary on what could become a hot area in oncology over the next couple of years.

Overcoming or delaying the onset of therapeutic resistance is going to be important, but how do we go about achieving this?

Historically we have seen some success in inhibiting the activity of the estrogen receptor (ER) as a driver of oncogenic activity, but what if we could degrade the aberrant protein instead? Would this approach yield some further benefits for people with advanced breast cancer?

There are quite a few companies, big and small, involved in this space so there’s still much to play for, especially in terms of figuring out what the ideal drug should look like and which combinations might be most useful. We also highlight key upcoming conference presentations to watch out for – hint: there’s quite a lot of them!

To learn more from our oncology analysis and get a heads up on insights and commentary emerging from the ASCO and second AACR virtual meetings, subscribers can log-in or you can click to gain access to BSB Premium Content.

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Time for some additional colour commentary!

There has been some incredibly intense interest surrounding TIGIT as a new therapeutic target in oncology of late, to the point where some observers have been wildly claiming this is the new universal checkpoint everyone has been waiting for.

But is it?

It’s early days yet with little data presented from people with cancer, so at this point it could well be a bit of a stretch to find another anti-PD–1/PD-L1 equivalent, but this doesn’t mean there isn’t utility in seeing clinical activity in some tumour types, far from it.

In our latest post, we take a look at what’s coming up in the TIGIT niche, along with an interview from a company active in this niche.

What do the company have to say and how do they see this panning out?

To learn more from our oncology analysis and get a heads up on insights and commentary on a new checkpoint target called TIGIT subscribers can log-in or you can click to gain access to BSB Premium Content.

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