Biotech Strategy Blog

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

Posts tagged ‘non-small cell lung cancer’

At ESMO IO last Fall, Genentech/Roche were first past the post in 1L non-small cell lung cancer (NSCLC) with data from their phase 3 study in non-squamous patients evaluating the combination of chemotherapy and bevacizumab plus atezolizumab versus chemotherapy alone.

The 1L NSCLC race continues apace…

Since then, there has been much anticipatory excitement for BMS and Merck’s phase 3 trials, CheckMate-227 and KEYNOTE189, respectively.  These data will be now presented at the annual meeting of AACR in Chicago next month.

In the meantime, there are also the overall survival data expected soon from AstraZeneca’s MYSTIC trial – will it be positive despite a PFS miss?

Later this year, the company have another study (NEPTUNE) result expected that explores the combination of durvalumab plus tremelimumab versus platinum-based standard chemotherapy in first line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type advanced or metastatic NSCLC.  This has been a controversial area for IO studies to date and the story here may well be more subtle and complex than many realise.

Next year we can also expect to see more readouts from Pfizer/EMD Serono’s JAVELIN LUNG 100 (avelumab) in both squamous and non-squamous histologies, while AstraZeneca’s POSEIDON study is in squamous patients only.

Just this week, Genentech again announced their phase 3 squamous NSCLC trial readout with positive PFS in favour of the combination of chemotherapy plus atezolizumab versus chemotherapy alone.  The BMS CheckMate-227 study included both sets of histologies and no details were provided in the announcement, so hopefully this data will be available at AACR.

In Pharmaland we hear much noise around First-in-Class and Best-in-Class claims but, ultimately, it will all come down to data.  In oncology, it always does.

In our latest review post, we take a look at both squamous and non-squamous settings and what we learn from the latest available information.  Surprisingly, it’s quite a lot and there are important nuances to consider as well…

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Challenges and Opportunities in the evolving 1L NSCLC Landscape

Rolling English Landscape in Devon

Following a series of events – from BMS’s failure with nivolumab monotherapy… to Merck’s sudden announcement to file their combination of pembrolizumab plus chemotherapy… to AstraZeneca’s delay of the MYSTIC trial exploring durvalumab plus tremelimumab this week, there’s never a dull moment in lung cancer!

So can we expect some more surprises in store in 1L NSCLC?

I say yes we can!  

The big questions are what are they and what impact will they have?

2017 is ironically, the year of the Rooster – so who’s going to crow loudly at dawn and who is going to get strangled in the process?

In the world of cancer research it is unlikely that everything wins or is successful, so figuring out the early signs and hints is an important part of the process.

One thing I learned early in this business is that it pays for companies to be humble, flexible and open minded rather than arrogant and dogmatic in their thinking… otherwise you can easily be blindsided.

There were a few examples of that in oncology R&D last year, a repeat could very well follow in 2017 for the unwary.

Here we look at 1L NSCLC in the context of multiple phase 3 trials that are slated to read out… from AstraZeneca, BMS, Merck and Genentech.

If you want to know what the potential impact of these events are on the landscape, including what we can expect from MYSTIC, CheckMate-227 and several others, then this is the post for you because some surprises are likely in store.

We cut through the chase to explain the what and the why in clear simple language.

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Yesterday saw the FDA approval of atezolizumab (Tecentriq) for the second-line treatment of metastatic non-small cell lung cancer (NSCLC) (link to company press release).  According to Genentech:

“This approval is based on results from the randomized Phase III OAK and Phase II POPLAR studies. The largest study, OAK, showed that TECENTRIQ helped people in the overall study population live a median of 13.8 months, 4.2 months longer than those treated with docetaxel chemotherapy (median overall survival [OS]: 13.8 vs. 9.6 months; HR = 0.74, 95% CI: 0.63, 0.87). The study enrolled people regardless of their PD-L1 status and included both squamous and non-squamous disease types.”

The FDA approval is largely a broad one in 2L and 3L across PD-L1 expression and histologies [Link]:

“TECENTRIQ is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving TECENTRIQ.”

The approval was widely expected in light of the Phase III OAK trial data presented in the Presidential Symposium at ESMO16 meeting in Copenhagen.

Sign adjacent to #ESMO16 in Copenhagen

Sign adjacent to #ESMO16 in Copenhagen

Imagine hearing live about positive first-line data with pembrolizumab, with and without chemotherapy, negative data from nivolumab in the same setting, the 2L data for atezolizumab and two discussants drilling into both the data and broader impact of these studies to a jam packed audience that even included thought leaders from other tumour types who were also eager to hear the news. To say the atmosphere was electric would be a rather British understatement here.

We previously covered our initial impressions from that session [Link], but we also had the pleasure and privilege of interviewing a leading US thought leader in the lung cancer space after the session to garner his impressions of the data and also some perspectives on the key issues that the field is facing.

The pembro plus chemo data is already providing some controversy amongst various protagonists given there are a number of similar combination trials expected to read out over the next year to 18 months, plus much anticipation from analysts regarding the ditching of chemo for IO combos such as anti-PD–1 plus anti-CTLA–4 (BMS and AstraZeneca have keen stakes here), but what do thought leaders really think of that concept? Is that the slam dunk that many analysts seem to think it is?

This, my friends, is where things start to get a lot more complicated, akin to 3D chess in Star Trek.

What is happening now in advanced NSCLC is not how the market will look in a year or two. In many ways, the rate of approvals are outstripping the pace of science right now, but once the low hanging fruit is gone, competition will need to evolve in much more sophisticated and elegant levels.

With these questions in mind, we have a double header for you today – you can read on to find out more details from our latest though leader interview, supported by some insightful perspectives from a medical oncologist who treats lung cancer patients in private practice. Today’s post therefore covers some wide ranging discussions across the key issues in advanced NSCLC and it’s future direction.

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Lung cancer, along with metastatic melanoma, has been very much to the forefront of attention in cancer immunotherapies with both nivolumab (Opdivo) and pembrolizumab (Keytruda) garnering approval as monotherapy from the FDA in second line treatment of NSCLC. A third molecule, atezolizumab (Tecentriq) has also been submitted to the authorities for this indication and a decision is expected soon.

Morgan Grafitti Wall

Street art in the Chicago West Loop

While no one is in any doubt that the response rates with monotherapy are low (in the 20% range) and the majority of people do not respond, the important thing so far is that when they do, they appear to be very durable responses. People are living longer, much longer than the 2–3 months of incremental improvement we are used to seeing with chemotherapy or targeted therapies.

The race is now on to see how we can improve things for the 80% of people with lung cancer who don’t respond to single agent therapy:

  • What can we do to help them?
  • Which combinations look more encouraging?
  • Should we treat beyond progression?

To answer these questions, we interviewed Dr Stephen Liu and discussed his views on some of the cancer immunotherapy combination studies presented at ASCO last week.

Dr Stephen Liu

Dr Stephen Liu at ASCO 2016

Dr Liu is a lung cancer expert at the Lombardi Cancer Centre at Georgetown University, and is actively involved in numerous clinical trials, particularly in Developmental Therapeutics.

Georgetown’s founding principle is Cura Personalis, which translates as care of the whole person. It “suggests individualized attention to the needs of others, distinct respect for unique circumstances and concerns, and an appropriate appreciation for singular gifts and insights.”

Dr Liu embodies this ideal, advocating for his patients for access to the best research advances, including genomics and clinical trials of promising agents.  At ASCO, he kindly highlighted some of the important findings from Chicago and offered context on why they matter to the field.

He told us one combination was “potentially transformative” and could be “practice changing” in lung cancer with more data.

Intrigued? To find out what these important trials are and which ones to watch out for, subscribers can log-in to read the article.

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One thing has become very clear in the oncology space over the last year… checkpoint inhibitors are insufficient on their own for the vast majority of tumour types and patients that they have been explored in to date.  There are a number of reasons for this, but the main one is lack of T cells in the tumour, which enable an effective immune response to be mounted.

This begs the question – how can we address that issue and manipulate the tumour microenvironment in our favour, thereby making subsequent checkpoint blockade more effective?

There are a number of different ways to do this.

In the past, we’ve discussed several methods including innate immunotherapies such as Aduro’s STING or Biothera’s immunotherapeutic, Imprime PGG.  Other approaches include vaccines, which we have discussed in detail, t-cell receptors (TCR) or even monoclonal antibodies, such as AdaptImmune’s approach with their ImmTac technology.

There are other novel strategies currently being investigated by numerous companies too.

In this article – and also the second part of the latest miniseries – which will post tomorrow, we straddle our final reviews of interesting data from the European Cancer Conference (ECC) in Vienna with the upcoming one from the Society of Immunotherapy for Cancer (SITC) being held in National Harbor, Maryland.

Today’s post explores the concept of immunocytokines, engineered antibodies that are designed to boost the immune system, so that subsequent therapies will be more effective.

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On Friday last week, AstraZeneca confirmed that their combination trial for osimertinib, as it’s expected to be called or AZD9291, as it’s more commonly known (anti-EGFR mutant, T790M inhibitor) plus durvalumab (MEDI–4736, anti-PD-L1) in non-small cell lung cancer (NSCLC) is on clinical hold following an increase in ‘interstitial lung disease-like reports.’

As companies with checkpoint inhibitors and other immunotherapy agents expand beyond monotherapy into logical combinations, is the risk of increased ILD from combining an EGFR inhibitor with a checkpoint something other companies need to watch out for?

By the way, we strongly disagree with the reported conclusion of Goldman Sachs on this issue – and here’s why…

Today’s article explores this controversial issue in more depth.

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