Biotech Strategy Blog

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

Posts from the ‘Lung Cancer’ category

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 or you can sign-up by clicking on the Blue Box below.

It’s Friday 13th, a day often feared by the superstitious, but for AstraZeneca it certainly portended good news with the FDA approval of AZD9291 or osimertinib (now Tagrisso) in EGFR T790M mutation-positive lung cancer – three months ahead of the PDUFA date. Jonathan Rockoff, a reporter at the WSJ, was the first to announce it in my Twitter stream:

Tagrisso 80mg

Tagrisso 80 mg. Picture credit: AstraZeneca

The FDA announcement for Tagrisso (generic name is osimertinib) can also be found here and the actual label here.

Note that it is now available under accelerated approval, based on tumor response rate and duration of response. This means that phase III confirmatory trials, including survival data will be needed for full approval.

As part of our ongoing series on the T790M niche, this is also a timely opportunity to catch up with the latest data that was presented earlier this month at the AACR-NCI-EORTC Cancer Therapeutics and Molecular Targets meeting in Boston.

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With the recent approvals of nivolumab (Opdivo) and pembrolizumab (Keytruda) in advanced lung cancer as well as new checkpoint inhibitor data presented on atezolizumab at the European Cancer Conference in Vienna, there are several new lung cancer immunotherapy controversies to consider such as…

  • How do we choose between docetaxel chemotherapy versus anti-PD1/PD-L1 immunotherapy?
  • Which checkpoint should we choose?
  • Is the PD-L1 biomarker useful and important?
  • Do the company assays differ?
Dr Jack West

Dr Jack West

Dr Jack West (Seattle) got the ball rolling on some of these issues earlier this month, generating quite a spirited and useful debate on Twitter, demonstrating that clinical decisions in this area are not as cut and dried as many might think.

In addition, we spoke to a number of lung cancer experts in Vienna for their perspectives on the data, the biomarkers, treatment paradigms and other critical issues.

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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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Over the last decade we have seen some real progress with some subsets of lung cancer, particularly in EGFR mutated and ALK translocated tumours.  Indeed, an incredible amount of translational work has emanated from just a few groups based in Boston, New York and Hong Kong.

Dr Jeff Engelman Source: MGH

Dr Jeff Engelman Source: MGH

At AACR earlier this year, Dr Jeffrey Engelman (MGH, Boston) gave a fantastic talk not just about heterogeneity, resistance mechanisms, but also on how lung cancer can transform. Included in his review was the role of biospies and how he sees those evolving.

I’ve been meaning to write up this important talk since April, but decided to wait until the key publications that were in press at the time were actually published – it was a longer wait than expected!

In general, it is our policy to write up published, rather than unpublished data, out of respect to researchers.  It also makes it more useful to readers when the translational and clinical data is publicly available for those interested in reading the in-depth research articles.  We also gathered commentary from other though leaders in the lung cancer space for some additional insights.

To learn more about the latest developments in the underlying complexity and clinical implications for EGFR+, T790M-positive and ALK-positive lung cancers, subscribers can log in below or you can sign up to read our comprehensive review of this topic.

AAI LogoNew Orleans – At the 2015 annual meeting of the American Association of Immunologists (AAI) leading experts came together to share their insights on the Promise of Cancer Immunotherapy.”

The audience at #AAI2015, in an artic chilled hall, heard from an outstanding panel of speakers, many of whom flew in specially:

  • Immunologic Checkpoint Blockade: Combinations and Mechanisms, Jedd Wolchok (MSKCC)
  • Immune Checkpoint Therapy: Clinical Success and Next Steps, Padmanee Sharma (MD Anderson)
  • Improving Cancer Treatment Through Immunotherapy Combinations: Combination MAb Therapy: Dual tumor & Immune Targeting, Holbrook Kohrt (Stanford Cancer Institute)
  • Curative Potential of T-Cell Transfer Immunotherapy for Cancer, Steven Rosenberg (Surgery Branch, NCI)
  • PD-1 pathway blockade in cancer therapy: new frontiers, Suzanne Topalian (Johns Hopkins)
Dr Steven Rosenberg (NCI)

Dr Steven Rosenberg (NCI)

Cancer Immunotherapy is such a fast-evolving field that at Immunology 2015, we heard data that wasn’t at the annual meeting of the American Association for Cancer Research (AACR), just a few weeks ago.

Several presenters also put in context data that will published at the forthcoming ASCO annual meeting.

If you’d like to hear more about some of the checkpoint inhibitor data at AACR15, do listen to the first episode of the Novel Targets podcast (if you haven’t already done so).

It’s available as a free download on SoundCloud and on iTunes.

This post offers a top-line summary of some of the key messages we heard in the #AAI2015 symposium.

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With the sheer breadth and depth of immuno-oncology data being presented at even the American Association for Cancer Research (AACR), several readers were prompted to write in and ask:

“Is this the end of the road for TKI therapies? Should we even bother to continue working on these agents?”

Good question.

There was actually quite a bit of interesting data on regular novel targeted therapy to discuss, although I do concede that much of the mass media news focusing on the immuno-oncology tsunami in Philadelphia effectively drowned out targeted therapies and the results coming out in that space.

Reading Market Philly Chocolate TowerTo maintain the balance between novel targeted agents and immunotherapy, here’s a review of some of the interesting new developments that I came across at AACR, from both the poster halls, as well as some of the thought leaders in this space.

When you stack up the emerging evidence in several tumour subsets, there are quite a few tasty morsels that are worthy of further discussion!

I’d like to take this opportunity to extend a warm welcome to all the new subscribers who took advantage of the AACR Special Offer to continue their education and learning about the exciting new developments in cancer research.  Thank you for joining our conference coverage service, we really appreciate it.

To learn more about the hot topics in targeted therapies for cancer research, you can log in or sign up in the box below.  Read on…

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Philadelphia – the 2015 annual meeting of the American Association for Cancer Research (AACR) is in full swing, with over 18,000 attendees, it’s probably the world’s largest meeting dedicated to cancer research. The theme is “Bringing Cancer Discoveries to Patients.”

AACR 2015 Annual Meeting Philadelphia

I challenge anyone not to attend, and come away inspired with new ideas on how the field of cancer research will evolve in coming years.

At this year’s annual meeting, not surprisingly, cancer immunotherapy is one of the hot topics. Yesterday there was the simultaneous publication of two papers in the New England Journal of Medicine (NEJM) to coincide with data presented at the meeting.

Pembrolizumab (Keytruda)  for the Treatment of Non–Small-Cell Lung Cancer

The conclusion of the paper by Edward B. Garon, MD (UCLA) et al was that:

Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non–small-cell lung cancer. PD-L1 expression in at least 50% of tumor cells correlated with improved efficacy of pembrolizumab.

The other paper published in the NEJM was for:

Pembrolizumab (Keytruda) versus Ipilimumab (Opdivo) in advanced Melanoma.

The conclusion of the paper by Caroline Robert, MD PhD, presented at AACR by Antoni Ribas, M.D., Ph.D.(UCLA) was:

The anti–PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma.

AACR 2015 Press Briefing with Dr Topalian, Dr Ribas, Dr Garon

Dr Ribas (left) and Dr Garon (right) are pictured at an AACR media briefing chaired by Dr Suzanne Topalian (Johns Hopkins).

This year’s AACR annual meeting is to paraphrase Bertrand Tombal, “a Grand Cru year”. Not only in cancer immunotherapy, but in metabolism, epigenetics and advances in drug discovery.

We’re excited about the prospect of another three days at the meeting, but in the meantime in this post there’s some top-line thoughts for subscribers on some of the data that caught our attention over the weekend.

In recognition of AACR, there’s $50 off a quarterly subscription if you wish to purchase access (offer valid only during the week of the meeting – ends this Friday!)  If you’ve been sitting on the fence for a while wanting to try out BSB, now is a good opportunity to dip your toes in the water.

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European Lung Cancer Conference 2015Geneva – at the 2015 European Lung Cancer Conference today, Pasi A. Jänne, MD, PhD presented updated progression free survival and duration of response data for the phase 1 AURA trial of AZD9291 (AstraZeneca) in patients with EFGR-TKI-resistant advanced non-small cell cancer (Abstract LBA3).

Dr Jänne (pictured below at ASCO 2014) is Director, Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute and a Professor of Medicine at Harvard Medical School.

Dr Pasi Jänne ASCO 2014

It’s hard to believe that it is only about two years since the first patient was enrolled in the phase 1 AURA trial of AZD9291, a third generation EGFR inhibitor. If the FDA regulatory submission takes place, as expected, in the second quarter of this year, then the drug could be approved for sale in the United States before the year end.

It has been fascinating to watch the race to market between rociletinib (Clovis Oncology) and AZD9291. It’s likely both could be approved in the United States before the year end.

That would be great news for lung cancer patients, given the absence of any approved therapy for patients who develop a T790M mutation and become resistant to EGFR inhibitors, such as Tarceva and Iressa.

Readers will know that we have been following the phase 1 AURA trial of AZD9291 since ECCO 2013 in Amsterdam, when the first clinical data was presented.

AstraZeneca are to be congratulated on what is a case study of rational scientific drug development; their path to market strategy highlights the benefit of well-designed early clinical trials. AZD9291 may end up receiving regulatory approval less than three years from the start of the first in man trial – that’s tremendous!

I had the privilege to interview Dr Jänne at ASCO last year, and again earlier this week, before he left Boston for Geneva and chatted with him about his AZD9291 presentation at European Lung.

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