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

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A Busy Monday at AACR 2017

Washington DC – there was so much noteworthy science on display at the annual meeting of the American Association for Cancer Research (AACR) on Monday that hard choices had to be made on what data to see in person.

Despite spending several hours in the poster sections of the exhibit hall, there was only the chance to see a small sample of the posters on display, each representing the culmination of months or years of work.

Poster Hall at AACR 2017 annual meeting

We will be writing our popular “Gems from the AACR Poster Hall” posts in due course.

It’s hard to convey how busy a meeting this is, unless you’ve been. Thousands of posters are shared, multiple sessions run in parallel, and that’s not to mention finding the time for 1:1 expert interviews. There is never much down time.

The challenge for many is that the more you know, the more you realise you don’t know. From a media perspective there is no shortage of questions to ask or important topics to cover.

Yet what really makes this meeting exciting is that it provides a glimpse of the future and the hope that offers. The cancer drugs of the future are being talked about at this meeting.

Today’s BSB post offers commentary around on what caught our attention at an extremely busy Monday at #AACR17 in Washington DC.

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Sunday at AACR 2017 annual meeting

Dr Tom Gajewski (Chicago) and Dr Roberta Zappasodi (MSKCC) in plenary biomarker session

Today, the 2017 annual meeting of the American Association for Cancer Research (AACR) kicked into gear with multiple sessions from early morning until late into the evening (Twitter #AACR17)

Above all else the meeting showcases the value of scientific research, and how improving our knowledge of cancer biology is the foundation upon which new drugs and therapies are developed.

If you know or want to know why cancer can be cured in mice but not in humans, then the AACR annual meeting is the place for you.

In today’s post we’re again providing some end of the day topline commentary on the sessions we attended and the data we heard. We also did several expert interviews that we’ll be writing up in forthcoming weeks.

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Reflections on Saturday at AACR17

Waiting in line for the White House Tour

The 2017 annual meeting of the American Association for Cancer Research in Washington DC (Twitter #AACR17) officially starts tomorrow, but today was a day full of educational sessions and workshops.

After a day of rain yesterday, it was good to have a dry day for the start of the world’s leading cancer science meeting.

In this post we offer some top-line commentary on those educational sessions we attended; the choice reflects personal interests or current fetishes.

By definition, there is far more excellent research at AACR than we can possibly cover on the blog; so we encourage you to check out the AACR webcasts if you have a specific interest or want to check out a particular session.

We’d also like to congratulate AACR for moving with the times and allowing personal photography and the sharing of content on social media, except where a slide or presentation says “Do Not Post.”

The few slides that I saw today that had “Do Not Post” showed unpublished data. Our longstanding unwritten policy has been not to tweet or share on social media data that clearly states it is unpublished, so this was not an unreasonable request and one we heartily concur with in principle.

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FDA Approval of Niraparib is a Failure for Precision Medicine

Following the recent approval of Clovis’s rucaparib (Rubraca) by FDA under priority review as monotherapy for the treatment of women with certain types of advanced ovarian cancer, then impressive SOLO-2 maintenance data after initial chemotherapy at SGO earlier this month, PARP inhibitors continue to be in the news.

There’s always more though!

This afternoon saw the approval of Tesaro’s PARP inhibitor niraparib (Zejula) by the US Food and Drug Administration (FDA) for maintenance treatment of women with ovarian cancer who are in a complete or partial response to platinum-based chemotherapy (Link to label).

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Novel Way to Improve Checkpoint Inhibitor Efficacy

We’re continuing our coverage of highlights from the inaugural ASCO-SITC Clinical Immuno-Oncology Symposium with a look at a novel way to potentially improve the efficacy of checkpoint inhibitors.

It’s not something we’ve previously written about, nor is it included in the recent Chen & Mellman Nature paper that discusses “factors that influence the cancer-immune set point.”

So there’s a good chance it may not be on your radar either.

Given the commercial stakes at play in improving checkpoint efficacy, combination strategies that could have an impact are worth thinking about when it comes to designing clinical trials.

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Novel Targets in Multiple Myeloma

Much of the focus in multiple myeloma over the last decade has focused on two key drug classes – proteasome inhibitors and IMiDs – with some recent approvals for monoclonal antibodies targeting key proteins on the surface of malignant myeloma cells such as CD38.

#ASH16 in San Diego

Combinations of these core therapies have lead to a noticeable improvement in outcomes for people living with the disease – from 3-4 years over a decade ago to now approaching 10 years post diagnosis.

If we want to continuously beat the status quo and improve on the chronicity, however, it is likely that several things will need to happen:

  • Better understand mechanisms of resistance that induce relapse
  • Develop predictive biomarkers of response
  • Identify novel therapeutic targets

Here. we focus on the latest preclinical findings that were recently presented at the American Society of Hematology (ASH) in San Diego and explore where the future might be headed in this disease.

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Targeting the tumour environment in Lymphomas

As we move from monotherapies to combinations in the immuno-oncology space, we start to see some intriguing ideas being explored from additional checkpoints to vaccines to neoantigens to immune agonists to oncolytic viruses. There are numerous ways to evaluate how to boost or jumpstart more immune cells upfront in the hope of seeing better efficacy.

One way to do this is to better understand the tumour microenvironment.

Wall of people at ASH16 in San Diego

If we know what’s wrong under the hood, we might be better able to make the immune system get going… more gas, faulty starter motor, dead battery, loose wire, broken fan belt? All these things and more might be a problem so you can see that diagnosing the issue up from from basic and translational work might be instructive for clinical trials.

If you don’t know what problem you’re trying to fix or repair then you might as well be throwing mud at the wall. Just as we don’t expect a car mechanic to suggest changing the battery or starter-motor without first diagnosing the issue, so understanding the tumour microenvironment in each different cancer or disease might also be a helpful strategy.

At the recent American Society of Hematology annual meeting (#ASH16), there was a fascinating sceintifc workshop that focused on this very concept – what’s going on under the hood and how do we go about fixing it?

Here we explore these ideas via an interview with a thought leader and specialist in the field. What he had to say was very interesting and candid indeed.

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Is Tucatinib better than Neratinib in HER2-positive Breast Cancer?

At the recent 2016 San Antonio Breast Cancer Symposium (SABCS16), Cascadian Therapeutics (NASDAQ: CASC) presented a poster (Abstract #P4–21–01) on:

“Efficacy Results of a Phase 1b Study of Tucatinib (ONT–380), an Oral HER2-Specific Inhibitor, in Combination With Capecitabine and Trastuzumab in HER2+ Metastatic Breast Cancer, Including Patients with Brain Metastases.”

Tucatinib is an oral tyrosine kinase inhibitor that is highly selective for HER2.

Cascadian’s tucatinib poster at #SABCS16

We’ve seen several new treatments approved for HER2 positive breast cancers in recent years including four targeted treatments: trastuzumab, pertuzumab, lapatinib and T-DM1.

Other companies such as Puma Biotech (NASDAQ: PBYI) also have oral TKIs in development. Puma’s drug, neratinib has, however been shown to have a high incidence of grade 3+ diarrhea, raising questions about its tolerance.

At SABCS16 (Abstract P02–11–03), the company presented the interim analysis of an open-label, multicenter phase 2 trial, which explored their compound:

“Incidence and severity of diarrhea with neratinib + intensive loperamide prophylaxis in patients (pts) with HER2+ early-stage breast cancer (EBC).”

There has been a lot of interest and controversy in this space, so it’s time to take a look at the latest events in HER2+ breast cancer and consider the ramifications since there are a number of new developments that are well worth following, including neratinib (Puma Biotech) and pertuzumab (Genentech).

This is our final expert interview from SABCS – if you missed it you can catch up with the rest of the conference coverage and thought leader sentiments here.

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Targeting Breast Cancer Stem Cells

Dr Max Wicha is the 2016 recipient of the AACR Distinguished Lectureship in Breast Cancer Research. At the 2016 San Antonio Breast Cancer Symposium (SABCS16) he gave his award lecture, “Targeting Breast Cancer Stem Cells: Challenges and Opportunities.”

SABC16 Dr Max Wicha Award Lecture

As the AACR press release notes, “This lectureship recognizes an outstanding scientist whose work has inspired or has the potential to inspire new perspectives on the etiology, diagnosis, treatment or prevention of breast cancer.”

Dr Wicha is a pioneer in the field of cancer stem cells, and is Director Emeritus of the University of Michigan Comprenhensive Cancer Center and a co-founder of OncoMed Pharmaceuticals (NASDAQ: OMED).

Targeting cancer stem cells is an area I expect we will hear a lot more about, particularly in breast cancer. Dr Wicha kindly spoke to BSB after his award lecture, which was one of my highlights of SABCS16.

In case you missed it, do check out the post from the 2016 EORTC-NCI-AACR Molecular Targets Symposium in Munich that featured Dr Mina Bisell (Berkeley), who was a previous recipient of the AACR Distinguished Lectureship in Breast Cancer Research award in 2012 (Link.)

This is the fifth in our series of expert interviews from the 2016 San Antonio Breast Cancer Symposium.

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Challenges and Opportunities in Inflammatory Breast Cancer

At the 2016 San Antonio Breast Cancer Symposium (SABCS16), I had the great pleasure to talk with a leading inflammatory breast cancer expert and translational researcher, Naoto T. Ueno MD PhD.

Dr Naoto Ueno at SABCS16

Dr Ueno is Executive Director of the Morgan Welch Inflammatory Breast Cancer Research Program and Clinic at the University of Texas MD Anderson Cancer Center.

He’s active on Twitter where, as @teamoncology, he shares information on the latest developments in breast cancer, often writing in Japanese for his followers.

A cancer survivor himself, he also brings an empathy to patient care through his own treatment experience.

Anyone who follows him on Twitter, will also know he is a “foodie.”  Prior to our chat, I joked he should write the definitive guide to San Antonio restaurants for attendees… he definitely ate better than I did at the meeting!

MD Anderson also has an IBC conference coming up next month for those interested in the area:

What caught my attention at SABCS16 were posters from MD Anderson researchers that offered insight into the challenges and opportunities in targeting this rare form of breast cancer, something we don’t hear a lot about.

Subscribers can login to read the interview Dr Ueno kindly gave BSB. This is the fourth in our series of expert interviews from San Antonio.

If you have a keen interest in IBC, do follow @teamoncology – if you don’t already!

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