Biotech Strategy Blog

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

LONDON – atezolizumab (Roche/Genentech) is expected to change the standard of care (SOC) for the treatment of metastatic urothelial bladder cancer. That’s the key message I took from a recent interview with Professor Tom Powles (Barts Cancer Institute) on the role checkpoint inhibitors and cancer immunotherapy will play in the treatment of bladder cancer.

Professor Tom Powles BartsReaders will recall the compelling early phase 1 clinical trial data for atezolizumab (formerly MPDL3280A) that Prof Powles (pictured right) presented just over a year ago at the 2014 ASCO annual meeting: “Making a difference in advanced bladder cancer

Although other checkpoint inhibitors are in bladder cancer trials, and we have written about the pembrolizumab (Merck) data first presented at ESMO 2014 (“Breathing New Life into Bladder Cancer Treatment), it is expected that atezolizumab will win the race to market in the US and be the first checkpoint inhibitor to gain FDA approval for the second-line treatment of advanced bladder cancer.

Atezolizumab received breakthrough therapy designation (BTD) in May 2014 from the US Food and Drug Administration for PD-L1 positive metastatic urothelial bladder cancer after progression or intolerance of platinum based chemotherapy.

Earlier this summer Genentech announced in a press release that the IMvigor 210 phase 2 study was positive and met it’s primary endpoint, with a greater response rate associated with higher levels of PD-L1 expression.

European Cancer Congress 2015This data will be presented on Sunday Sept 27 as a late-breaker at the forthcoming 2015 European Cancer Congress in Vienna (Twitter #ECC2015), the European equivalent of the ASCO annual meeting organized in alternate years by ECCO and ESMO:

Atezolizumab in patients (pts) with locally-advanced or metastatic urothelial carcinoma (mUC): Results from a pivotal multicenter phase II study (IMvigor 210)

Although we won’t know the trial results until they are presented in Vienna by Dr Jonathan Rosenberg (MSKCC), based on the recent press release it’s widely expected that the positive data from this trial will lead to rapid regulatory approval in the United States.

Subscribers can login below or you can purchase access to read Prof Powles’ opinion on the role checkpoint inhibitors will play in the treatment of bladder cancer, how this may play out in Europe as compared to the United States, and what the future may hold beyond checkpoint monotherapy.

This interview does not discuss the data to be presented at the 2015 European Cancer Congress, the results of which we will have to wait until Vienna to hear.

It’s time for the August mailbag where we answer questions about cancer research and R&D from subscribers.

After the recent queries about immuno-oncology, it’s time to focus a little on targeted therapies again. Neither chemotherapies nor targeted therapies are going to go away – they are still the bedrock of many treatment approaches in the clinic today. Sadly though, much of the new data for the latter trials were easily swamped by the sheer tsunami of immunotherapy data in Philadelphia (AACR) and Chicago (ASCO).

One important area that we have been discussing on both blogs for some time is the value of well designed basket trials.  It’s time to revisit this concept in the light of new data relating to the BRAF V600 mutation outside of metastatic melanoma.

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The immuno-oncology space continues to get both interesting and also very crowded with over 20 chimeric antigen receptor (CAR) T cell therapies now in development. Originally, the excitement began with the University of Pennsylvania’s dramatic announcement regarding the first two advanced CLL patients they successfully treated, leading to a collaboration with Novartis and spurring a new ‘arms race’ development in this niche.

While most of the CAR T cell therapy data since has largely focused on acute lymphoblastic leukemia (ALL) and to a lesser extent, non-Hodgkins lymphoma (NHL), many have been wondering what was happening on the CLL front?  Has hope been abandoned there or will we see a renaissance occur?  It is of particular relevance with the Abbvie/Genentech announcement that venetoclax has positive data in CLL patients who have the Del17p mutation and filing is likely here in this subset soon.  Therapies such as ibrutinib and idelalisib are already approved in refractory CLL and may also have a future role to play here.

Do we need suicide switches for CAR T cell therapies such as Bellicum and Cellectis are developing or not?

Meanwhile, other hematologic malignancies are also being explored, including multiple myeloma. Why would a CD19 CAR work in a disease long considered to be CD19-negative in advanced, refractory disease?

Carl June UPenn

Dr Carl June, U Penn

What about progress with solid tumours? Many commentators and investors have been highly sceptical of the chances of success here following the advent of positive checkpoint data beyond metastatic melanoma and early CAR data in mesothelin cancers.

To answer these questions and also get a flavour for where things are headed with CAR T cell therapies, we recently interviewed one of the leading experts in this field, Dr Carl June (U Penn).

To learn more about Dr June’s perspective, subscribers can log in below or you can sign up in the box.

At the recent American Association of Immunology (AAI) and American Society of Gene & Cell Therapy (ASGCT) meetings in New Orleans, we had the good fortune to interview a number of leading cancer immunologists about their work. Some of these have already been published either here on Biotech Strategy Blog, or on the Novel Targets podcast.

In the meantime, the huge tsunami of data from the annual meeting of the American Society of Clinical Oncology (ASCO) hit and we have been a bit backlogged! Time to address that and focus on some more thoughtful reflections about where the cancer immunotherapy field is going.

Already, we are seeing another round of new collaborations and deals hit the newswires with AstraZeneca announcing two collaborations, one with Inovio on the INO–3112 HPV cancer vaccine and another with Heptares, where they acquired the exclusive global rights to develop, manufacture and commercialise the adenosine A2A receptor antagonist, HTL–1071. The first involves a cancer vaccine and the second immune escape mechanisms.  Not to be outdone, their rivals Clovis also announced a collaboration with Genentech to explore rociletinib (EGFR T790M) with atezoliumab (anti-PD-L1) in EGFR mutation-positive lung cancer.

Cancer vaccines have not, however, been a very successful or fertile area of R&D for Pharmaland to date, with only one such therapy approved by the FDA (sipuleucel-T or Provenge) and literally hundreds of other such compounds consigned to dog drug heaven. This illustrates the sheer enormity of the task we need to undertake in stimulating the body’s immune system to successfully attack the cancer in a sustained and robust way.

Dr Rosenberg, NCI

Dr Rosenberg, NCI

Despite this setback, there is still notable interest in exploring the innate immune system and finding effective ways to target and stimulate the T cells or T lymphocytes to attack the cancer.

One man who has accomplished an incredible body of work over the last two to three decades is Dr Steven Rosenberg from the NCI’s Surgery Branch (right).

No one who attended any of the cancer conferences where he spoke at over the last year is ever going to forget the dramatic before and after slides of remarkable transformation in his patient case history examples using Tumour Infiltrating Lymphocytes (TILs) as this example illustrates:


To learn more about Dr Rosenberg’s work and insights, you can sign in or subscribe in the box below to read our latest thought leader interview in the cancer research field.

William Coley first used live bacteria as an immune stimulant to treat cancer way back in 1893. Since then, however, progress with innate immunotherapy has been surprisingly very slow.

English Roses

Queen Mary Rose Garden, Regents Park, Summer 2015

Indeed, to date only one therapeutic cancer vaccine has actually been approved by the FDA (Sipuleucel-T, Provenge, Dendreon), one oncolytic virus was approved in China back in 2006 (H101, a direct derivative of the E1B55k-deleted Onyx-015 that had modest activity at best) and another could soon be approved by the FDA later this year (T-VEC, Amgen).

In today’s review, we take a look at the oncolytic viral space and explore the issues, challenges and companies involved. Is this all set to be a bed of roses, or is a thorny future predicted?

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Over the last year or two, we have covered a number of different pathways that are involved with the immune system including CD19 and 20, CTLA–4, PD–1 and PD-L1, IDO1, CD40, OX40, TIGIT, ICOS and others.

Today, it’s the turn of an oncoprotein called NY-ESO–1 that has been garnering quite a bit of attention of late and will also be highly relevant to some upcoming posts and thought leader interviews we have scheduled here on Biotech Strategy Blog. It’s always a good idea to cover the basics first, before exploring the more advanced concepts.

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We have followed the roller coaster development of the Bcl2 inhibitor, venetoclax (ABT–199/GDC–0199), for several years now.  There have been some lowlights along the way, but lately, things have been much rosier for AbbVie and Genentech as a more sensible dosing and patient management approach has been paying off.

Recently at ASCO and ASH, we have seen encouraging new data emerge in leukemia (AML and CLL), lymhomas (NHL), and even multiple myeloma.

New data has now emerged that looks quite interesting in another blood disorder. Today, we took a look at the data and also the potential implications for venetoclax’s development program.

To learn more about these insights, subscribers can login or you can sign up in the box below to learn more about the latest developments.

New developments in renal cell carcinoma

Continuing our focus on genitourinary (GU) cancers this week, today we turn our focus from prostate cancer to renal cell carcinoma (RCC).

There were two important announcments on Monday this week relating to renal carcinoma.

Firstly, Exelixis announced positive top line data from a phase 3 pivotal trial of cabozantinib versus everolimus in relapsed metastatic renal cell carcinoma (METEOR).  The study met the primary endpoint (i.e. significantly improved progression free survival) and the company revealed the following data:

  • Cabozantinib reduced the risk of disease progression or death by 42%; Hazard Ratio = 0.58, (p < 0.0001) compared to everolimus
  • Interim Analysis of OS demonstrated a trend in favour of cabozantinib; Hazard Ratio = 0.67, (p = 0.005) compared to everolimus
  • Exelixis to complete US and EU regulatory filings in early 2016

Secondly, a press release from BMS highlighted the phase 3 CHECKMATE–025 trial comparing nivolumab to everolimus, also in relapsed metastatic RCC, where the independent Data Monitoring Committee recommended early stoppage on the basis of the primary endpoint (OS) being met. The company likely be seeking discussions with Health Authorities with a view to filing the data with the FDA and EMA.

There are some interesting points that fall out of these releases. To learn more, subscribers can log-in below or you can purchase a subscription in the box below.

With the launch of Episode 4 of the Novel Targets podcast today, I wanted to provide some more detailed background and a roadmap for this part of the journey for subscribers. There’s tremendous wealth of data now building up in several areas related to cancer immunotherapy and both interviewees, Drs Oliver Sartor (Tulane) and James Gulley (NCI), touched on many of them.

Thanks to Tom Gajewski’s exciting work, we can broadly think about different tumour types as inflamed (immunogenic) versus non-inflamed (non-immunogenic), which is a helpful starting point. Not all tumours thought to be responsive to immunotherapy will actually respond though, so we still have much work to do on the 70–80% of patients with solid tumours that don’t respond to these therapies.

Anyone who is interested can listen to the latest Novel Targets podcast.

The latest episode explores non-immunogenic tumours, using prostate cancer as an example. In the last third of the show, we do indeed talk about a promising new target that may have relevance not just to prostate cancer, but other tumour types too.

Listen to Episode 4  (open access thanks to our sponsors, Genentech)

BSB Subscribers can learn more in-depth information and insights about this emerging field by signing in or you can sign-up in the box below.

Last month’s Biotech Strategy mailbag – where we answer questions from subscribers – turned out to be rather controversial with strong feelings running in several camps on Puma Biotech’s neratinib in breast cancer.

This time around we have a bunch of questions on completely different topics and compounds to cover:

  • BRAF plus MEK and/or immunotherapy in BRAFV600 metastatic melanoma
  • Immunogen’s IMGN853 – now known as mirvetuximab soravtansine – in platinum resistant ovarian cancer
  • AbbVie/Genentech’s ABT–199/GDC–0199 venetoclax

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