Biotech Strategy Blog

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

Posts tagged ‘Seattle Genetics’

The dog that didn’t bark

What do cancer drug development and Sherlock Holmes have in common?

The simple answer is that sometimes you can gain insights by looking at what did not happen.

Will belantamab mafadotin stand out in the crowded BCMA space?

In 1892 Sir Arthur Conan Doyle wrote a short story about the disappearance of a famous racehorse the night before a race. What was curious about the incident was that there was no barking from the watchdog when you might otherwise have expected it, suggesting the dog knew the thief…

Can we follow the same inductive reasoning when it comes to cancer drug development? Are there things we would expect to see, but don’t? If so, what inferences can we draw from them?

In this post we’re taking a closer look at the latest data for GSK2857916 (now belantamab mafadotin), which in many ways was “the dog that didn’t bark” at ASH19.

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On APHINITY, SOLO2 and Immunomedics

HI Koko Crater Flowers

Over the last week or so, we’ve received a lot of questions on the following topics relating to women’s cancers in breast and ovarian carcinomas:

  • APHINITY impact – pertuzumab and neratinib
  • PARPs in ovarian cancer – niraparib, rucaparib and olaparib
  • Seattle Genetics and Immunomedics

So this is probably a good time for a February BSB Reader Q&A post on the hot topics of the moment in cancer research.

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Seattle Genetics vadastuximab talirine and liver toxicities in AML

Yesterday sudden and unexpected news from Seattle Genetics caused quite a stir…

“Seattle Genetics Announces Clinical Hold on Several Phase 1 Trials of Vadastuximab Talirine (SGN-CD33A).”

Part of the Seattle Genetics exhibit booth at #ASH16, taken with permission

In short, over 300 patients have been treated with the ADC and six experienced hepatotoxicity, including several cases of veno-occlusive disease, with four fatalities.

We’ve written about AML several times recently and also received a number of reader questions on this latest development, so it’s time to explore the issue in more depth and look at the implications. We also include some expert commentary from a leukemia specialist for their take on the issue.

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ASH16 Preview on Acute Myeloid Leukemia AML

Post 2016 US Election, we move on and get back to business with an in-depth review of some new science and clinical data.

ash-2015Yes, it’s time for another Bushidō – “Way of the Warrior” – guide to the key ASH abstracts!

Here we focus on acute myeloid leukemia (AML), a difficult and challenging disease to treat with a high unmet medical need for new effective therapies.

In this Preview we look at key companies in the AML space, as well as a look at what’s happening in classic targets and also some new ones that are receiving notable attention, both preclinically and also in the clinic.

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The impact of niraparib on the ovarian cancer landscape

Tesaro’s niraparib is a highly selective poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor that can induce synthetic lethality in tumor cells with homologous recombination DNA repair deficiencies (HRD), including germline BRCA-mutated tumours.  It received a lot of attention yesterday following the company’s announcement that the phase 3 trial successfully met its primary endpoint.  The trial was expected to readout this month, so it was bang on schedule.

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Braving the scrum in the ASCO 2016 poster hall

The results generated a lot of discussion and also a bunch (half a dozen!) of questions from readers, since there was a lot noise around the top-line data in the press release, but very little real analysis or context.

I was planning on rolling out the draft posts we have been working on Gems from the Poster Halls, which included one focused on ovarian cancer.  It therefore makes sense to combine the poster analysis with a reader Q&A on ovarian cancer, including a detailed look at Tesaro’s niraparib as there are some important subtleties that many have missed.

Inevitably this ended up as a rather meaty analysis rather than the quick review I originally intended!

To learn more about the latest developments in PARP inhibitors and the ovarian cancer landscape, you can sign-in…

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ASCO 2016 Preview 1 – Novel Combination Approaches

For years we’ve followed the trials and tribulations of targeted therapies seeing many approved and quite a few disappear forlornly (and officially) off to dog drug heaven. Many more sit in no-man’s land as companies eagerly wait in a holding pattern for other trial readouts in different tumour types. Sadly, sometimes these studies don’t generate enough compelling data either. With so much competition about, there are no shortcuts or low-hanging fruit in biotech or cancer drug development any more.

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En route to Chicago and ASCO!

Then along came antibody drug conjugates (ADCs), with some encouraging results in a range of cancers in both solid tumours and hematologic malignancies that lead to the approval of several new therapies.

After that, the next big advance was immunotherapies, specifically checkpoint blockade, with encouraging single agent activity in melanoma, lung, and even urothelial bladder cancer. We’ve also seen the promise fo combining two different checkpoints such as nivolumab and ipilimumab together in metastatic melanoma, albeit with an increase in toxicities.

This is all very well and good, although the challenge remains that the majority of patients either respond to therapy and relapse, or do not respond at all, depending on the circumstances, the tumour type and the regimen. We still have a long way to go in moving the needle and creating a new paradigm shift on a broad scale.

So what happens when we start to combine modalities – such as targeted therapies with immunotherapies?

Uh-oh, I hear the distant cries of disagreement erupt…

  • Remember vemurafenib plus ipilimumab in metastatic melanoma was scuppered by severe hepatitis?
  • What about osimertinib plus durvalumab in NSCLC and the increased incidence of ILD?

Both of these statements are true, and yet… we should not assume that all mixed therapy combination approaches are doomed on the basis of a mere n of 2. What happens if some are synergistic or additive? What happens of there are hidden gems that teach us new ways of doing things rather than doing the same old thing just because it’s always been done that way?

With this in mind, I’d like to open the door on our first ASCO 2016 Preview series with a look at novel combination approaches in development that caught my eye.

What are the early hints and signals that we can learn from the data? Which companies are evaluating imaginative new ideas that may turn the tables on traditional thinking?  The ideas discussed here may well surprise a few people.

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AACR 2016 CD40 Cancer Immunotherapy

Dawlish TrainspottingIt’s Day 7 of our 12 day Countdown to AACR 2016 in New Orleans.  After exploring GITR and OX40, we’re now looking at another stimulatory target for cancer immunotherapy: CD40.

We’ve been writing about CD40 as a cancer immunotherapy target for some time. See posts: “CD40 as a Cancer Immunotherapy Target” and “Targeting CD40 in Cancer Immunotherapy.”

Anti-CD40 antibodies are agonists that act on stimulatory signalling receptors on T cells and antigen presenting cells (APCs). Targeting CD40 effectively acts to “put the foot on the gas” and may help generate a better immune response. This could be important in cancers that have fewer natural T cells present.

CD40 is an attractive target because it’s expressed in more than 50% of carcinomas and melanomas and almost all hematological B cell malignancies.  Of particular interest is the potential to combine a CD40 agonist with a PD-1/PD-L1 checkpoint inhibitor.

Multiple companies have CD40 agonists in clinical development including Roche, Apexigen, Alligator Biosciences and Seattle Genetics.  There are others coming too.

In this preview of AACR 2016, we’re looking at the CD40 landscape. New products and companies have entered the scene, so we’re highlighting them and some of the CD40 presentations to look out for at AACR 2016 (and why they matter).

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ASH15 Preview Checkpoints in classical Hodgkin Lymphoma

ASH 2014 cHL PembroOne of the hotly debated topics at the 2014 American Society of Hematology (ASH) annual meeting was the arrival of checkpoint data in classical Hodgkin’s lymphoma (cHL), with initial data presented on 20-30 patients with relapsed or refractory cHL who received either nivolumab (BMS) or pembrolizumab (Merck) in open label, single agent trials.

Updated phase I data is expected to be presented at the 2015 ASH annual meeting in Orlando (Dec 5-8) (Twitter #ASH15)

At the recent ESMO symposium on Immuno-Oncology in Lausanne (Twitter #Immuno15) – great hashtag, there was an excellent overview of checkpoint blockade in lymphomas. What did this tell us about progress in this disease and where are things going?

ESMO-Symposium-on-Immuno-Oncology-2015-banner

The ESMO IO meeting set the scene for what we can expect at ASH this year?

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CD40 as a Cancer Immunotherapy Target

There are now several CD40 agonist antibodies in early clinical development from several different companies, including:

  • Roche – RO7009789
  • Apexigen – APX005M
  • Seattle Genetics – SEA-CD40
  • Alligator Bioscience – ADC–1013

This post is the last in our cancer immunotherapy coverage from the European Cancer Congress in Vienna. It features excerpts from an interview with Dr Christian Rommel, head of oncology discovery at Roche in Basle, Switzerland in which he talks about the development of their CD40 monoclonal antibody. Readers may recall we wrote about this from SITC 2014 last year: “Targeting CD40 in Cancer Immunotherapy.”

This post is also a new primer on CD40 as we start our coverage of the Society for Immunotherapy of Cancer (SITC) 2015 annual meeting. We’re informed by SITC it’s a sell out conference with 600 more people than last year’s record breaking number. Cancer Immunotherapy is indeed the hottest topic in cancer drug development.

If you have plans to be at National Harbor this week, we hope to see you there!

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ASCO 2014 Diffuse Large B Cell Lymphoma DLBCL Progress

One of the overlooked highlights from ASCO this year was new data in diffuse large B cell lymphoma (DLBCL), which is an aggressive form of Non-Hodgkins Lymphoma (NHL). DLBCL is the most common form of NHL accounting for nearly one third of newly diagnosed NHL cases each year in the USA. Most of these people are adults rather than children.

The first sign of DLBCL is often a painless rapid swelling in the neck, armpit, or groin, which is caused by enlarged lymph nodes. Other symptoms can include night sweats, unexplained fevers, and weight loss.

Aggressive lymphomas such as DLBCL behave very differently from indolent NHL (iNHL) since they are faster growing and generally have a much poorer prognosis. As a result, they are treated much more aggressively with rituximab plus chemotherapy regimens such as CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Sometimes etoposide (E) is added in younger patients with a high disease burden, in which case the regimen is known as R-EPOCH.

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