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

Posts tagged ‘Atezolizumab Bladder Cancer’

Florence, Italy: Today at the EACR-AACR-SIC Conference on “The Challenges of Optimizing Immuno and Targeted Therapies,Tom Powles MRCP MD, Clinical Professor of Geniturinary Oncology at Barts Cancer Institute in London, gave a special lecture on the IMvigor211 trial (NCT02302807).

EACR AACR SIC Conf Banner

This was a phase 3 study of the PD-L1 checkpoint inhibitor atezolizumab compared with chemotherapy in participants with locally advanced or metastatic urothelial bladder cancer.

Prof Tom Powles (Barts)

Prof Tom Powles (Barts Cancer Institute)

Readers may recall we interviewed Prof Powles back in August 2015 about the potential for the PD-L1 checkpoint inhibitor atezolizumab in urothelial bladder cancer? (See post: Atezolizumab PD-L1 Checkpoint Inhibitor will Change Bladder Cancer Treatment.)

We also featured the atezo data presented by Dr Jonathan Rosenberg (MSKCC) at ESMO 2015 on Episode 7 of the Novel Targets Podcast, where we also heard Prof Powles tell us about the long durable responses he had obtained in clinical practice in some of his patients.

Subsequently on May 18, 2016 the US Food and Drug administration (FDA) granted accelerated approval to atezolizumab (Tecentriq) for urothelial bladder cancer (link to news release).

Fast forward a year to May 9, 2017 and the surprise announcement that the confirmatory phase 3 trial (IMvigor211) failed to meet its primary endpoint (link to Genentech press release).

So what happened? Why did the atezo phase 3 trial end up being negative when we saw durable responses in the randomised phase 2 trial and other PD-1 checkpoint inhibitors have shown an overall survival benefit in the same indication?

Many in the media only want to write about positive data, but in science we often learn as much from our failures as we do from our successes, perhaps even more sometimes.

IMvigor211 was expected to be a positive trial especially after the recent Merck success gaining an overall survival benefit for pembrolizumab, so the negative result is noteworthy and one that anyone in the field of cancer immunotherapy drug development will want to understand.

Professor Powles kindly spoke to BSB and shared his perspective.

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Vienna, Austria: it’s day 2 of the European Cancer Congress in Vienna (Twitter #ECC2015).European Cancer Congress Vienna

Along with 18,000+ attendees we’re looking forward to hearing about some more practice changing data.

Today in Vienna brings another busy and jam packed day at the European Cancer Conference (ECC).  We’ve already reached the point where the days blur and you have no idea which day of the week it actually is, you just follow the next fresh day in your personalised program or schedule.

So what’s in store today?

This morning brings updates on lung cancer, including the much anticipated atezolizumab results in POPLAR and BIRCH, as well as urothelial bladder cancer from the IMVigor trial. There is also a melanoma session that includes the oncolytic virus T-VEC, together with pembrolizunab and cobimetinib in separate study readouts. All this before lunch!

The afternoon promises to be equally interesting with an Immunotherapy in Cancer session that includes nivolumab, pembrolizumab plus we get our first look at a novel immunocytokine targeting CEA-IL2. A parallel session explores the science behind brain tumours with presentations on the tumour microenvironment, biomarkers and current trials.

In the meantime, the embargoes lift at 7am CEST on several studies including the atezolizumab data, which we highlight here.

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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 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.

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Chicago – the cancer immunotherapy poster session yesterday morning was “mobbed,” that is the only word to describe it. I have never seen such a crowded poster session at any medical meeting before. It speaks to the huge interest in this growing field.

ASCO 2015 Cancer Immunotherapy Poster Session

It’s also a reflection that insights into the future direction of the field will be found in posters about preclinical and early work, rather than in oral presentations that reflect strategic decisions made a long time earlier.

We know checkpoint inhibitors work in many cancers, and a few more have been added to the list at this meeting. While that’s interesting, the real question is how do we increase the response rate and also get them to work in non-immunogenic tumors?

Yesterday in the poster session at ASCO, there was a poster that caught our attention on one approach that may achieve this. We briefly wrote about it in the ASCO Day 2 blog.

Also of note yesterday was that the new generic name for the PD-L1 checkpoint inhibitor from Roche/Genentech. MPDL3280A is now atezolizumab. A few presenters stumbled over the pronunciation, it was so new…… and all the z’s add to the trickiness!

As to what Day 3 at ASCO holds, we’ll be updating this blog during the day as our schedule permits.

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