One thing has become very clear in the oncology space over the last year… checkpoint inhibitors are insufficient on their own for the vast majority of tumour types and patients that they have been explored in to date. There are a number of reasons for this, but the main one is lack of T cells in the tumour, which enable an effective immune response to be mounted.
This begs the question – how can we address that issue and manipulate the tumour microenvironment in our favour, thereby making subsequent checkpoint blockade more effective?
There are a number of different ways to do this.
In the past, we’ve discussed several methods including innate immunotherapies such as Aduro’s STING or Biothera’s immunotherapeutic, Imprime PGG. Other approaches include vaccines, which we have discussed in detail, t-cell receptors (TCR) or even monoclonal antibodies, such as AdaptImmune’s approach with their ImmTac technology.
There are other novel strategies currently being investigated by numerous companies too.
In this article – and also the second part of the latest miniseries – which will post tomorrow, we straddle our final reviews of interesting data from the European Cancer Conference (ECC) in Vienna with the upcoming one from the Society of Immunotherapy for Cancer (SITC) being held in National Harbor, Maryland.
Today’s post explores the concept of immunocytokines, engineered antibodies that are designed to boost the immune system, so that subsequent therapies will be more effective.
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For some time now there has been much debate about finding a predictive biomarker of response for EGFR monoclonal antibodies used in the treatment of advanced colorectal cancer. These include cetuximab (Erbitux) and panitumumab (Vectibix).
After all, we know that they tend to work in wild type disease (as shown in the US label below) and that KRAS and NRAS mutations on codon 12 and 13 on exon 2, as well as others on exon 3 and 4 tend to portend resistance to therapy, but beyond that not much is known.
At the European Cancer Conference in Vienna last month I was intrigued to see some new data emerge that may help researchers better understand and predict which people with metastatic colon cancer are more likely to respond in the future.
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Beyond the late breaking abstracts and plenary sessions at the European Cancer Conference being held in Vienna, Austria later this month, what other important topics can we expect to hear about?
We covered the former in the last article on Biotech Strategy Blog, today we turn our attention to the proffered (oral) sessions and what we can learn from those sessions and the expected data that is due to be presented.
There are a number of interesting topics and new data slated for presentation that are worthy of review and highlighting in a What To Watch out For (W2W4) format.
Here’s our take on the potential highlights at the meeting.
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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.
Readers 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.
This 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.