In Anticipation of ASCO: What’s Next for Cancer Immunotherapy…? Combinations of Course!
By Alex Franzusoff, PhD, SVP Research & Development, Bavarian Nordic
This advertorial is brought to you by Bavarian Nordic.
Cancer immunotherapy, specifically a group of exciting new checkpoint inhibitors, captured the spotlight at last year’s annual ASCO meeting, and marked a turning point in the field of immune-based therapeutics for the treatment of cancer. Since then, excitement for immunotherapy has reached an all-time high, with promising new approaches and programs moving into clinical development, and many of us expect this excitement to continue at this year’s meeting. Thus, I wanted to offer an overview of one of the most exciting areas of clinical research that the Bavarian Nordic team is both pursuing and following: combination therapy.
At the conference, one of the most anticipated announcements will come from Merck, who is expected to announce data from multiple registration studies for their investigational anti-PD-1 antibody, MK-3475, also known as Pembrolizumab. These data, submitted as part of a rolling biologics licensing application (BLA), could potentially support a FDA approval for licensure in metastatic melanoma by year end. Merck has driven an extremely robust clinical development program of concurrent studies as monotherapy and in combination, across 30 indications, to advance MK-3475, and is truly paving the way in how we will evaluate these kinds of programs moving forward. Three other major Pharma players in the PD-1/PDL-1 immune checkpoint space, Bristol-Myers, Roche and AstraZeneca are following closely behind Merck with their own high profile cancer immunotherapy programs.
While Merck’s data will likely command considerable attention at the meeting, we are also expecting some very exciting work to be presented in the area of combination therapies, particularly trials exploring multiple cancer immunotherapy agents. This year’s meeting will undoubtedly give us our first glimpse into how some of these potential combinations may work. Whether that means combining multiple checkpoint inhibitors, or in Bavarian Nordic’s case, pairing a checkpoint inhibitor (CTLA-4 or possibly PD-1) with an active immunotherapy from our poxvirus-based platform candidates, we believe that this will ultimately be an important step in the development of immune-targeted therapies against cancer.
But first, let us take a step back and consider why this is potentially so exciting. With the advent of highly effective immune checkpoint inhibitor biologics, we’ve seen a fundamental change in how oncologists and drug developers view immune-targeted therapies. Prior to this, treatment with immunotherapy was seen as a progressive, long-term approach to slow cancer growth. However, this has now changed with the early successes of immune checkpoint drugs, which have demonstrated an accelerated, cytoreductive effect without the residual side-effects such as those seen with chemotherapy. This has led to a drastic change in perception of what immunotherapy can achieve.
In principle, immune checkpoint inhibitors should work for everyone. This “releasing of the brakes” on the immune system should allow the body’s own defense system to attack the cancer. We now know this is not always the case. Our belief is that patients with an underlying or endogenous anticancer immune response will benefit simply from this “unlocking” or “unjamming” of their immune system. However, for those patients that do not have that endogenous background immune response to their cancer, they may still require an immune “activation” against the cancer cells to kick start the immune system. This is where the potential to combine immune checkpoint inhibitors with active immunotherapies, which are designed to provoke a robust tumor-specific immune T cell response, offers such potential. Research to date suggests that by combining these immune-oncology therapies we can create an “on-the- gas/off-the-brake” dynamic. Physicians could administer a therapeutic active immunotherapy to “step on the gas” and trigger a targeted immune response against the cancer along with an immune checkpoint inhibitor to remove the brakes on the immune system so that the newly activated immune response is unleashed to its full cytoreductive anticancer potential. Not only could this lead to an amplified anticancer response by the patient, the resulting anti-tumor response could remain well after the treatment regimen is completed.
While these are still hypotheses that we as a company and an industry will be looking to confirm, I am confident that this year’s meeting will demonstrate that we are one step closer to unlocking the full potential of some of these exciting new combination immunotherapies.
For those interested in learning more on the topic at the meeting, there are a number of Educational Sessions worth checking out, including:
Immunotherapy: Transforming Frustration to Cure in the Next 50 Years
Sunday | 4:45 PM – 6:00 PM | Education Session
Innovative Strategies for Picking Combination Therapy Regimens
Tuesday | 8:00 AM – 9:15 AM | Education Session
Bavarian Nordic will also be presenting data on our lead immunotherapy program, PROSTVAC®, including two posters examining the potential benefits of PROSTVAC® in combination with checkpoint inhibitors. The details are as follows:
“Anti-tumor efficacy of poxvirus-based active immunotherapy alone and in combination with sub-therapeutic dosing with immune checkpoint inhibitors”
General Poster Session, Developmental Therapeutics: Immunotherapy, Sunday, June 1, 2014 from 8:00 AM to 11:45 AM. The abstract can be seen at the ASCO Annual Meeting website: here
“Magnitude and quality of tumor-infiltrating T cell response upon poxvirus-based active immunotherapy alone and in combination with CTLA-4 immune checkpoint inhibition”
Poster Highlights Session, Developmental Therapeutics: Immunotherapy, Monday, June 2, 2014 from 1:15 PM to 4:15 PM. The abstract can be seen at the ASCO Annual Meeting website: here
See you in Chicago!
About Bavarian Nordic
Bavarian Nordic is an international biotechnology company developing and manufacturing novel cancer immunotherapies and vaccines for infectious diseases. Lead product candidates are PROSTVAC®, an immunotherapy product candidate for advanced prostate cancer that is the subject of an ongoing pivotal Phase 3 clinical trial, and IMVAMUNE®, a non-replicating smallpox vaccine candidate in Phase 3 development, which is being developed and supplied for emergency use to the U.S. Strategic National Stockpile under a contract with the U.S. Government. The vaccine is approved in Canada under the trade name IMVAMUNE and in the European Union under the trade name IMVANEX®.