Previewing the 2018 Rational Combinations 360 Conference

Over the last several years, immunotherapy has begun to change the cancer treatment landscape—for some patients.

By themselves, today’s most promising immunotherapies still only benefit a fraction of those with cancer, but by combining different immunotherapies together as well as with other treatments such as chemotherapy, there’s hope that its benefits can be brought to bear against all types of cancer.

On September 13 and 14, some of the most innovative minds in the field of immunotherapy will convene to discuss this important topic at the Wyndham Philadelphia Historic District for the 3^rd annual Rational Combinations 360° conference. As with the previous events in the series, the Cancer Research Institute (CRI) is proud to be a partner for the 2018 event, which is being hosted by The Conference Forum.

“There’s a very exciting future for combinations,” according to Patrick Hwu, MD, of the University of Texas MD Anderson Cancer Center, “but we have to have some way to rationally design these studies and also to decide upon the right agents.”

Determining the best way to do that is the goal of Rational Combinations 360, for which Hwu is a co-lead advisor along with GlaxoSmithKline’s Axel Hoos, MD, PhD, and Janssen’s Ian McCaffrey, PhD By bringing together researchers, physicians, industry executives, and investors, among others in the oncology space, the conference aims to foster innovative strategies to help maximize the potential of immunotherapy combinations.

Traditionally, Hoos noted, combination decisions have “often, but not always” been based on what’s worked before. “What are the existing treatments? How can you improve on that? The answer is that you add on to existing agents.”

Chemotherapy has been used in many combinations, as have checkpoint immunotherapies targeting the PD-1/PD-L1 pathway, which have been approved by the FDA as single agents in eleven types of advanced cancer.  As of last September, these immunotherapies were being evaluated in more than 1,000 combination trials, according to the landmark immuno-oncology landscape analysis published last year by the Cancer Research Institute.

Some of these combinations work—combinations involving PD-1/PD-L1 immunotherapies have been approved for patients with advanced melanoma, lung cancer, kidney cancer, and colorectal cancer—but many don’t.

Consequently, both Hwu and Hoos, who are both members of the CRI Scientific Advisory Council, recognize the need for better ways of designing combination strategies and pairing them with patients in the clinic.

“There is not going to be one combination that will work for everybody,” Hoos acknowledged. Instead, it’s about “finding the right combination for the right subpopulations [of patients].”

“The best way to do this,” according to Hwu, “is with strong science and with strong models.”

Both Hwu and Hoos agreed that biomarkers, which can provide insights about a patient’s cancer as well as their immune system, will be crucial in this regard. Some biomarkers—such as PD-L1 expression, and high microsatellite instability (MSI-hi)—have already shown clinical value and been incorporated into FDA approvals for PD-1/PD-L1 immunotherapies.

By themselves though, they can’t perfectly predict who will respond and who won’t. As a result, new biomarkers will be needed to complement existing biomarkers and thereby improve immunotherapy-related treatment decisions, especially when it comes to determining the agents that might combine most effectively for particular people.

Therefore, it’s likely that panels of biomarkers will have to be employed, “because no one biomarker seems to separate the responders and non-responders as cleanly as we need to make clinical decisions,” noted Hwu. “If we have a biomarker or combination biomarkers that tell us a patient is definitely going to respond, that’s helpful. It’s also helpful if we have some biomarkers that tell us a patient’s definitely not going to respond because then we won’t waste the patient’s time and money putting them on that drug.”

This capability, he continued, “could help us get patients the right drug first…and help society save some money by not putting patients on drugs that aren’t going to work for them.”

Throughout the two-day conference, various sessions will discuss combinations involving checkpoint immunotherapies, cellular immunotherapies like CAR T cells, bispecific T-cell engagers (BiTEs), and other novel immune-based treatments. The roles of technologies such as tumor explant models, single cell analysis, and TCR sequencing will be highlighted for their potential to shed light on the mechanisms behind immunotherapy’s effects as well as immunotherapy resistance. The impact of the gut microbiome in immunotherapy is another particularly exciting area that will be explored.

Beyond the purely scientific questions that will be addressed, Rational Combination 360’s sessions will also focus on considerations relating clinical trial design, the harmonization of biomarkers, the scalability of T cell immunotherapies, and, perhaps most importantly, collaborations and partnerships. The ability to even begin confronting these challenges speaks to the breadth of expertise that will be present at the conference.

“I think if we really want to make the maximum impact, [these experts from different domains] really have to be in the same room together,” Hwu emphasized, “because there are some issues that are very important for implementation and maximum impact that an academic investigator may not think about, such as scalability of a potential product.”

“In addition,” he continued, “maybe in the biotech community, in some circumstances they could really benefit from a strong model or scientific component that’s only available in academia. The more perspectives we can have, the better.”

When asked what they were looking forward to most about this year’s meeting, both Hwu and Hoos pointed to the potential of combination immunotherapies, and their hopes for how how the meeting can help advance the field.

“It’s going to be fun to see everyone’s ideas and have robust discussion amongst the group,” declared Hwu, “so we can more strategically plan tomorrow’s studies to enhance the potential effectiveness…of the next wave of combinations. What we want is to be able to make an impact in society and get successful combinations out there to the patients.”

In that same vein, Hoos was most excited about “seeing the evolution of the space—and, you know, it’s never fast enough for anybody…The field has grown. The investments are growing. There is data coming. It comes in small steps, but it’s coming. And you see the evolution and the progress that’s being made.”

In that regard, “the event will always deliver the cutting edge information in the space and tie it together in a way no other meeting does,” added Hoos. “There are things you can only do here that you cannot do at any other venue because you never get all the stakeholders in one place. It’s meant to be broad, to offer something for all stakeholders in the field, and enable you to network across the entire spectrum and find new collaborations, find new insights, and tie together data points that you may have not thought about as connected. That’s what 360 is meant to be.”

Be sure to check back here post-conference, as our blog will be updated with a recap of the highlights from the 2018 Rational Combinations 360 conference.

Banner image photo by Bryan Colosky on Unsplash.