Billed as “the premier meeting across all stakeholders in immuno-oncology,” the fourth annual Immuno-Oncology 360° (IO360) conference—held from February 7-9 at New York City’s Roosevelt Hotel—didn’t disappoint.
Like cancer, the immune system is complex, and while it’s potentially our most effective weapon against tumors, scientists are still learning how best to take advantage of its power through immunotherapy.
Fortunately, IO360’s two lead advisors—GlaxoSmithKline’s Axel Hoos, M.D., Ph.D., and the National Cancer Institute’s James Gulley, M.D., Ph.D.—recognized the complexity of the challenges facing immunotherapy today. They realized that the innovative solutions necessary to drive the field forward are, according to Hoos, “way too big a task for any individual player,” and structured the meeting accordingly, assembling one of the most diverse and well-rounded groups of experts within the oncology space. They especially emphasized the importance of collaboration.
Roy Baynes, M.D., Ph.D., Merck’s chief medical officer and global head of clinical development who also spoke at IO360, agreed.
“[Collaboration] is essential … and what’s been quite unique in this setting has been the willingness of companies to collaborate,” Baynes stressed, adding that “these are companies who traditionally have not worked together, so I think there’s recognition that working together we can actually move the science forward more quickly and that there is mutual benefit for the companies as well as for patients and for the field generally.”
Currently, the most widely successful immunotherapies belong to a class called checkpoint inhibitors, in particular those that target a pathway called PD-1. As of May 2018, five have been approved by the FDA to treat eleven different cancer types. Merck’s own PD-1 immunotherapy, pembrolizumab (Keytruda®), was even granted a historic FDA approval for patients with any type of advanced solid cancer that has an unstable genome (characterized by high microsatellite-instability, or MSI-hi).
However, PD-1 immunotherapies don’t work for the majority of patients, and are most effective in patients whose tumors have already been recognized and inflamed by T cells. In these cases, the extra boost provided by checkpoint immunotherapy can be enough to enable the tumor-targeting T cells to finish the job.
But what about patients whose tumors aren’t already recognized by the immune system? How can immunotherapy be made more effective for them?
This topic was addressed from many angles throughout IO360. Several sessions highlighted novel immunotherapies, such as targeting new checkpoints, personalized vaccines, and CAR-equipped natural killer cells. Beyond the development of new strategies, almost everyone agreed that the solution will involve combination approaches. By combining checkpoint immunotherapy with other treatments that stimulate immune responses and make cancer cells more vulnerable to immune attack, the idea is that more patients will be able to benefit from immunotherapy.
“So then,” according to Baynes, “it becomes a question of what do you combine it with? Are there ways that we could prime the T cells? Can we change the microenvironment? Can we kill a lot of cancer cells and stimulate antigen presentation? Can we try and make the cancer appear more antigenic using … a cancer vaccine or … an oncolytic [virus]?”
There are currently more than 1,400 combination immunotherapy trials that are trying to answer these questions and a major goal of these studies is to discover and validate new biomarkers to help doctors determine which patients are most likely to benefit from certain immunotherapy combinations. Biomarkers might also be able to help physicians monitor patients during treatment, allowing them to gain real-time insight into whether a certain approach is working or not, as well as determine which patients are more likely to experience side effects, providing a heads up so that they can be managed appropriately and in a timely manner.
“You know I think we’re early in this journey,” declared Baynes, adding that he expects the field “will be making progress because I do think the signs are there that we’re on a good track.”
Obviously, doctors and researchers are indispensable to this endeavor, but IO360 shined a light on other people who will be just as crucial to the field’s overall success. It was in this respect that IO360 really differentiated itself from most other cancer conferences.
By bringing together groups such as scientists, investors, and experts in clinical trial design and logistics, Baynes believed it created a “forum where indeed there’s quite a lot of folks participating who are not traditionally talking to one another on a daily basis. So I think there’s a nice opportunity for an exchange of ideas and for a fairly rich discussion.”
While many of these groups interact indirectly throughout the development of therapies, there’s one group that’s rarely brought into the fold and is conspicuously absent from many of the discussions in oncology circles: the patients themselves.
At IO360, however, it was a patient’s perspective that appeared to impact the audience most profoundly.
After a slew of chemotherapies, and with her colorectal cancer deemed inoperable, Stefanie Joho was sent home with no further treatment options. Then, she took the initiative and began educating herself about her disease. Fortunately, her sister went on the ClinicalTrials.gov database and found a PD-1 checkpoint immunotherapy trial that gave Stefanie hope.
“Then I got started on the study and within three months my tumor shrank by 65% and within a year and a few months there was no evidence of disease,” said Joho, who spoke during day two of the conference. “I’ve been feeling great ever since.”
Fortunate that she was, in her words, “brought back to life,” Joho is now committed to helping empower other patients on their journeys. She recognizes that what worked for her won’t work for everyone—her tumor, luckily, was MSI-hi, the type that checkpoint immunotherapy is especially effective against—but what she learned during her experience can still provide immense value to all sorts of patients, especially when it comes to educating themselves about their disease.
“Now, more than ever, self-education and empowerment [are] so important because the field is changing so quickly,” she said, before explaining how beneficial it is for patients to “really understand the exciting stuff that’s happening in [your cancer type], the different clinical trials … the experts and the institutions at the forefront of this.”
While the reality of cancer is understandably frightening, Joho regards her increased involvement positively. “For me, that education was a comfort. It made me feel like I was taking ownership of this disease that I felt so powerless [against].”
One particular area of patient education in which she thinks the field can make great progress has to do with the perception of (and myths surrounding) clinical trials. “It’s important for patients to understand that these aren't just scientists in a lab saying 'oh let's just throw this at patients who are at the end of the road.'"
Instead, she seeks to help patients realize that clinical trials are “incredibly well thought out hypotheses with scientific backing … that have gone through rigorous processes to even get here. So understand that clinical trials might actually be your best bet.”
Grace Cordovano, a professional patient advocate who also attended IO360, was equally passionate about this “awareness problem.”
“Most patients, when they hear clinical trial, in the context of a debilitating diagnosis, are fearful. That means there’s no hope left. I’m dying, I’m out of options. They see them as basically a Hail Mary,” Cordovano explained.” And now, she believes, “we have an opportunity through education and awareness to change that treatment paradigm as to how [clinical trials] are perceived.”
According to Joho, clinical trials also offer another potential benefit for patients.
“I, personally, have never felt more taken care of than in a clinical trial because … everybody is on the same team. Everyone is working toward the same thing. Everyone has so much at stake. Everyone cares so much.”
In addition to helping other patients, Joho stressed that patients sharing their perspectives and becoming more actively involved in the entire process can also help scientists, doctors, and drug developers in their work to advance more effective treatments.
“It’s really important for patients to know that they are an equal part of this equation … One doesn’t happen without the other. Medicine does not advance, science does not advance, without patient involvement, and patients don’t understand that.”
While she’s quite grateful for her clinical trial care, describing it as “the best care of her life,” Joho still sees improvements that can—and need to—be made. Above all, she insisted that patient feedback must be more regularly sought and incorporated.
“I never received a sheet of paper or anything that said 'How was your experience in a clinical trial? What can we do better?’ There’s so much feedback that I would want to give … I think that’s starting to change and that’s great, but there’s so much work that needs to be done in terms of involving patients in every single aspect.”
Here, too, Cordovano agreed, saying that “unifying [the perspectives of patients and doctors] could be something very powerful, so I think including that patient voice is critical even if it’s small changes. Small changes could be very profound.”
For immunotherapy to achieve its full potential, it will require more than just buy-in on the laboratory and clinical sides of things. Patients, who have the most at stake—literally their lives—must have their voices better heard. Although much work remains to be done to ensure this, acknowledging the gap and recognizing the need to bridge it is a necessary first step, and according to Joho, gathering like IO360 will be crucial to helping foster these productive partnerships.
“I left there feeling really positive. The amount of people that came up to me after being so moved by my story, who told me: 'You have re-energized me in focusing in on why I do this.' I was really inspired by that because I think it shows how much people in industry and investors also crave the patient perspective.”