Setting new standards in information exchange for the pharmaceutical and biotech industry
3rd Annual Immuno-Oncology 360° Led by Dr Axel Hoos (GSK) and Dr James Gulley (NCI)
February 9, 2017
A 360-degree approach addressing business aspects, clinical advancements and scientific data to transform the way cancer is treated.
The 3rd annual Immuno-Oncology 360° (IO360) event took place February 1-3, 2017 in NYC. Designed by lead advisors Dr Axel Hoos (GSK) and Dr James Gulley (NCI), the program provided a unique 360-degree approach addressing the most-up-to-date information regarding business aspects, clinical advancements and scientific data that helped to accelerate clinical trials and FDA approval, ultimately transforming the way cancer is treated.
Day one’s plenary sessions covered “Preclinical Science,” chaired by Dr Patrick Mayes, Director & Early Development Leader, GlaxoSmithKline and “Translational Science and New Technologies,” chaired by Dr Renee Donahue, Scientist, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute. Highlights include:
1. Can Agonist Antibodies Play a Role in Immunotherapy?
Though the concept of incorporating agonist antibodies into an immunotherapeutic treatment regimen is still a long way from durable viability, Dr Mayes shared that there is at least some reason for optimism.
“We believe that immune agonist antibodies have some significant potential and promise as cancer therapies, and I think that’s been illustrated by the explosion of agents that have entered the field in the last five years.”
Dr Mayes said developing agonist antibodies for immunotherapy presents a number of unique challenges, one of which being the elevated need for precise dose selection. “Dose level is critical when it comes to these agents,” he said. “It’s not about dosing high, it’s about finding the right dose level to achieve significant activation.”
Another issue limiting the development of viable agonist antibodies is the degree to which FcyR and IgG interactions differ between animal and human test subjects, which Dr Mayes said complicates the translation of functional data.
“It means that interpretations that we’re able to make in a mouse system or even a monkey system aren’t necessarily going to translate, since the IgG specifically is such an important characteristic for agonist antibodies. We need to be very careful about how we interpret our data.”
2. Sequencing of Combination Agents
Another emerging concept highlighted in several presentations on Wednesday was the combination of immunotherapy with certain types of chemotherapy, despite their inherent contradiction in function.
“It’s actually not as bad an idea as some might think,” said Dr Charles Drake, director of genitourinary oncology and associate director for immunotherapy at the Columbia University Medical Center’s Herbert Irving Comprehensive Cancer Center.
Dr Drake noted there is a growing body of research that suggests the addition of chemotherapy to a regimen of immunotherapeutics can improve the overall efficacy of the treatment. Exactly how successful the tactic can be may depend on how carefully timed the integration of therapies is on a repeatable basis. “Research shows that if you introduce an anti-PD1 during the initial antigen encounter right at the time the T-cell sees its target antigen, you can actually reprogram that T-cell to continue having an effect or a function further down the line, and can actually see longer survival as a result.”
3. Immunosequencing in Cancer Treatment
Dr Lanny Kirsch, SVP, Translational Medicine, Adaptive Biotechnologies, said his focus has been refining and expanding the application of immunosequencing in cancer treatment.
“In order to expand the benefit of immunotherapy to the greatest number of patients, it would be extremely useful to be able to assess the immune status of a patient and the tumor that resides inside of them. Immunosequencing is one approach to doing that. It’s the enumeration, specification and quantification of each and every B or G cell in any biological sample.”
Dr Kirsch also shared that he is particularly interested in the prospect of using immunosequencing to develop blood-borne biomarkers that could more accurately track the effects of an immunotherapy, rather than relying on biopsied tissue.
“We think that could be of significant use in the care of patients receiving immunotherapy.” “We hope we’re becoming more refined and sophisticated in terms of being able to apply a computational matrix to better extract critical information from these kinds of analyses,” Kirsch later added.
Day two featured plenary sessions on “Trends & Collaborations in the IO Space,” chaired by Dr Ramy Ibrahim, VP and Head of R&D, Parker Institute for Cancer Immunotherapy, “Clinical Advancements Part 1,” chaired by Dr James Gulley, Head, Immunotherapy Section, Director, Medical Oncology Service, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute and “Imaging Methodologies & Techniques for Immunotherapy,” chaired by Dr Andrea Perrone, Associate Vice President, Translational Medicine, Merck Research Labs. Key takeaways from day two include:
1. New Details on FNIH’s Forthcoming Partnership for Accelerating Cancer Therapies
In 2016, the Foundation for the National Institutes of Health announced plans to develop a new program under the Cancer Moonshot initiative, noting at the time the lack of cohesion within the industry when it came to generating and managing clinical data.
“We have a lot of knowledge gaps and duplicative deployment of resources, and I think we could probably do much better with a much more systematic and uniform approach, particularly in the area of biomarker development,” said David Wholley, MPhil Director, Research Partnerships Division, FNIH.
Mr Wholley hopes to eliminate those disconnects and redundancies with the launch of FNIH’s Partnership for Accelerating Cancer Therapies (PACT), which he said will establish a network of core laboratories to conduct, standardize and validate biomarker assays.
“We decided to focus our efforts on a problem that was urgent for everyone, but also tractable and highly relevant to the types of resources that NCI was already developing. The focus here is building out a more systematic and robust effort to develop and validate biomarkers for immunotherapy and, particularly, combination trials.” Assuming a successful fundraising campaign, the PACT is expected to launch in the third quarter of 2017. The partnership’s other primary objectives will include:
– Funding the development of new exploratory biomarkers and assays
– Incorporating biomarker modules into trials
– Creating a comprehensive database of biomarker module and clinical data
2. Clinical Advancements and Challenges
Dr Roy Baynes, SVP and Head, Global Clinical Development, Chief Medical Officer, Merck Research Laboratories, provided an update on expanding the approved monotherapeutic uses of PD-1 antibodies in the treatment of various cancers.
“As we look at the goal of trying to establish PD-1 as being transformational in cancer, I believe we are making fairly good progress,” Dr Baynes said.
Having already established its PD-1 antibody Keytruda as a standard-of-care monotherapy for advanced melanoma, Dr Baynes said Merck recently achieved global approval for PDL-1 high front-line and PDL-1 positive second-line lung cancer patients. The company has also gained approval for its PD-1 antibody in the treatment of head and neck cancer, and is under priority review for indications within Hodgkin’s Lymphoma and MSI-H cancer. Additionally, Dr Baynes said Merck is exploring recent positive clinical outcomes in the treatment of first- and second-line bladder cancer.
Dr Baynes also participated in a panel discussion moderated by Dr Gulley, also including Dr Alessandra Cesano, Chief Medical Officer, nanoString Technologies, Dr Patrick Hwu, Head, Division of Cancer Medicine/ Department Chair, Melanoma Medical Oncology/ Department Chair, Sarcoma Medical Oncology, MD Anderson Cancer Center and Robert Millham, MS, MSc, PharmMed SVP & General Manager, Hematology & Oncology, inVentiv Health. The panel focused on key clinical challenges facing the IO field and addressed increasing the rate of patient responses to immunotherapy, refining the field’s approach to combination therapies, reducing the risk of toxicity in combination trials and establishing a uniform system of generating, collecting and managing clinical data.
3. New Modifications to RECIST 1.1 for Immunotherapeutics
Dr Elisabeth de Vries, Professor, Medical Oncology, University Medical Centre Groningen, outlined the RECIST Working Group’s recommendations for a new guideline for imaging data collection and management in clinical immunotherapy trials, dubbed iRECIST.
“The rationale for developing iRECIST was the fact that we know that there is an atypical pattern of response in multiple immunotherapy trials, but the true frequency is unknown,” Dr de Vries said. “We also know that there are different interpretations of immune response criteria across trials, which makes it very difficult to compare the trials.”
Primary among the changes proposed under the iRECIST guideline is the difference in time point response after a RECIST 1.1 progressive disease identification. The first RECIST 1.1 progressive disease would be termed an “unconfirmed” progressive disease and must be confirmed at the next assessment 4-8 weeks afterward. Also, the time point for tumor response would be dynamic and based on a change from baseline or from nadir, as well as the last I-response. Dr de Vries said the full iRECIST guideline will be published later this year in Lancet Oncology. Dr Patricia Keegan, Director, Division of Oncology Products 2 (DOP2), OHOP, OND, CDER, FDA, said the FDA will continue to use RECIST 1.1 as the primary criteria for tumor-based endpoint imaging, but that she was “very eager to see how this plays out, in terms of whether this criteria or something based on it, would provide better information and better correlate to clinical outcomes.”
Day three concluded the conference with plenary sessions, “Business Aspects of Immuno-Oncology,” chaired by Mark Simon, MBA, Partner, Torreya Partners and “Clinical Advancements Part 2,” chaired by Dr Jeffrey Legos, SVP, Oncology Global Development & Medical Affairs, Novartis Pharmaceuticals.
1. Improving Patient Experiences in Clinical Trials
Based on his own experiences finding, joining and completing clinical trials in immunotherapy, T.J. Sharpe’s (Melanoma Survivor, Patient Advocate and Cancer Blogger) keynote address implored physicians in the IO field to find ways of making the clinical trial process easier for patients. Diagnosed with Stage 4 melanoma in August 2012, Mr Sharpe said he only knew to inquire about the possibility of joining a clinical trial because of prior professional experience and a network of contacts in the pharmaceutical industry.
“Patients don’t always know to look for different treatments, particularly immunotherapy trials. I was able to find a trial because I had a lot going for me.”
Though grateful for the PD-1 treatments that to-date have aided in an 85% reduction in measurable tumor burden, T.J. said the process of obtaining those treatments is fraught with complexity and bureaucracy, which many cancer patients may find discouraging or prohibitively difficult to navigate.
“It might just be a document to you, but it’s my life,” Sharpe said. “The average contract for a clinical trial takes about 18 weeks to execute. That’s more than 3,100 melanoma patients who will die the next time a contract goes from beginning to end. I know we can’t save all of them, but how many T.J.’s are out there trying to get into your trial to try your new therapy and are waiting for a piece of paper to be signed?”
2. The Growing Need for New Reimbursement Models
As public and political pressures mount on the pharmaceutical industry over the rising cost of specialty drugs, it is critical that the industry work with healthcare payers and providers to develop new reimbursement models for high-cost curative therapies, according to Dr Lindee Goh, Partner at Tapestry Networks.
“Developing a drug isn’t very helpful if there isn’t market access to that drug,” Dr Goh said. “If patients can’t get it because they can’t afford it, then the innovation is wasted and patient lives are left at risk.”
Dr Goh outlined several potentially sustainable reimbursement models that could ease the financial pressure on patients, including rebates, amortization, payer-backed annuities, reinsurance and government-issued bonds. However, reaching a consensus on new systems of reimbursement will require a concerted and collaborative effort among stakeholders in the healthcare industry, considering the multitude of regulatory, political and economic challenges that must be addressed.
“There’s been a lack of leadership across the stakeholder groups,” Dr Goh noted. “There isn’t any clear industry champion saying that they want to change the model, and there’s a lot of political downside to being a lead in this area.”
3. Talent Management Issues in the IO Space
Adam Millinger, Founding Partner, ProMotion Career Management, described the competition for talent in the IO field as an “arms race” fueled not only by a shortage of qualified candidates, but also systemic shortfalls in talent management strategies within the industry.
“It will come as no surprise that there’s a big gap between supply and demand for talent. [The IO space] is a new area, and as much as people are being trained, there just aren’t enough folks out there at the moment,” Mr Millinger said. “What you also have is the group that rode in on the early wave of IO that are now extremely senior within the industry, and the less-seasoned people coming in aren’t able to fill that mid-level gap.”
Mr Millinger noted other contributing factors to the IO field’s talent shortage include a reticence among traditional oncologists to learn a new discipline and companies’ weakened ability to negotiate salaries and titles with those who do have the requisite experience. As difficult as the competition for qualified talent can be, Mr Millinger thinks the industry’s larger problem appears to be retaining the talent they are able to attract, due primarily to a misalignment of motivations among new hires and executive-level management, as well as a lack of proactive career development and succession planning.
“For the people in the trenches doing the work, there’s a strong feeling that IO is a harsh, unforgiving space where companies are really pushing people to their stress limits,” Millinger said. Executives, on the other hand, are stuck in a “mercenary mindset, where they think that people who do have the experience are taking advantage and chasing titles and paychecks.” “There needs to be a better alignment of people and motivations to actual outcomes,” he added.
The Conference Forum will present the next program in the IO space, the 2nd annual Rational Combinations 360°, on June 28-29, 2017, at The New York Academy of Medicine in New York City. Designed by lead advisors Dr Axel Hoos (GSK), Dr Ian McCaffery (Corvus Pharmaceuticals) and Dr Patrick Hwu (MD Anderson), #IOCombos360 provides the most up-to-date progress on combination developments from business aspects, clinical advancements and scientific data that will help prioritize the best cancer treatments for individual patients and tumor types. Register here.
Save the date for 4th Annual Immuno-Oncology 360° in NYC, to be held February 7-9, 2018, in NYC.