There are days when it seems the pharma universe turns around combination immuno-oncology therapy, that it is the only drug discovery and development activity. The first results that seem to present a real cure for some cancers have stirred an enthusiasm not typically linked to the pharma industry, the creation of atypical collaborations among major players, and a land rush towards opportunities to trial new combinations of checkpoint inhibitors and agents to target diverse tumor types.
For BIO-Europe® 2015, key players in this fast-advancing field gathered for a panel discussion led by moderator Beatrice Gerard, VP for Strategic Drug Development at Quintiles. After setting the context for discussion, she posed a rapid series of questions that reflect the complexity of challenges facing the industry in immuno-oncology, and provoked a roundtable discussion. With the plethora of possible combinations, what can be combined, when to combine it, how to combine it, for which patients, and how can it be validated before going to trial?
: From left, Mohamed Ragab, Philippe Lopes-Fernandes, Iain Dukes and Michel Detheux
The Senior VP for Business Development and Licensing with MSD, Iain Dukes noted that his company was the first to demonstrate success for a checkpoint inhibitor in patients with melanoma and the inhibitor has since been approved for non-small cell lung cancer. Currently, he said, MSD has more than 16 ongoing registration studies and the most extensive mono-agent program of any pharma company working in this space.
MSD has also formed more than 20 collaborations in the hunt for valid combinations, he said, and it is significant that the majority of these partnering programs have no strings attached. “We’ll kick that rock down the road until we see if it works or doesn’t work,” he said.
Yet he cautioned that “we need to step back on the premise of testing all these combinations, because to date there is not really evidence that combination therapies are working. In melanoma there is an argument that there is a synergy with PD-1. Outside the realm of melanoma, we are not certain where these checkpoint inhibitors will actually work. We will have to see in the next few quarters when the data comes out with these agents to see how well they actually work.
“In terms of predicting combinations,” he said, “preclinical models are fairly useless, because for all these potential agents, it can be shown they will synergize for PD-1.”
On this point Mohamed Ragab, VP for Oncology Search and Evaluation with Bristol-Myers Squibb suggested that “preclinical models have improved dramatically in recent years. I do agree that there is a lot of data there that would not translate into humans. Yet what needs to be done is to take the preponderance of evidence whether from preclinical, the biology, or the human biomarkers, and here the preclinical data is the most important and the most relevant. You have to use every bit and piece of evidence to build a picture of what is the most likely successful combination in order to really focus on the few that have the best chance for success.”
While Bristol-Myers Squibb has a strong portfolio of products in immuno-oncology, he said that in the past two years the company has formed 15 collaborations and several partnerships in the field.
“Some partnerships are exclusive, though most of our collaborations in this space are not exclusive,” he said. “What is important is a collaboration based on the best science to achieve the best outcomes for that science to create something that is meaningful for the patient at the end of the day.”
The Senior VP for Global Licensing and Business Development at Merck Serono, Philippe Lopes-Fernandes reviewed deals his company has entered in order to tap the potential for combining agents with checkpoint inhibitors, including the collaboration with Pfizer last year for PD-L1.
This field is moving fast, and it is exciting, he acknowledged, referring to a map plotting more than 80 programs across the industry that are currently underway using PD-1 and PD-L1. Yet these are the obvious starters, the low-hanging fruit, he said.
“As we move away from the late stage of development, we are going to see many more novel models for earlier stage programs, for novel agents that could be combinable,” he suggested, adding that “at some point we are going to see novel-novel-novel combinations such that it is going to be very interesting to see the landscape in two years.”
Building on an agreement that PD-1 will serve as a backbone for development programs for the coming decade, panel moderator Gerard concluded saying the paradigm shift has brought exciting results already.
“This is the first time we have seen a cure for metastatic patients, and it is amazing,” she said. “We are just beginning, affecting 20% of patients, yet if finding new combinations can raise this to 40% and then on to 60% of patients, this will bring a major change.”