After the first positive signals emerged from the phase I/II trial evaluating the combination of Incyte's selective IDO1 inhibitor (epacadostat;INCB024360) with Merck's PD-1 inhibitor (pembrolizumab), the partners moved quickly into a phase III study. And now, the first patients with treatment-naïve advanced melanoma are being treated in the pivotal ECHO-301/Keynote-252 phase III study. This dynamic collaboration has been fast-paced from the start.
To build on the initial success of checkpoint inhibitors as cancer therapeutics and based on exciting pre-clinical data, Incyte began seeking a partner that could help. "It became clear to Incyte that future combination studies for epacadostat should include an anti-PD-1. The potential of novel immune therapy combinations to advance the field was evident." says Lance Leopold, MD, group vice president, immuno-oncology development at Incyte.
When Incyte began speaking to potential partners, Merck stood out."While meeting with Merck, we were struck by how quickly they recognized the potential of the partnership and also how quickly the discussions moved forward. It was clear the collaboration was a priority for Merck. And, their level of interest translated throughout the whole organization - licensing, legal and so forth," Leopold says.
“We work as though a patient is looking over our shoulders saying, 'You know, tomorrow isn't good enough!'”
Since 2014, when Merck's PD-1 inhibitor was approved by the FDA for advanced melanoma, Merck has been on a fast-track to hunt for drugs that can be used in combination to boost the drug's response rate. Incyte's IDO1 inhibitor targets an enzyme that depletes the essential amino acid tryptophan in the tumor microenvironment and allows some tumors to escape immune surveillance. By exploiting the IDO1 pathway, Incyte's compound in combination with other immunotherapy compounds may "uncloak" these tumors and allow the immune system to do its natural job of fighting the tumor.
Merck's interest in Incyte's IDO1 compound is part of a larger commitment to accelerating its immuno-oncology programs. Since its PD-1 inhibitor was first studied in melanoma, Merck's immunotherapy clinical program has expanded into more than 100 combination trials and 30 additional types of cancers, with dedicated development teams at the core of these research efforts. Partners like Incyte are essential to Merck's fast-growing program to pursue the full potential of this expanding science.
From the start, the partners were in total agreement of the urgency of the task. "We work as though a patient is looking over our shoulders saying, 'You know, tomorrow isn't good enough!'" says Leopold. That has set the tone for the Merck/Incyte partnership. Scot Ebbinghaus, a distinguished scientist at Merck and senior member of the collaboration team, agrees. "The team at Incyte has been a really fantastic partner and this collaboration exemplifies the way a good partnership should work. Both sides understand there is no time for prolonged development," says Ebbinghaus. And that sense of urgency means both companies have to be decisive, nimble and willing to consider taking the risk of making decisions based on small amounts of data - trusting the other to be flexible if changes are needed.
Early on the partners faced a major decision related to the trial design in order to allow for the evaluation of multiple tumor types. "When we recognized we had a problem to resolve, we worked right through it," says Leopold. "It's to everyone's credit that they could get behind such an important shift so quickly."
With the expansion of the relationship to include a phase III study, once again, both companies showed flexibility and a deep commitment to the collaboration. Even before the agreement was signed, Incyte, working on good faith, began developing the protocol. Everyone—the biomarker and the joint study teams—began working on logistics. "Merck is operationalizing the phase III study and has so far met or exceeded all projections as a testimony to our sense of urgency," says Ebbinghaus. Both partners agree the team is laser focused.
"While our understanding of the immune system and how it's regulated has been revolutionized over the last 10 years, we are learning more every day. We're working in an area that deeply impacts people's lives," says Leopold. "Every day counts."