#ASCO21: Eli Lilly-partnered Merus reveals new data for NRG1 fusion cancers including pancreatic and NSCLC
One of Eli Lilly’s newest R&D partners revealed some new data at #ASCO21 for an in-house program, and it’s one that could cover a broad range of solid tumors with rare genetic mutations.
The Dutch biotech Merus NV reported that their experimental drug zenocutuzumab, referred to as “zeno,” induced partial responses in 13 of 45 patients with NRG1 fusion-positive cancers as of April 13 cutoff date, good for an overall response rate of 29%. Merus is evaluating the candidate in a single-arm Phase I/II study with 61 enrolled patients.
Notably, 12 of the evaluable patients came into the trial with NRG1 positive pancreatic cancer, with five seeing confirmed partial responses.
Merus also looked at patients with NRG1 positive non-small cell lung cancer, observing that six of 24 such patients achieved partial responses by the cutoff. The biotech noted that a seventh patient here reached partial response after the cutoff date as well.
Nine other patients with other undisclosed NRG1 positive cancers reached the evaluable stage by April 13, with two hitting a partial response. The full trial population enrolled with a median of two prior lines of therapy, and research has suggested the mutation is typically associated with a poorer prognosis relative to other cancer patients.
CEO Bill Lundberg told Endpoints News that the number of cancer patients whose tumors have such mutations is relatively small. In pancreatic cancer, NRG1 fusion-positive mutations make up about 0.5% to 1.5% of tumors, while in NSCLC they account for anywhere between 0.3% and 3%.
Even though lung and pancreatic cancers are vastly different, Lundberg said the NRG1 mutation can occur in the epithelial cells lining both organs.
“It’s turned out over the years that the drivers of cancer can be similar regardless of whether it’s in an epithelial cell in the pancreas or an epithelial cell in the lung,” Lundberg said. “And there have been a number of these cancer driver mutations, whether it’s a RAF driver, for which a drug just got approved a week ago, or it’s these NTRK fusions, or RET or ROS mutations.”
NRG1 mutations occur when one part of the chromosome is “lopped” onto another part of the DNA, Lundberg added. It’s a normal ligand for the HER3 protein and binds to it, allowing the protein to further bind to HER2. Zeno, then, functions by binding to both HER2 and HER3, preventing HER3 from spurring the mutation and specifically blocking the ligand.
Lundberg is keeping his cards close to the vest regarding when Merus would be ready to submit an application to the FDA. He wouldn’t put a timeline on when the Phase I/II might be completed, only saying that other companies with similarly targeted programs have a trial size of about 55 patients.
Merus will continue to enroll patients in its clinical programs even after heading to the FDA, whenever that might be, Lundberg noted. He also demurred about advancing the program into a late-stage trial, again comparing zeno to how similar programs achieved approval based on one single-arm study.
On the whole, though, the data come as Merus’ partnership with Lilly gets into full swing. Back in January, Lilly paid $40 million in upfront cash and $20 million in an equity stake to co-develop three bispecific antibodies looking to engage the CD3 antigen on T cells. Each program could net up to $540 million in development and sales, bringing the total value of the deal north of $1.6 billion.