Merus charts early promise for cancer drug targeting NRG1 fusions

Cancer in newspaper clipping
NRG1 fusions are rare, but they can drive several types of cancer. Merus is betting that its NRG1-targeted drug will make a difference for patients with the abnormality. (PDPics/Pixabay)

Netherlands-based Merus initially set out to study its bispecific antibody zenocutuzumab in solid tumors, but it revised those plans this summer in light of data showing the drug’s efficacy in targeting a rare but aggressive gene abnormality. Now, the company says it has strong evidence it’s on the right path—though, admittedly, it’s very early evidence.

Zenocutuzumab (also called MCLA-128) targets fusions involving the gene NRG1, which can drive the growth of many different types of cancers. The drug was being studied in one trial in metastatic breast cancer and another in solid tumors, but before the company refocused the trial on tumors with NRG1 fusions, three patients who tested positive for the abnormality were treated with the drug via an early-access program.

Targeting NRG1 fusions with the investigational drug produced tumor shrinkage in two of the patients, both of whom had pancreatic ductal adenocarcinoma, and in another with non-small cell lung cancer. The data were presented by investigators from Memorial Sloan Kettering Cancer Center at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.

Zenocutuzumab was designed to work in two different ways: One part of the drug blocks the interaction between the cancer-driving proteins HER2 and HER3. Another arm of the drug blocks NRG1 fusions so they can’t activate HER3.

One patient with pancreatic cancer who received zenocutuzumab saw tumor shrinkage of 54% at five months, the investigators said. In the second pancreatic cancer patient, the cancer showed a 25% reduction in size at five months, and the disease was deemed stable. The lung cancer patient, who had progressed following six previous treatments, showed a 41% reduction in tumor size after five months. All three patients are still taking zenocutuzumab.

“These early data have given us further affirmation for focusing our efforts moving forward” with the revised trial, said Merus CEO Ton Logtenberg, Ph.D., in a conference call with investors Monday. “Hopefully this early evidence of clinical activity encourages our clinical investigators to consider [the trial] when an NRG1 fusion patient is identified through their preferred molecular profiling method.”

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At the AACR-NCI-EORTC meeting, Merus said it would not advance to a phase 3 trial in breast cancer but instead would focus on continuing to assess the drug in the treatment of NRG1-fusion-positive solid tumors. The company had announced in June that it amended the solid-tumor trial to only include patients with tumors that tested positive for the fusion.

NRG1 fusions are rare; Merus estimates they occur in 3% of non-small cell lung cancer patients, 1.5% of pancreatic cancer cases and less than 1% of all other cancer types.

That said, targeting rare genetic abnormalities can be a good business strategy, as proven by Bayer’s Vitrakvi, approved by the FDA late last year to treat any cancer with TRK fusions. Analysts estimate sales of the drug could eventually hit $850 million per year.

Merus attracted some buzz a few years back with its impressive list of big-named backers, which included Novartis, Johnson & Johnson and Pfizer. It had to dial down its plan to raise $100 million in an initial public offering but still managed to pull in $55 million in May 2016. Later that year, it inked a $200 million deal with Incyte to develop bispecific antibodies.

During the conference call, one analyst asked if Merus has a good handle on why some patients with NRG1 fusions do better on zenocutuzumab than others. He wondered, could other genetic abnormalities be present that could make patients resistant to the drug, even if they have an NRG1 fusion? Logtenberg acknowledged that the impact of other cancer-promoting genes on the efficacy of the drug has yet to be determined.

In lung cancer in particular, “fully understanding the genomic mutational status of these patients will be imperative going forward to understand why certain patients will have responses and other have not,” Logtenberg said. “That’s obviously a work in progress.”

The trial of zenocutuzumab in solid tumor patients with NRG1 fusions will enroll 250 patients and is estimated to finish in late 2022.