Zenocutuzumab exhibits efficacy in NRG1 fusion-positive cancers
Key takeaways:
- Nearly one-third of the primary efficacy population responded to zenocutuzumab.
- The drug exhibited particularly strong activity among people with lung or pancreatic cancers.
Zenocutuzumab exhibited efficacy among patients with NRG1 fusion-positive cancers, according to phase 2 data published in The New England Journal of Medicine.
Nearly one-third of the cohort — which included patients with multiple tumor types — responded to therapy. Those with non-small cell lung cancer and pancreatic cancer derived the most benefit.
“We hoped and expected that zenocutuzumab would be effective in patients with NRG1-positive cancers; however, it was nonetheless very exciting to see these results,” Alison M. Schram, MD, gynecologic medical oncologist and early drug development specialist with Memorial Sloan Kettering Cancer Center, told Healio. “What was most surprising to me was the near immediate improvement in cancer-related symptoms observed in some patients, and the exceptional tolerability of the regimen.”
Neuregulin 1 (NRG1) fusions are recurrent oncogenic drivers found in multiple solid tumor types. NRG1 binds to HER3, which “leads to heterodimerization with HER2 and activation of downstream growth and proliferation pathways,” researchers wrote.
Schram and colleagues conducted the open-label, phase 2 eNRGy study to assess the efficacy and safety of zenocutuzumab (Bizengri, Merus N.V.) for patients with advanced NRG1 fusion-positive cancer.
The study included 204 adults with 12 different tumor types.
All patients received 750 mg IV zenocutuzumab once every 2 weeks.
Overall response rate — including complete or partial responses — according to investigator assessment served as the primary endpoint. Secondary endpoints included duration of response, PFS and safety.
Researchers excluded 43 patients from the primary efficacy analysis, largely due to them taking their first dose less than 24 weeks prior to data cut-off.
Of the 161 patients (median age, 62 years; range 21-88) in the efficacy assessment, 158 patients had measurable disease.
Nearly one-third 30% (95% CI, 23-37) of those with measurable disease responded to treatment.
Median duration of response reached 11.1 months (95% CI, 7.4-12.9), with 19% of responses ongoing at data cutoff.
Researchers observed responses in multiple tumor types, including among 27 of 93 (29%; 95% CI, 20-39) patients with NSCLC and 15 of 36 (42%; 95% CI, 25-59) patients with pancreatic cancer.
Median PFS in the primary efficacy population reached 6.8 months (95% CI, 5.5-9.1).
The most common therapy-related adverse events included diarrhea (18%), fatigue (12%) and nausea (11%). Fourteen percent had infusion-related reactions.
A single patient discontinued treatment due to a treatment-related adverse event.
“Based on the results of this study, zenocutuzumab was FDA approved for patients with advanced, unresectable or metastatic non-small cell lung cancer or pancreatic adenocarcinoma harboring an NRG1 gene fusion with disease progression on or after prior systemic therapy,” Schram told Healio. “The immediate clinical implication is that patients eligible for zenocutuzumab should be considered for this therapy. Importantly, NRG1 fusions can be difficult to detect on DNA-based sequencing, and it is critical that clinicians do RNA sequencing in driver-negative cancers.
“Potential next steps include further exploring targeted therapy in non-lung and pancreatic cancers with NRG1 fusions,” she added. “Additionally, other methods to target NRG1 fusion-positive cancers should be explored to potentially provide more than one treatment option for patients with NRG1-positive cancers, such as small molecule inhibitors.”
For more information:
Alison M. Schram, MD, can be reached at schrama@mskcc.org.
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