Zenocutuzumab induced clinically meaningful antitumor activity and showed a favorable safety profile in patients with advanced NRG1-positive cholangiocarcinoma, according to findings from the phase II eNRGy trial published in the Journal of Clinical Oncology.
“Second-line chemotherapy is only modestly effective for most patients with this disease, and we greatly need better treatment options,” said lead study author James M. Cleary, MD, PhD, a medical oncologist and the Co-Director of Clinical Trials in the Center for Gastrointestinal Oncology at Dana-Farber Cancer Center. “Compared to what we typically observe with standard chemotherapy, zenocutuzumab doubles the duration of clinical benefit. In addition, since the therapy is well tolerated, it is a significant step forward in terms of quality of life.”
Background and Study Methods
Zenocutuzumab is a HER2 x HER3 bispecific antibody that has already been approved for use in previously treated patients with advanced/metastatic NRG1-positive non–small cell lung cancer and pancreatic adenocarcinoma.
The single-arm, multicenter, global phase II eNRGy trial evaluated the use of zenocutuzumab in patients with solid tumors harboring NRG1 gene fusions, including 22 patients with cholangiocarcinoma. Earlier findings from the study led to the recent U.S. Food and Drug Administration approval for zenocutuzumab for patients with advanced, unresectable, or metastatic NRG1-positive cholangiocarcinoma who experience disease progression on or after a prior systemic therapy.
Key Findings
Updated findings for the cholangiocarcinoma group in the eNRGy trial showed that three patients did not meet the protocol-defined criteria for being included in the efficacy analysis.
Seven of 19 eligible patients achieved a response to zenocutuzumab. The objective response rate was 36.8% (95% confidence interval [CI] = 16.3%–61.6%), and the clinical benefit rate was 57.9% (95% CI = 33.5%–79.7%).
The median duration of response was 7.4 months and the median time to response was 1.9 months. The median progression-free survival was 9.2 months (95% CI = 3.9–11.1 months).
The majority of treatment-related adverse events were grade 1 or 2; the most common events were diarrhea in 27.3% of patients, fatigue in 18.2%, and nausea in 13.6%. One grade 3 anemia event was reported. No patients discontinued treatment due to a treatment-related adverse event.
“It is increasingly important that we do the right tests for our patients, which includes doing RNA and DNA testing for patients with cholangiocarcinoma,” Dr. Cleary added “We are worried that patients might miss out on a chance to benefit from novel precision medicines. We are so grateful to the patients from around the world who participated in this trial and want as many patients as possible to benefit from these findings in the future.”
DISCLOSURES: For full disclosures of the study authors, visit ascopubs.org.
