[ad_1]
The novel conjugate trastuzumab duocarmazine, an antibody-drug conjugate, showed promising clinical activity and was reasonably well tolerated in an early-phase trial in patients with metastatic cancer expressing HER2 highly pre-treated, including cancer. bad.
"HER2-positive metastatic bad cancer is still incurable and the eventual development of resistance to [HER2-targeted] the treatments are almost inevitable, "wrote the authors of the study led by Udai Banerji, MD, of the Cancer Institute and Royal Marsden in London. "New drugs that also target low-HER2 expression cancers will address an unmet need in many types of tumors."
Trastuzumab duocarmazine combines trastuzumab with a binding agent containing duocarmycin. In preclinical research, the conjugate has shown promising antitumor activity in bad, ovarian and other cancers with varying levels of HER2 expression.
The researchers conducted a Phase I dose-escalation trial in 39 patients and a dose-expansion phase involving 146 other patients. The progressive dose portion included patients with metastatic solid tumors with variable HER2 status, refractory to conventional therapies; the expansion phase included patients with bad cancer (99 patients, 50 patients with HER2-positive disease), gastric (17 patients), urothelial (16 patients) and endometrial (14 patients) cancers. The results of the study were published in Oncology Lancet.
Included patients were heavily pretreated, with an average of 5.2 prior treatment lines. Most patients with HER2-positive bad cancer had received trastuzumab emtansine (80%). The complete cohort was followed for a median of 5.0 months.
The dose escalation phase of the trial gave a recommended dose of 1.2 mg / kg in phase II. During the expansion phase, treatment-related serious adverse events (AEs) occurred in 11% of patients; these included reactions related to infusion (1%) and dyspnea (1%).
The most common treatment-related adverse events, regardless of grade, included fatigue (33%), conjunctivitis (31%), and dry eye (31%). Ocular AEs were reported in 71% of cases.
The agent has shown a promising clinical activity. Of 48 evaluable patients with HER2-positive bad cancer, 16 achieved a partial objective response (33%). Notably, 9 patients (28%) with HER2-low bad cancer, hormone receptor receptor (HR) and 6 patients (40%) with HER2-low HR-negative disease also got an objective answer.
A patient with stomach cancer (6%), 4 of a urothelial cancer (25%) and 5 patients with cancer of the stomach. endometrium (39%) also got an answer.
"This phase I trial of trastartumab trocartin demonstrated significant and relevant clinical activity as well as a manageable safety profile in pretreated patients with metastatic HER2-expressing cancer, including bad cancer." bad trastuzumab resistant to emtansine and HER2-weak, "concluded the authors. Trastuzumab duocarmazine is currently being tested against the physician's choice for metastatic bad cancer in the TULIP Phase III trial.
In an accompanying editorial led by Xavier Pivot, MD, PhD, of the Paul Strauss Cancer Center in Strasbourg, experts noted that a number of antibody-drug conjugates involving trastuzumab were under development. because its chemical composition makes it possible to bind a cytotoxic agent without affecting its HER2 binding capacity. "The encouraging results of this first human study of this new drug support the idea that the family of antibody-drug conjugates could serve as new agents with many modalities of anticancer activity, thus allowing many new cancer treatment strategies. cancer, "they wrote.
Source link
