Date: 2016-10-07
Type of information: Presentation of results at a congress
phase: 1
Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 2016 Congress
Company: Seattle Genetics (USA - WA), a wholly owned subsidiary of Takeda Pharmaceutical (Japan) Agensys, an affiliate of Astellas (Japan)
Product: ASG-15ME
Action
mechanism: monoclonal antibody/antibody drug conjugate (ADC). ASG-15ME is an antibody-drug conjugate (ADC) targeting SLITRK6. SLITRK6 is found in urothelial cancer and other cancers, including lung, breast and glioblastoma. The antibody is also attached to monomethyl auristatin E (MMAE), via an enzyme-cleavable linker using Seattle Genetics' proprietary technology.
Disease: previously treated metastatic urothelial cancer
Therapeutic area: Cancer - Oncology
Country:
Trial
details: monoclonal antibody/antibody drug conjugate (ADC). ASG-15ME is an antibody-drug conjugate (ADC) targeting SLITRK6. SLITRK6 is found in urothelial cancer and other cancers, including lung, breast and glioblastoma. The antibody is also attached to monomethyl auristatin E (MMAE), via an enzyme-cleavable linker using Seattle Genetics' proprietary technology.
Latest
news: * On October 7, 2016, Seattle Genetics and Agensys, an affiliate of Astellas, presented updated clinical data for ASG-15ME at the European Society for Medical Oncology (ESMO) Congress . ASG-15ME is an investigational antibody-drug conjugate (ADCs) that target the cell surface protein SLITRK6. The clinical data continue to demonstrate overall response rates in patients with previously treated metastatic urothelial cancer, including those with prior checkpoint inhibitors. Safety and recommended phase 2 doses were also presented. While the phase 1 study will continue to enroll patients, evaluation of next developmental steps for ASG-15ME is ongoing. Of the 48 patients evaluable for response, 18 patients (38 percent) had an objective response, including one patient (two percent) who achieved a complete response and 17 patients (35 percent) who achieved a partial response. The preliminary estimate of median progression-free survival is 16.1 weeks.
Interim Analysis of a Phase 1 Dose Escalation Trial of the Antibody-Drug Conjugate (ADC) AGS15E (ASG-15ME) in Patients (Pts) with Metastatic Urothelial Cancer (mUC) (Abstract #780PD, poster presentation with discussion on Sunday, October 9, 2016): Data were reported from 54 patients with metastatic urothelial cancer having a median age of 64 years. Of these patients, 52 patients (96 percent) had previously undergone treatment with a platinum-based chemotherapy regimen and 17 patients (32 percent) had progressed on or after treatment with checkpoint inhibitors. Thirty patients (56 percent) had received two or more prior systemic therapies. The primary endpoints of the ongoing clinical trial are to evaluate the pharmacokinetics and safety of ASG-15ME as a monotherapy at escalating doses of 0.1 to 1.25 mg/kg weekly for three of every four week cycles. In addition, the trial is evaluating antitumor activity, objective response rate and disease control rate. Key findings include:
The recommended phase 2 dose is 1.0 mg/kg. In 20 patients treated at the 1.0 mg/kg dose level, 10 patients (50 percent) had an objective response, including one patient (five percent) who achieved a complete response and nine patients (45 percent) who achieved a partial response. Disease control was achieved for 14 patients (70 percent), defined as achieving complete response, partial response or stable disease.
Of the 14 patients across dose levels who had previously been treated with checkpoint inhibitors, six patients (43 percent) achieved a partial response. At the recommended phase 2 dose, three out of seven patients (43 percent) previously treated with checkpoint inhibitors achieved a partial response.
In the 13 patients whose cancer had metastasized to the liver, which typically has a poor prognosis, six patients (46 percent) achieved an objective response. Of 22 patients previously treated with taxanes, nine (41 percent) achieved an objective response.
The most common treatment related adverse events of any grade occurring in 20 percent or more of patients were fatigue (44 percent), nausea (22 percent) and decreased appetite (20 percent).
Fourteen patients (26 percent) experienced ocular adverse events and six patients (11 percent) developed ocular symptoms with corneal abnormalities at the recommended phase 2 dose. All events resolved with appropriate management.
Enrollment is ongoing at 1.0 mg/kg and the study has been amended to include a checkpoint inhibitor-treated cohort to further understand safety and activity in this population.
