Date: 2017-06-05
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: enfortumab vedotin (ASG-22ME)
Action
mechanism:
- monoclonal antibody/antibody drug conjugate (ADC). Enfortumab vedotin (ASG-22ME) is an antibody-drug conjugate (ADC) targeting Nectin-4, which can be found on multiple cancers, including urothelial, breast, lung and pancreatic. The antibody is attached to a synthetic cytotoxic agent, 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: Canada, USA
Trial
details: The purpose of this study is to evaluate the safety and pharmacokinetics ASG-22CE as well as assess the immunogenicity and antitumor activity in subjects with metastatic urothelial cancer and other malignant solid tumors. (NCT02091999)
Latest
news:
- • On June 5, 2017, Seattle Genetics and Astellas highlighted updated phase 1 data for enfortumab vedotin (ASG-22ME) studied as monotherapy treatment for metastatic urothelial cancer (mUC) at the American Society of Clinical Oncology (ASCO) 52nd Annual Meeting in Chicago. The ongoing trial is evaluating the safety and anti-tumor activity of enfortumab vedotin at escalating doses of 0.5 to 1.25 milligrams per kilogram (mg/kg) weekly for three of every four week cycles. Data were reported from 81 patients diagnosed with mUC and a median age of 67 years. Of these patients, 37 (46 percent) were previously treated with CPIs and 77 (95 percent) had undergone treatment with a platinum-based chemotherapy. Ninety-seven percent of patient screening samples showed Nectin-4 expression, the majority of which were at a high level. All response rates include confirmed and unconfirmed responses, as assessed by the investigator. The recommended phase 2 dose (RP2D) has been established at 1.25 mg/kg. Key findings include:
- Of the 71 patients evaluated for response, 29 patients (41 percent) had an objective response, including three (four percent) complete responses and 26 (37 percent) partial responses. Disease control was achieved in 51 patients (72 percent), defined as the sum of patients achieving complete responses, partial responses or stable disease. The preliminary estimate of median duration of response for all patients was 24 weeks.
- In 30 patients treated at the RP2D level, 16 patients (53 percent) had an objective response, including one (three percent) complete response and 15 (50 percent) partial responses. Disease control was achieved for 22 patients (73 percent).
- Of the 32 patients previously treated with CPIs and evaluated for response, 14 patients (44 percent) had an objective response, including one complete response (three percent) and 13 (41 percent) partial responses. At the RP2D, eight out of 17 CPI-treated patients (47 percent) achieved a partial response, and disease control occurred in 13 patients (77 percent).
- Of the 19 patients with liver metastases, nine (47 percent) had an objective response, including one (five percent) complete response and eight (42 percent) partial responses. Disease control was achieved for 13 patients (68 percent).
- The most common treatment-related adverse events of any grade occurring in 10 percent or more of patients were nausea (36 percent), pruritus (31 percent), fatigue (30 percent) and diarrhea (28 percent). The most common Grade 3 or 4 adverse events occurring in five percent or more of patients, regardless of attribution, were urinary tract infections, hypophosphatemia, hyponatremia and anemia.
More information about this clinical trial (NCT02091999), including enrolling centers, is available by visiting www.clinicaltrials.gov.
- • On October 7, 2016, Seattle Genetics and Agensys, an affiliate of Astellas, presented updated clinical data for enfortumab vedotin (ASG-22ME) at the European Society for Medical Oncology (ESMO) Congress . Enfortumab vedotin is an investigational antibody-drug conjugate (ADCs) that target the cell surface proteins Nectin-4. 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 for this program. While the phase 1 study will continue to enroll patients, the companies plan to advance enfortumab vedotin and discuss next steps with regulatory agencies. Interim data from phase 1 dose-escalation study of enfortumab vedotin monotherapy in patients with metastatic urothelial cancer will be presented at the ESMO Congress during poster sessions on Sunday, October 9, 2016. The clinical trial data showed that each agent had antitumor activity in patients previously treated with platinum-based chemotherapy, checkpoint inhibitors, taxanes and those with liver metastases. Enfortumab vedotin was generally well-tolerated, and phase 1 enrollment is ongoing with both agents, with an increased focus on checkpoint-inhibitor treated patients to further understand safety and activity in this population. Detailed findings are summarized below:
- Interim Analysis of a Phase 1 Dose Escalation Trial of ASG-22CE (ASG-22ME; enfortumab vedotin), an Antibody-Drug Conjugate (ADC) in Patients (Pts) with Metastatic Urothelial Cancer (mUC) (Abstract #788P, poster presentation on Sunday, October 9, 2016): Data were reported from 58 patients with metastatic urothelial cancer having a median age of 67 years. Of these patients, 56 patients (97 percent) had undergone treatment with a platinum-based chemotherapy regimen and 20 patients (35 percent) had progressed on or after treatment with checkpoint inhibitors. Thirty-six patients (62 percent) had received two or more prior systemic therapies. The primary endpoints of the ongoing clinical trial are to evaluate pharmacokinetics and safety of enfortumab vedotin as a monotherapy at escalating doses of 0.5 to 1.25 milligrams per kilogram (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:
- Of the 49 patients evaluable for response, 18 patients (37 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 16.6 weeks.
The recommended phase 2 dose is 1.25 mg/kg. In 17 patients treated at the 1.25 mg/kg dose level, 10 patients (59 percent) had a partial response. Disease control was achieved for 14 patients (82 percent), defined as achieving complete response, partial response or stable disease.
In the 16 patients across dose levels who had previously been treated with checkpoint inhibitors, six patients (38 percent) achieved a partial response. At the recommended phase 2 dose, four out of seven patients (57 percent) previously treated with checkpoint inhibitors achieved a partial response.
In the 12 patients whose cancer had metastasized to the liver, which typically has a poor prognosis, five patients (42 percent) achieved an objective response. Of 20 patients previously treated with taxanes, eight (40 percent) achieved an objective response.
The most common treatment related adverse events of any grade occurring in 20 percent or more of patients were pruritis (31 percent), fatigue (30 percent), diarrhea (29 percent), nausea (28 percent), rash (26 percent) and alopecia (21 percent).
Eight of 19 patients (42 percent) experienced a rash at the recommended phase 2 dose and none of these patients required dose modification or discontinued therapy as a result.
Enrollment is ongoing at 1.25 mg/kg and the study has been amended to include a checkpoint inhibitor-treated cohort to further understand safety and activity in this population.
Is
general: Yes
