A Study of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumours That Express Nectin-4

Official Title

A Phase 1 Study of the Safety and Pharmacokinetics of Escalating Doses of ASG-22CE Given as Monotherapy in Subjects With Metastatic Urothelial Cancer and Other Malignant Solid Tumours That Express Nectin-4

Summary:

The purpose of this study is to evaluate the safety and pharmacokinetics ASG-22CE as well as assess the immunogenicity and antitumour activity in subjects with metastatic urothelial cancer and other malignant solid tumours.

Trial Description

Primary Outcome:

  • Incidence of adverse events
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI)
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax)
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Trough concentration (Ctrough)
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax)
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7)
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2)
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL)
  • Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss)
Secondary Outcome:
  • Incidence of Anti-Drug Antibody (ADA)
  • Tumour response
  • Objective response rate
  • Disease control rate
  • Progression Free Survival (PFS)
  • Overall Survival
  • Duration of Response
All subjects will receive a single 30 minute IV infusion of ASG-22CE once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 4 weeks. This is a 3 part study. Part A will evaluate ASG-22CE in subjects with histologically confirmed malignant solid tumours (excluding sarcomas) that are resistant or have recurred. Subjects will continue treatment until disease progression, intolerability of ASG-22CE, investigator decision or consent withdrawal. Part A will follow a modified Continual Reassessment Method (mCRM). Part B, will evaluate ASG-22CE in 3 different expansion cohorts: 1) Urothelial cancer subjects who have not received any prior lines of therapy and who are unfit for Cisplatin-based chemotherapy (Cisineligible) defined as a Creatinine Clearance ≥ 15 ml/min and < 60 ml/min, 2) subjects with Metastatic Non Small Cell Lung Cancer (NSCLC) and 3) subjects with Metastatic Ovarian Cancer. Enrollment into Part B will occur after the maximum tolerated dose (MTD) has been assessed in Part A, and the preliminary recommended phase 2 dose (RP2D) has been established. Subjects will continue treatment until disease progression, intolerability of ASG-22CE or consent withdrawal. Part C will evaluate ASG-22CE at the preliminary RP2D (determined from Part A) in subjects who have been previously treated with immune checkpoint inhibitors (CPI) in the metastatic setting. Subjects will continue treatment until disease progression, intolerability of ASG-22CE, investigator decision or consent withdrawal. All subjects will be followed post-treatment every 2 months via disease assessment or telephone contact to obtain information on disease progression and death. For Part A (Dose Escalation) and Part B (Cis-ineligible), a data review team (DRT) will review cumulative unaudited data on an interim basis to explore additional doses and/or schedules, or the expansion of existing cohorts. Doses intermediate to those predefined in the protocol may be explored with DRT endorsement.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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