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

Titre officiel

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

Sommaire:

Le but de cette étude est d'évaluer l'innocuité et la pharmacocinétique de l'ASG-22CE, ainsi que  l'immunogénicité et l'activité antitumorale chez les sujets atteints du cancer urothélial métastatique.

Description de l'essai

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 enfortumab vedotin once weekly for the first 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 enfortumab vedotin 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 enfortumab vedotin, investigator decision or consent withdrawal. Part A will follow a modified Continual Reassessment Method (mCRM). Part B, will evaluate enfortumab vedotin in 3 different expansion cohorts: 1) Urothelial cancer subjects with renal insufficiency defined as a Creatinine Clearance ≥ 15 ml/min and < 30 ml/min, 2) subjects with Metastatic Non Small Cell Lung Cancer (NSCLC) and 3) subjects with Metastatic Ovarian Cancer. With the exception of the renal insufficiency cohort, enrollment into Part B will occur at the recommended phase 2 dose (RP2D) established in Part A. Enrollment into the renal insufficiency cohort will begin at starting dose and escalated using a 3 + 3 dose escalation design. Subjects will continue treatment until disease progression, intolerability of enfortumab vedotin or consent withdrawal. Part C will evaluate enfortumab vedotin at the 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 enfortumab vedotin, 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.

Voir cet essai sur ClinicalTrials.gov

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