A Multiple-dose Study of ASP8374, an Immune Checkpoint Inhibitor, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumours

Official Title

A Phase 1b Study of ASP8374, an Immune Checkpoint Inhibitor, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumours

Summary:

The primary purpose of this study is to evaluate the tolerability and safety profile of ASP8374 when administered as a single agent and in combination with pembrolizumab in participants with locally advanced (unresectable) or metastatic solid tumour malignancies. Also primary purpose is to characterize the pharmacokinetic profile of ASP8374 when administered as a single agent and in combination with pembrolizumab. Last primary purpose of this study is to determine the recommended Phase 2 dose (RP2D) of ASP8374 when administered as a single agent and in combination with pembrolizumab. The secondary purpose of this study is to evaluate the anti-tumour effect (objective response rate [ORR], duration of response [DOR], persistence of response after discontinuation, and disease control rate [DCR]) of ASP8374 when administered as a single agent and in combination with pembrolizumab.

Trial Description

Primary Outcome:

  • Safety and tolerability assessed by Dose Limiting Toxicity (DLT)
  • Safety and tolerability assessed by adverse events (AEs)
  • Safety and tolerability assessed by immune-related AEs (irAEs)
  • Safety and tolerability assessed by serious adverse events (SAEs)
  • Number of participants with laboratory value abnormalities and/or adverse events related to treatment
  • Safety and tolerability assessed by 12-lead electrocardiogram (ECG)
  • Number of participants with vital signs abnormalities and/or adverse events related to treatment
  • Number of participants with Physical Exam abnormalities and/or adverse events related to treatment
  • Safety and tolerability assessed by ECOG performance status
  • Pharmacokinetics (PK) of ASP8374 in serum: AUClast (Initial treatment, escalation cohorts in monotherapy only)
  • Pharmacokinetics (PK) of ASP8374 in serum: AUCinf (Initial treatment, escalation cohorts in monotherapy only)
  • Pharmacokinetics (PK) of ASP8374 in serum: AUCtau (Initial treatment, escalation cohorts in monotherapy only)
  • Pharmacokinetics (PK) of ASP8374 in serum: Cmax (Initial treatment, escalation cohorts in monotherapy only)
  • Pharmacokinetics (PK) of ASP8374 in serum: Ctrough (Initial treatment, escalation and expansion cohorts in both monotherapy and combination therapy)
  • Pharmacokinetics (PK) of pembrolizumab in serum: Ctrough (Initial treatment, escalation cohorts in combination therapy)
  • Pharmacokinetics (PK) of ASP8374 in serum: Ctrough (Re-treatment, escalation and expansion cohorts in both monotherapy and combination therapy)
  • Pharmacokinetics (PK) of ASP8374 in serum: tmax (Initial treatment, escalation cohorts in monotherapy only)
  • Pharmacokinetics (PK) of ASP8374 in serum: t1/2 (Initial treatment, escalation cohorts in monotherapy only)
  • Pharmacokinetics (PK) of ASP8374 in serum: CL (Initial treatment, escalation cohorts in monotherapy only)
  • Pharmacokinetics (PK) of ASP8374 in serum: Vz (Initial treatment, escalation cohorts in monotherapy only)
  • Pharmacokinetics (PK) of ASP8374 in serum: Vss (Initial treatment, escalation cohorts in monotherapy only)
Secondary Outcome:
  • Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and iRECIST
  • Duration of response (DOR) by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and iRECIST
  • Persistence of response after discontinuation by iRECIST
  • Disease control rate (DCR) by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and iRECIST
Screening and enrollment are temporarily on hold due to COVID-19. This is a multi-centre, multiple-dose, dose-escalation and expansion study of ASP8374 as a single agent and in combination with pembrolizumab. After discontinuation of study drug treatment (initial treatment and re-treatment), all participants will complete an end of treatment visit along with 30-day and 90-day safety follow-up visits from the last dose of ASP8374. Participants will be enrolled in respectively escalation cohorts or expansion cohorts. The 90-day safety follow-up visit is optional for participants who discontinue due to progressive disease or initiate new anticancer treatment after the last dose of study drug. Escalation cohorts: Approximately 60 participants may be enrolled in the escalation cohorts (approximately 30 participants for monotherapy and 30 participants for combination therapy). Expansion cohorts: The total number of subjects in the expansion cohorts will depend on the observed pharmacokinetic and antitumour activity. It is estimated that approximately 240 participants may be enrolled in the monotherapy and combination therapy expansion cohorts. As the number of participants in the escalation cohorts and the expansion cohorts will depend on the observed Dose Limiting Toxicity (DLT), pharmacokinetics and antitumour activity, approximately 300 participants are expected to be enrolled.

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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