Clinical Trials /

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

NCT03260322

Description:

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 tumor 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-tumor 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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 8374-CL-0101
  • SECONDARY ID: 2018-001146-34
  • NCT ID: NCT03260322

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
ASP8374ASP8374 and pembrolizumab
PembrolizumabKeytrudaASP8374 and pembrolizumab

Purpose

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 tumor 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-tumor 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.

Detailed Description

      This is a multi-center, multiple-dose, dose-escalation and expansion study of ASP8374 as a
      single agent and in combination with pembrolizumab. After discontinuation of study drug
      treatment, all participants will complete an end of treatment visit and safety follow-up
      visits. Participants will be enrolled in respectively escalation cohorts or expansion
      cohorts.

      Escalation cohorts: Approximately 63 participants may be enrolled in the escalation cohorts
      (approximately 33 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 antitumor activity. It is estimated that approximately 300
      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 antitumor activity,
      approximately 363 participants are expected to be enrolled.
    

Trial Arms

NameTypeDescriptionInterventions
ASP8374ExperimentalParticipants will be enrolled in the escalation cohorts or expansion cohorts and receive ASP8374 (monotherapy) intravenously on Day 1 of every 3-week cycle (up to a maximum of 8 dose strengths).
  • ASP8374
ASP8374 and pembrolizumabExperimentalParticipants will be enrolled in the escalation cohorts or expansion cohorts and receive ASP8374 and pembrolizumab (combination therapy) intravenously on Day 1 of every 3-week cycle (up to a maximum of 5 dose strengths of ASP8374 and one fixed dose strength of pembrolizumab).
  • ASP8374
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no
             limit to the number of prior treatment regimens) that is confirmed by available
             pathology records or current biopsy as well as:

               -  Subject in the escalation cohort has received all standard therapies (unless the
                  therapy is contraindicated or intolerable) felt to provide clinical benefit for
                  the subject's specific tumor type. OR

               -  Subject in an expansion cohort has received at least one standard therapy for the
                  subject's specific tumor type.

          -  For Korea, Italy and Portugal only: Subject has locally-advanced (unresectable) or
             metastatic solid tumor malignancy (no limit to the number of prior treatment regimens)
             that is confirmed by available pathology records or current biopsy and has received
             all standard therapies (unless the therapy is contraindicated or intolerable) felt to
             provide clinical benefit for the subject's specific tumor type.

          -  Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or
             2.

          -  Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was
             at least 21 days prior to initiation of study drug administration. A subject with
             epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)
             mutation-positive NSCLC is allowed to remain on EGFR tyrosine kinase inhibitor (TKI)
             therapy or ALK inhibitor until 4 days prior to the start of study drug administration.

          -  For Korea only: Subject's last dose of prior antineoplastic therapy, including any
             immunotherapy, was at least 21 days prior to initiation of study drug administration.
             For drugs with a half-life greater than or equal to 21 days, the investigator should
             consider if this washout is sufficient. A subject with epidermal growth factor
             receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is allowed to
             remain on EGFR tyrosine kinase inhibitor (TKI) therapy until 7 days prior to the start
             of study drug administration.

          -  Subject has completed any radiotherapy (including stereotactic radiosurgery) at least
             2 weeks prior to study drug administration.

          -  Subject's adverse events (excluding alopecia) from prior therapy have improved to
             grade 1 or baseline within 14 days prior to start of study treatment.

          -  Subject with metastatic castration resistant prostate cancer (mCRPC) (positive bone
             scan and/or soft tissue disease documented by computed tomography (CT) / magnetic
             resonance imaging (MRI)) meets both of the following:

               -  Subject has serum testosterone ≤ 50 ng/dL at screening.

               -  Subject has had an orchiectomy or plans to continue androgen deprivation therapy
                  (ADT) for the duration of study treatment.

          -  Subject has adequate organ function prior to start of study treatment as indicated by
             the following laboratory values. If a subject has received a recent blood transfusion,
             the laboratory tests must be obtained ≥ 4 weeks after any blood transfusion.

          -  Female subject is eligible to participate if she is not pregnant and at least 1 of the
             following conditions applies:

               -  Not a woman of childbearing potential (WOCBP)

               -  WOCBP who agrees to follow the contraceptive guidance throughout the treatment
                  period and for at least 6 months after the final study drug administration.

          -  Female subject must agree not to breastfeed starting at screening and throughout the
             study treatment, and for 6 months after the final study drug administration.

          -  Female subject must not donate ova starting at screening and throughout the study
             treatment, and for 6 months after the final study drug administration.

          -  A male subject with female partner(s) of childbearing potential must agree to use
             contraception as detailed during the treatment period and for at least 6 months after
             the final study drug administration.

          -  Male subject must not donate sperm starting at screening and throughout the study
             treatment, and for 6 months after the final study drug administration.

          -  Male subject with a pregnant or breastfeeding partner(s) must agree to remain
             abstinent or use a condom for the duration of the pregnancy or time partner is
             breastfeeding throughout the study treatment and for 6 months after the final study
             drug administration.

          -  Subject agrees not to participate in another interventional study while receiving
             study drug (subjects who are currently in the follow-up period of an interventional
             clinical trial are allowed).

        Additional Inclusion Criteria for Subjects in the Expansion Cohorts:

          -  Subject meets one of the following:

               -  Subject has the tumor type for which a confirmed response was observed in a
                  monotherapy or combination therapy dose escalation cohort; or

               -  For an expansion cohort opened due to achieving predicted efficacious exposure,
                  subject has squamous cell carcinoma of the head and neck (SCCHN); or

               -  For tumor specific expansion cohorts of ASP8374 with pembrolizumab, subject has
                  the applicable tumor type (e.g., non-small cell lung cancer (NSCLC), bladder
                  cancer, gastric cancer, metastatic castration resistant prostate cancer (MCRPC)
                  or colorectal cancer (CRC)).

          -  Subject has at least 1 measureable lesion per Response Evaluation Criteria in Solid
             Tumors (RECIST) 1.1. The measureable lesion must be outside the field of radiation if
             subject had prior radiotherapy. Subjects with mCRPC who do not have measurable lesions
             must have at least one of the following:

               -  Progression with 2 or more new bone lesions; or

               -  Prostate-specific antigen (PSA) progression (defined as a minimum of three rising
                  PSA levels with an interval of ≥ 1 week between each determination) within 6
                  weeks prior to study drug administration and a PSA value at the screening visit ≥
                  2 ng/mL.

          -  Subject consents to provide an available tumor specimen in a tissue block or unstained
             serial slides obtained within 56 days prior to first dose of study treatment, or
             subject is an appropriate candidate for tumor biopsy and is amenable to undergoing a
             tumor biopsy (core needle biopsy or excision) during the screening period.This does
             not apply to subjects with mCRPC without measurable disease.

          -  Subject in any expansion cohort, is an appropriate candidate for tumor biopsy and
             consents to undergoing a tumor biopsy (core needle biopsy or excision) during the
             treatment period as indicated in the Schedule of Assessments.

        Exclusion:

          -  Subject weighs < 45 kg at screening.

          -  Subject has received investigational therapy (other than an investigational epidermal
             growth factor receptor tyrosine kinase inhibitor (EGFR TKI) in a subject with EGFR
             activating mutations or ALK inhibitor in a subject with an ALK mutation) within 21
             days prior to start of study drug.

          -  Subject requires or has received systemic steroid therapy or any other
             immunosuppressive therapy within 14 days prior to study drug administration. Subjects
             using a physiologic replacement dose of hydrocortisone or its equivalent (defined as
             up to 30 mg per day of hydrocortisone up to 10 mg per day of prednisone) are allowed.

          -  Subject has symptomatic central nervous system (CNS) metastases or subject has
             evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans).
             Subjects with previously treated CNS metastases are eligible, if subject is clinically
             stable and have no evidence of CNS progression by imaging for at least 4 weeks prior
             to start of study treatment and are not requiring immunosuppressive doses of systemic
             steroids (> 30 mg per day of hydrocortisone or > 10 mg per day of prednisone or
             equivalent) for longer than 2 weeks.

          -  Subject has an active autoimmune disease. Subjects with type 1 diabetes mellitus,
             endocrinopathies stably maintained on appropriate replacement therapy, or skin
             disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment
             are allowed.

          -  Subject was discontinued from prior immunomodulatory therapy due to a grade ≥ 3
             toxicity that was mechanistically related (e.g., immune related) to the agent.

          -  Subject has known history of serious hypersensitivity reaction to a known ingredient
             of ASP8374 or pembrolizumab or severe hypersensitivity reaction to treatment with
             another monoclonal antibody.

          -  Subject has a known history of Human Immunodeficiency Virus.

          -  Subject with positive for Hepatitis B virus (HBV) antibodies and surface antigen
             (including acute HBV or chronic HBV) or Hepatitis C ([HCV]; ribonucleic acid [RNA]
             detected by qualitative assay). Hepatitis C RNA testing is not required in subjects
             with negative Hepatitis C antibody testing.

          -  Subject has received a live vaccine against infectious diseases within 28 days prior
             to initiation of study treatment.

          -  Subject has a history of drug-induced pneumonitis (interstitial lung disease) or
             currently has pneumonitis.

          -  Subject has an infection requiring systemic therapy within 14 days prior to study drug
             treatment.

          -  Subject has received a prior allogeneic bone marrow or solid organ transplant.

          -  Subject is expected to require another form of antineoplastic therapy while on study
             treatment.

          -  Subject has had a myocardial infarction or unstable angina within 6 months prior to
             the start of study treatment or currently has an uncontrolled illness including, but
             not limited to symptomatic congestive heart failure, clinically significant cardiac
             disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
             situations that would limit compliance with study requirements.

          -  Any condition that makes the subject unsuitable for study participation.

          -  Subject has had a major surgical procedure and has not completely recovered within 28
             days prior to the start of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability assessed by Dose Limiting Toxicity (DLT)
Time Frame:Up to 21 days
Safety Issue:
Description:DLT as graded using National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] Version 4.03. The DLT observation period may be increased if deemed appropriate by the Dose Escalation and Safety Committee

Secondary Outcome Measures

Measure:Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST
Time Frame:Up to end of follow up period (up to 93 weeks) of each treatment period
Safety Issue:
Description:Initial and re-treatment. 'Immune' Response Evaluation Criteria in Solid Tumors (iRECIST). ORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR or PR
Measure:Duration of response (DOR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST
Time Frame:Up to end of follow up period (up to 93 weeks) of each treatment period
Safety Issue:
Description:Initial and re-treatment. DOR will be calculated only for the subgroup of participants with confirmed response CR/PR
Measure:Persistance of response after discontinuation by iRECIST
Time Frame:Up to end of follow up period (up to 93 weeks) of each treatment period
Safety Issue:
Description:Initial and re-treatment. Persistence of response after discontinuation is defined for participants who discontinued the treatment and responded to the treatment per iRECIST only
Measure:Disease control rate (DCR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and iRECIST
Time Frame:Up to End of follow up period (up to 93 weeks) of each treatment period
Safety Issue:
Description:Initial and re-treatment. DCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR, PR or Stable Disease (SD)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial Keywords

  • Pembrolizumab
  • Oncology
  • Tumors
  • ASP8374
  • Locally advanced or metastatic solid tumor malignancies

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