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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03260322
Recruitment Status : Recruiting
First Posted : August 24, 2017
Last Update Posted : February 20, 2020
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE August 22, 2017
First Posted Date  ICMJE August 24, 2017
Last Update Posted Date February 20, 2020
Actual Study Start Date  ICMJE September 8, 2017
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2018)
  • Safety and tolerability assessed by Dose Limiting Toxicity (DLT) [ Time Frame: Up to 21 days ]
    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
  • Safety and tolerability assessed by adverse events (AEs) [ Time Frame: Up to 30 days following the last dose of study drug or until initiation of a new anti-cancer treatment, whichever comes first of each treatment period (Up to a maximum of 52 weeks) ]
    Initial and re-treatment. An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product
  • Safety and tolerability assessed by immune-related AEs (irAEs) [ Time Frame: Up to 30 days following the last dose of study drug or until initiation of a new anti-cancer treatment, whichever comes first of each treatment period (Up to a maximum of 52 weeks) ]
    Initial and re-treatment. Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies
  • Safety and tolerability assessed by serious adverse events (SAEs) [ Time Frame: Up to 90 days following the last dose of study drug or until initiation of a new anti-cancer treatment, whichever comes first of each treatment period (Up to a maximum of 60 weeks) ]
    Initial and re-treatment. Adverse event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event
  • Number of participants with laboratory value abnormalities and/or adverse events related to treatment [ Time Frame: Up to 30 days from last dose in safety follow up period for each treatment period (Up to a maximum of 52 weeks) ]
    Initial and re-treatment. Number of participants with potentially clinically significant laboratory values. The laboratory tests include hematology, chemistry, urine dipstick, pregnancy test, thyroid stimulating hormone (TSH) and free T4; Hepatitis B and C; Testosterone and prostate-specific antigen (PSA) (metastatic castration resistant prostate cancer (mCRPC) only)
  • Safety and tolerability assessed by 12-lead electrocardiogram (ECG) [ Time Frame: Up to end of treatment (up to 48 weeks for each treatment period) ]
    Initial and re-treatment. ECGs should be obtained after the participant has rested quietly and is awake in a fully supine position (or semi-recumbent, if supine is not tolerated) for 10 minutes before the first ECG from a triplicate or single ECG. Any clinically significant adverse changes on the ECG will be reported as (serious) Adverse Event
  • Number of participants with vital signs abnormalities and/or adverse events related to treatment [ Time Frame: Up to 90 days from last dose in safety follow up period for each treatment period (Up to a maximum of 60 weeks) ]
    Initial and re-treatment. Number of participants with potentially clinically significant vital sign values. Vital signs will include systolic and diastolic blood pressure, radial pulse and temperature. All vital signs will be measured with the subject in the sitting or supine position
  • Number of participants with Physical Exam abnormalities and/or adverse events related to treatment [ Time Frame: Up to end of treatment (up to 48 weeks for each treatment period) ]
    Initial and re-treatment. Standard, full physical examinations will be performed at screening to assess general appearance, skin, eyes, ears, nose, throat, neck, cardiovascular system, chest and lungs, abdomen, musculoskeletal system, neurologic status, mental status, and lymphatic system
  • Safety and tolerability assessed by ECOG performance status [ Time Frame: Up to 30 days from last dose in safety follow up period of each treatment period (Up to a maximum of 52 weeks) ]
    Initial and re-treatment. The eastern cooperative oncology group (ECOG) Scale [Oken, 1982] will be used to assess performance status.0 = Fully active, able to carry on all predisease performance without restriction; 1=Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature; 2= Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3= Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4= Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
  • Pharmacokinetics (PK) of ASP8374 in serum: AUClast (Initial treatment, escalation cohorts in monotherapy only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (for cycle 1 only) ]
    AUClast: area under the concentration-time curve from the time of dosing to the last measurable concentration. AUClast will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of ASP8374 in serum: AUCinf (Initial treatment, escalation cohorts in monotherapy only) [ Time Frame: Cycle 1: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (for cycle 1 only) ]
    AUCinf: area under the concentration-time curve from the time of dosing extrapolated to time infinity. AUCinf will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of ASP8374 in serum: AUCtau (Initial treatment, escalation cohorts in monotherapy only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (for cycle 1 only) ]
    AUCtau: Area under the concentration-time curve from the time of dosing to the start of the next dosing interval. AUCtau will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of ASP8374 in serum: Cmax (Initial treatment, escalation cohorts in monotherapy only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only) ]
    Cmax: maximum concentration. Cmax will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of ASP8374 in serum: Ctrough (Initial treatment, escalation and expansion cohorts in both monotherapy and combination therapy) [ Time Frame: Cycle 2, 4, 7, 10 and 15: day 1: predose 0 hr ]
    Ctrough: Trough concentration. Ctrough will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of pembrolizumab in serum: Ctrough (Initial treatment, escalation cohorts in combination therapy) [ Time Frame: Cycle 2, 4, 7, 10 and 15: day 1: predose 0 hr ]
    Ctrough: Trough concentration. Ctrough will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of ASP8374 in serum: Ctrough (Re-treatment, escalation and expansion cohorts in both monotherapy and combination therapy) [ Time Frame: Cycle 5, 10 and 15: day 1: predose 0 hr ]
    Ctrough: Trough concentration. Ctrough will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of ASP8374 in serum: tmax (Initial treatment, escalation cohorts in monotherapy only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only) ]
    tmax: time of maximum concentration. tmax will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of ASP8374 in serum: t1/2 (Initial treatment, escalation cohorts in monotherapy only) [ Time Frame: Cycle 1: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose ]
    t1/2: terminal elimination half-life. t1/2 will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of ASP8374 in serum: CL (Initial treatment, escalation cohorts in monotherapy only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only) ]
    CL: Clearance. CL will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of ASP8374 in serum: Vz (Initial treatment, escalation cohorts in monotherapy only) [ Time Frame: Cycle 1: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose ]
    Vz: Volume of distribution after intravenous dosing during the terminal elimination phase. Vz will be derived from the PK serum samples collected.
  • Pharmacokinetics (PK) of ASP8374 in serum: Vss (Initial treatment, escalation cohorts in monotherapy only) [ Time Frame: Cycle 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose ]
    Vss: Volume of distribution at steady state after intravenous dosing. Vss will be derived from the PK serum samples collected.
Original Primary Outcome Measures  ICMJE
 (submitted: August 22, 2017)
  • Safety and tolerability assessed by Dose Limiting Toxicity (DLT) [ Time Frame: Up to 21 days ]
    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
  • Safety and tolerability assessed by adverse events (AEs) [ Time Frame: Up to 30 days following the last dose of study drug or until initiation of a new anti-cancer treatment, whichever comes first of each treatment period (Up to a maximum of 48 weeks + 30 days follow up period) ]
    Initial and re-treatment. An AE is any untoward medical occurrence in a subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product
  • Safety and tolerability assessed by immune-related AEs (irAEs) [ Time Frame: Up to 30 days following the last dose of study drug or until initiation of a new anti-cancer treatment, whichever comes first of each treatment period (Up to a maximum of 48 weeks + 30 days follow up period) ]
    Initial and re-treatment. Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies
  • Safety and tolerability assessed by serious adverse events (SAEs) [ Time Frame: Up to 90 days following the last dose of study drug or until initiation of a new anti-cancer treatment, whichever comes first of each treatment period (Up to a maximum of 48 weeks + 90 days follow up period) ]
    Initial and re-treatment. Adverse event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event
  • Number of participants with laboratory value abnormalities and/or adverse events related to treatment [ Time Frame: Up to 30 days from last dose in safety follow up period for each treatment period (Up to a maximum of 48 weeks + 30 days follow up period) ]
    Initial and re-treatment. Number of participants with potentially clinically significant laboratory values. The laboratory tests include hematology, chemistry, urine dipstick, pregnancy test, thyroid stimulating hormone (TSH) and free T4; Hepatitis B and C; Testosterone and prostate-specific antigen (PSA) (metastatic castration resistant prostate cancer (mCRPC) only)
  • Safety and tolerability assessed by 12-lead electrocardiogram (ECG) [ Time Frame: Up to end of treatment (up to 48 weeks for each treatment period) ]
    Initial and re-treatment. ECGs should be obtained after the participant has rested quietly and is awake in a fully supine position (or semi-recumbent, if supine is not tolerated) for 10 minutes before the first ECG from a triplicate or single ECG. Any clinically significant adverse changes on the ECG will be reported as (serious) Adverse Event
  • Number of participants with vital signs abnormalities and/or adverse events related to treatment [ Time Frame: Up to 90 days from last dose in safety follow up period for each treatment period (Up to a maximum of 48 weeks + 90 days follow up period) ]
    Initial and re-treatment. Number of participants with potentially clinically significant vital sign values. Vital signs will include systolic and diastolic blood pressure, radial pulse and temperature. All vital signs will be measured with the subject in the sitting or supine position
  • Number of participants with Physical Exam abnormalities and/or adverse events related to treatment [ Time Frame: Up to end of treatment (up to 48 weeks for each treatment period) ]
    Initial and re-treatment. Standard, full physical examinations will be performed at screening to assess general appearance, skin, eyes, ears, nose, throat, neck, cardiovascular system, chest and lungs, abdomen, musculoskeletal system, neurologic status, mental status, and lymphatic system
  • Safety and tolerability assessed by ECOG performance status [ Time Frame: Up to 30 days from last dose in safety follow up period of each treatment period (Up to a maximum of 48 weeks + 30 days follow up period) ]
    Initial and re-treatment. The eastern cooperative oncology group (ECOG) Scale [Oken, 1982] will be used to assess performance status.0 = Fully active, able to carry on all predisease performance without restriction; 1=Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature; 2= Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3= Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4= Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
  • Pharmacokinetics (PK) of ASP8374 in serum: AUClast (Initial treatment, escalation cohorts only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (for cycle 1 only) ]
    AUClast: area under the concentration-time curve from the time of dosing to the last measurable concentration. AUClast will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: AUCinf (Initial treatment, escalation cohorts only) [ Time Frame: Cycle 1: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (for cycle 1 only) ]
    AUCinf: area under the concentration-time curve from the time of dosing extrapolated to time infinity. AUCinf will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: AUCtau (Initial treatment, escalation cohorts only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (for cycle 1 only) ]
    AUCtau: Area under the concentration-time curve from the time of dosing to the start of the next dosing interval. AUCtau will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: Cmax (Initial treatment, escalation cohorts only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only). Cycle 2 and 4: day 1: end of dosing ]
    Cmax: maximum concentration. Cmax will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: Cmax (Initial treatment, expansion cohorts only) [ Time Frame: Cycle 1, 2, 4 and 7: day 1: end of dosing ]
    Cmax: maximum concentration. Cmax will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: Cmax (Re-treatment, escalation and expansion cohorts) [ Time Frame: Cycle 1 and 5: day 1: end of dosing ]
    Cmax: maximum concentration. Cmax will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: Ctrough (Initial treatment, escalation and expansion cohorts) [ Time Frame: Cycle 2, 4 and 7: day 1: predose 0 hr. Every 5 cycles greater than or equal to 10: Day 1, predose 0 hr ]
    Ctrough: Trough concentration. Ctrough will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: Ctrough (Re-treatment, escalation and expansion cohorts) [ Time Frame: Cycle 5: Day 1: predose 0 hr. Every 5 cycles greater than or equal to 10: Day 1: predose 0 hr ]
    Ctrough: Trough concentration. Ctrough will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: Tmax (Initial treatment, escalation cohorts only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only) ]
    Tmax: time of maximum concentration. Tmax will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: T1/2 (Initial treatment, escalation cohorts only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only) ]
    T1/2: terminal elimination half-life. T1/2 will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: CL (Initial treatment, escalation cohorts only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only) ]
    CL: Clearance. CL will be derived from the PK serum samples collected
  • Pharmacokinetics (PK) of ASP8374 in serum: V (Initial treatment, escalation cohorts only) [ Time Frame: Cycle 1 and 7: day 1: predose 0 hr, end of dosing, 4 hr postdose; day 2: 24 hr postdose; day 3: 48 hr postdose; day 8: 168 hr postdose; day 15: 336 hr postdose; day 22: 504 hr postdose (cycle 1 only) ]
    V: Volume of distribution. V will be derived from the PK serum samples collected
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2017)
  • 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 ]
    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
  • 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 ]
    Initial and re-treatment. DOR will be calculated only for the subgroup of participants with confirmed response CR/PR
  • Persistance of response after discontinuation by iRECIST [ Time Frame: Up to end of follow up period (up to 93 weeks) of each treatment period ]
    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
  • 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 ]
    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)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
Brief 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Drug: ASP8374
    intravenous
  • Drug: Pembrolizumab
    intravenous
    Other Name: Keytruda
Study Arms  ICMJE
  • Experimental: ASP8374
    Participants 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).
    Intervention: Drug: ASP8374
  • Experimental: ASP8374 and pembrolizumab
    Participants 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).
    Interventions:
    • Drug: ASP8374
    • Drug: Pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 28, 2018)
363
Original Estimated Enrollment  ICMJE
 (submitted: August 22, 2017)
200
Estimated Study Completion Date  ICMJE April 2022
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Astellas Pharma Global Development, Inc. 800-888-7704 Astellas.registration@astellas.com
Listed Location Countries  ICMJE United States,   Canada,   Italy,   Japan,   Korea, Republic of,   Portugal,   Spain,   Taiwan,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03260322
Other Study ID Numbers  ICMJE 8374-CL-0101
2018-001146-34 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Study Sponsor  ICMJE Astellas Pharma Global Development, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Vice President Medical Sciences - Oncology Astellas Pharma Global Development, Inc.
PRS Account Astellas Pharma Inc
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP