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Trial record 1 of 1 for:    NCT03565445
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A Study of ASP1948, Targeting an Immune Modulatory Receptor, in Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03565445
Recruitment Status : Recruiting
First Posted : June 21, 2018
Last Update Posted : June 26, 2020
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE May 25, 2018
First Posted Date  ICMJE June 21, 2018
Last Update Posted Date June 26, 2020
Actual Study Start Date  ICMJE July 2, 2018
Estimated Primary Completion Date July 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 25, 2020)
  • Safety and tolerability assessed by dose limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]
    A DLT is defined as any of the prespecified Adverse Events (AEs) (graded using National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] version 4.03) that the investigator (or sponsor) cannot clearly attribute to a cause other than study drug.
  • Safety and tolerability assessed by Adverse Events (AEs) (Initial Treatment) [ Time Frame: Up to a maximum of 52 weeks ]
    An AE is any untoward medical occurrence in a participant, 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. AEs will be coded using medical dictionary for regulatory activities (MedDRA) and graded using NCI-CTCAE version 4.03.
  • Safety and tolerability assessed by Adverse Events (AEs) (Retreatment) [ Time Frame: Up to a maximum of 52 weeks ]
    An AE is any untoward medical occurrence in a participant, 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. AEs will be coded using medical dictionary for regulatory activities (MedDRA) and graded using NCI-CTCAE version 4.03.
  • Safety and tolerability assessed by immune-related Adverse Events (irAEs) (Initial Treatment) [ Time Frame: Up to a maximum of 52 weeks ]
    Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies.
  • Safety and tolerability assessed by immune-related Adverse Events (irAEs) (Retreatment) [ Time Frame: Up to a maximum of 52 weeks ]
    Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies.
  • Safety and tolerability assessed by infusion-related reaction (IRRs) (Initial Treatment) [ Time Frame: Up to a maximum of 52 weeks ]
    IRRs are considered AEs of special interest. In the event a participant is diagnosed with an IRR, then it should be reported as an AE.
  • Safety and tolerability assessed by infusion-related reaction (IRRs) (Retreatment) [ Time Frame: Up to a maximum of 52 weeks ]
    IRRs are considered AEs of special interest. In the event a participant is diagnosed with an IRR, then it should be reported as an AE.
  • Safety and tolerability assessed by Serious Adverse Events (SAEs) (Initial Treatment) [ Time Frame: Up to a maximum of 60 weeks ]
    An AE is considered "serious" if, it results in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE). Hospitalization for treatment/observation/examination caused by AE is to be considered as serious; and other medically important events.
  • Safety and tolerability assessed by Serious Adverse Events (SAEs) (Retreatment) [ Time Frame: Up to a maximum of 60 weeks ]
    An AE is considered "serious" if, it results in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE). Hospitalization for treatment/observation/examination caused by AE is to be considered as serious; and other medically important events.
  • Number of participants with laboratory value abnormalities and/or adverse events (Initial Treatment) [ Time Frame: Up to a maximum of 52 weeks ]
    Number of participants with potentially clinically significant laboratory values.
  • Number of participants with laboratory value abnormalities and/or adverse events (Retreatment) [ Time Frame: Up to a maximum of 52 weeks ]
    Number of participants with potentially clinically significant laboratory values.
  • Safety assessed by 12- lead electrocardiogram (ECG) (Initial Treatment) [ Time Frame: Up to a maximum of 48 weeks ]
    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. For ECGs done in triplicate, there should be at least 2 minutes between each ECG. Any abnormal ECGs including those that worsen from baseline, that is considered to be clinically significant and not related to underlying disease, is to be reported as an (S)AE.
  • Safety assessed by 12- lead electrocardiogram (ECG) (Retreatment) [ Time Frame: Up to a maximum of 48 weeks ]
    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. For ECGs done in triplicate, there should be at least 2 minutes between each ECG. Any abnormal ECGs including those that worsen from baseline, that is considered to be clinically significant and not related to underlying disease, is to be reported as an (S)AE.
  • Number of participants with vital signs abnormalities and/or adverse events (Initial Treatment) [ Time Frame: Up to a maximum of 60 weeks ]
    Number of participants with potentially clinically significant vital sign values.
  • Number of participants with vital signs abnormalities and/or adverse events (Retreatment) [ Time Frame: Up to a maximum of 60 weeks ]
    Number of participants with potentially clinically significant vital sign values.
  • Number of participants with Physical Exam abnormalities and/or adverse events (Initial Treatment) [ Time Frame: Up to a maximum of 48 weeks ]
    Number of participants with potentially clinically significant physical exam values.
  • Number of participants with Physical Exam abnormalities and/or adverse events (Retreatment) [ Time Frame: Up to a maximum of 48 weeks ]
    Number of participants with potentially clinically significant physical exam values.
  • Safety assessed by Eastern Cooperative Oncology Group Performance Status (ECOG PS) (Initial Treatment) [ Time Frame: Up to a maximum of 52 weeks ]
    The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 4 (completely disabled). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
  • Safety assessed by Eastern Cooperative Oncology Group Performance Status (ECOG PS) (Retreatment) [ Time Frame: Up to a maximum of 52 weeks ]
    The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 4 (completely disabled). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
  • Pharmacokinetics (PK) of ASP1948 in serum: AUClast [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Area under the concentration time curve from the time of dosing to the last measurable concentration (AUClast) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: AUCinf [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: AUCinf %extrap [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf %extrap) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: AUCtau [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Area under the concentration-time curve from the time of dosing to the start of next dosing interval (AUCtau) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: Cmax [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Maximum concentration (Cmax) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: Ctrough [ Time Frame: Up to a maximum of 48 weeks for each treatment period ]
    Initial and retreatment. Concentration immediately prior to dosing at multiple dosing (Ctrough) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: tmax [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Time of the maximum concentration (tmax) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: t1/2 [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Terminal elimination half-life (t1/2) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: tlast [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Time of last measurable concentration (tlast) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: CL [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Total clearance after intravenous dosing (CL) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: V [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Volume of distribution after intravenous dosing (V) will be derived from the pharmacokinetic (PK) serum samples collected.
Original Primary Outcome Measures  ICMJE
 (submitted: June 20, 2018)
  • Safety and tolerability assessed by dose limiting toxicities (DLTs) [ Time Frame: Up to 28 days ]
    A DLT is defined as any of the prespecified Adverse Events (AEs) (graded using National Cancer Institute Common Toxicity Criteria for Adverse Events [NCI-CTCAE] version 4.03) that the investigator (or sponsor) cannot clearly attribute to a cause other than study drug.
  • Safety and tolerability assessed by Adverse Events (AEs) [ Time Frame: Up to a maximum of 52 weeks ]
    Initial and retreatment. An AE is any untoward medical occurrence in a participant, 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. AEs will be coded using medical dictionary for regulatory activities (MedDRA) and graded using NCI-CTCAE version 4.03.
  • Safety and tolerability assessed by immune-related Adverse Events (irAEs) [ Time Frame: Up to a maximum of 52 weeks ]
    Initial and retreatment. Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies.
  • Safety and tolerability assessed by infusion-related reaction (IRRs) [ Time Frame: Up to a maximum of 52 weeks ]
    Initial and retreatment. IRRs are considered AEs of special interest. In the event a participant is diagnosed with an IRR, then it should be reported as an AE.
  • Safety and tolerability assessed by Serious Adverse Events (SAEs) [ Time Frame: Up to a maximum of 60 weeks ]
    Initial and retreatment. An AE is considered "serious" if, it results in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly or birth defect; requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization (except if prolongation of planned hospitalization is not caused by an AE). Hospitalization for treatment/observation/examination caused by AE is to be considered as serious; and other medically important events.
  • Number of participants with laboratory value abnormalities and/or adverse events [ Time Frame: Up to a maximum of 52 weeks ]
    Initial and retreatment. Number of participants with potentially clinically significant laboratory values.
  • Safety assessed by 12- lead electrocardiogram (ECG) [ Time Frame: Up to a maximum of 48 weeks for each treatment period ]
    Initial and retreatment. 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. For ECGs done in triplicate, there should be at least 2 minutes between each ECG. Any abnormal ECGs including those that worsen from baseline, that is considered to be clinically significant and not related to underlying disease, is to be reported as an (S)AE.
  • Number of participants with vital signs abnormalities and/or adverse events [ Time Frame: Up to a maximum of 60 weeks ]
    Initial and retreatment. Number of participants with potentially clinically significant vital sign values.
  • Number of participants with Physical Exam abnormalities and/or adverse events [ Time Frame: Up to a maximum of 48 weeks for each treatment period ]
    Initial and retreatment. Number of participants with potentially clinically significant physical exam values.
  • Safety assessed by Eastern Cooperative Oncology Group Performance Status (ECOG PS) [ Time Frame: Up to a maximum of 52 weeks ]
    Initial and retreatment. The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 4 (completely disabled). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
  • Pharmacokinetics (PK) of ASP1948 in serum: AUClast [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Area under the concentration time curve from the time of dosing to the last measurable concentration (AUClast) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: AUCinf [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: AUCinf %extrap [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf %extrap) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: AUCtau [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Area under the concentration-time curve from the time of dosing to the start of next dosing interval (AUCtau) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: Cmax [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Maximum concentration (Cmax) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: Ctrough [ Time Frame: Up to a maximum of 48 weeks for each treatment period ]
    Initial and retreatment. Concentration immediately prior to dosing at multiple dosing (Ctrough) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: tmax [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Time of the maximum concentration (tmax) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: t1/2 [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Terminal elimination half-life (t1/2) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: tlast [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Time of last measurable concentration (tlast) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: CL [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Total clearance after intravenous dosing (CL) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: Vz [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Volume of distribution after intravenous dosing during the terminal elimination phase (Vz) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1948 in serum: Vss [ Time Frame: Up to a maximum of 22 weeks in initial treatment period of dose escalation ]
    Initial dose escalation treatment only. Volume of distribution at steady state after intravenous dosing (Vss) will be derived from the pharmacokinetic (PK) serum samples collected.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2020)
  • Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 and modified RECIST 1.1 for immune-based therapeutics (iRECIST) (Initial Treatment) [ Time Frame: Up to a maximum of 88 weeks ]
    ORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed complete response (CR) or partial response (PR).
  • Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 and modified RECIST 1.1 for immune-based therapeutics (iRECIST) (Retreatment) [ Time Frame: Up to a maximum of 88 weeks ]
    ORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed complete response (CR) or partial response (PR).
  • Duration of Response (DOR) per RECIST V1.1 and iRECIST (Initial Treatment) [ Time Frame: Up to a maximum of 88 weeks ]
    DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring.
  • Duration of Response (DOR) per RECIST V1.1 and iRECIST (Retreatment) [ Time Frame: Up to a maximum of 88 weeks ]
    DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring.
  • Persistence of response after discontinuation per RECIST V1.1 and iRECIST (Initial Treatment) [ Time Frame: Up to a maximum of 88 weeks ]
    Persistence of response is defined as the time from the date of treatment discontinuation to the date of radiographical progression or date of censoring.
  • Persistence of response after discontinuation per RECIST V1.1 and iRECIST (Retreatment) [ Time Frame: Up to a maximum of 88 weeks ]
    Persistence of response is defined as the time from the date of treatment discontinuation to the date of radiographical progression or date of censoring.
  • Disease Control Rate (DCR) per RECIST V1.1 and iRECIST (Initial Treatment) [ Time Frame: Up to a maximum of 88 weeks ]
    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).
  • Disease Control Rate (DCR) per RECIST V1.1 and iRECIST (Retreatment) [ Time Frame: Up to a maximum of 88 weeks ]
    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
 (submitted: June 20, 2018)
  • Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) V1.1 and modified RECIST 1.1 for immune-based therapeutics (iRECIST) [ Time Frame: Up to a maximum of 93 weeks ]
    Initial and retreatment. ORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed complete response (CR) or partial response (PR).
  • Duration of Response (DOR) per RECIST V1.1 and iRECIST [ Time Frame: Up to a maximum of 93 weeks ]
    Initial and retreatment. DOR is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression/death or date of censoring
  • Persistence of response after discontinuation per RECIST V1.1 and iRECIST [ Time Frame: Up to a maximum of 93 weeks ]
    Initial and retreatment. Persistence of response is defined as the time from the date of treatment discontinuation to the date of radiographical progression or date of censoring.
  • Disease Control Rate (DCR) per RECIST V1.1 and iRECIST [ Time Frame: Up to a maximum of 93 weeks ]
    Initial and retreatment. 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).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ASP1948, Targeting an Immune Modulatory Receptor, in Subjects With Advanced Solid Tumors
Official Title  ICMJE A Phase 1b Study of ASP1948, Targeting an Immune Modulatory Receptor as a Single Agent and in Combination With Nivolumab in Subjects With Advanced Solid Tumors
Brief Summary The purpose of this study is to evaluate the tolerability and safety profile of ASP1948 when administered as a single agent and in combination with nivolumab in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile of ASP1948 when administered as a single agent and in combination with nivolumab and determine the recommended Phase 2 dose (RP2D) of ASP1948 when administered as a single agent and in combination with nivolumab. This study will also evaluate the antitumor effect of ASP1948 when administered as a single agent and in combination with nivolumab.
Detailed Description

This is a dose-escalation and expansion study of ASP1948 as a single agent and in combination with nivolumab. The study consists of 3 periods for monotherapy and combination therapy: screening, treatment and follow up, followed by an optional Re-treatment period for participants that qualify.

The escalation cohorts will evaluate escalating dose levels of ASP1948 in participants with locally advanced (unresectable) or metastatic solid tumor malignancies.

After discontinuation of study drug, 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 study drug.

For dose expansion, the tumor-specific cohorts will include participants with squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), metastatic castration-resistant prostate cancer (mCRPC), ovarian cancer, pancreatic cancer and breast cancer, as well as any tumor types that respond to study drug treatment during dose escalation.

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: ASP1948
    Intravenously (IV)
  • Drug: nivolumab
    Intravenously (IV)
Study Arms  ICMJE
  • Experimental: ASP1948 Dose Escalation
    The monotherapy escalation cohort will evaluate escalating dose levels of ASP1948. Each dose level will enroll approximately 3 or 4 participants. Dose escalation to the next level will be made based on the Bayesian Continual Reassessment Method (CRM).
    Intervention: Drug: ASP1948
  • Experimental: ASP1948 Dose Expansion
    If a confirmed response (iRECIST partial response (iPR) or iRECIST confirmed response (iCR)) per iRECIST occurs in a monotherapy escalation cohort, a tumor specific expansion cohort may be opened in that tumor type, at the dose level in which the confirmed response was observed and at all subsequent dose levels once each dose level has been cleared. Up to 5 expansion cohorts may be opened.
    Intervention: Drug: ASP1948
  • Experimental: ASP1948 Optional Retreatment Period
    Participants may reinitiate study drug treatment after confirmation that they meet all the re-treatment eligibility criteria.
    Intervention: Drug: ASP1948
  • Experimental: ASP1948 plus nivolumab Combination Therapy
    ASP1948 will be administered in combination with a fixed dose of nivolumab every 2 weeks. ASP1948 dose for combination therapy escalation cohorts will start at one dose level below the most recently cleared dose in the monotherapy escalation cohort at the time of opening the combination therapy.
    Interventions:
    • Drug: ASP1948
    • Drug: nivolumab
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: May 23, 2019)
474
Original Estimated Enrollment  ICMJE
 (submitted: June 20, 2018)
254
Estimated Study Completion Date  ICMJE July 2022
Estimated Primary Completion Date July 2022   (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, and has received all standard therapies (unless the therapy is contraindicated or intolerable) felt to provide clinical benefit.
  • 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) or ALK inhibitor therapy until 4 days prior to the start of study drug administration.
  • Subject has completed any radiotherapy (including stereotactic radiosurgery) at least 14 days prior to study drug administration.
  • Subject with metastatic castration-resistant prostate cancer (mCRPC) (positive scan and/or soft tissue disease documented by computed tomography/magnetic resonance imaging) 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 as indicated by laboratory values. (If a subject has received a recent blood transfusion, the laboratory tests must be obtained ≥ 28 days after any blood transfusion.) Note: Growth factors, colony stimulating factors are not permitted in the screening period.
  • Female subject must either:

    • Be of non-childbearing potential: post-menopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or; documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy).
    • Or, if of childbearing potential: Agree not to try to become pregnant during the study treatment and for 6 months after the final study drug administration; and have a negative urine or serum pregnancy test prior to study drug administration; and if heterosexually active, agree to consistently use 1 form of highly effective birth control starting at screening and throughout the study treatment and 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 sexually active male subject with female partner(s) who are of childbearing potential is eligible if :

    • The male subject agrees to use a male condom starting at screening and continues throughout the study treatment, and for 6 months after the final study drug administration.
    • The male subject has not had a vasectomy or is not sterile, as defined below and the subject's female partner(s) is utilizing 1 form of highly effective birth control starting at screening and continuing throughout the study treatment and for 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 has at least 1 measureable lesion per 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 1 of the following:

    • Progression with 2 or more new bone lesions, or
    • Prostate specific antigen (PSA) progression (defined as a minimum of 3 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 available tumor specimen in a tissue block or unstained serial slides obtained within 8 to 56 days prior to first dose of study treatment. Note: This does not apply to subjects with mCRPC who do not have measurable disease.
  • Subject is an appropriate candidate for tumor biopsy and consents to undergoing a tumor biopsy (core needle biopsy or excision) during the treatment period. Note: This does not apply to subjects with mCRPC who do not have measurable disease.
  • Subject meets one of the following:

    • Subject has the tumor type for which a confirmed response was observed in a monotherapy or in combination with nivolumab dose escalation or RP2D 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 RP2D monotherapy or in combination with nivolumab expansion cohorts, subject has NSCLC, mCRPC, ovarian, pancreatic, or breast cancer.

Additional Inclusion Criteria for Re-treatment:

Subjects may be eligible for study drug re-treatment if the study remains open and the subject continues to meet all of the eligibility criteria above (except prior use of this drug) and the following conditions:

  • Subject stopped initial treatment with ASP1948 or ASP1948 in combination with nivolumab after attaining a confirmed CR or PR or SD.
  • Subject experienced a confirmed disease progression by iRECIST (iCPD) (or unconfirmed progressive disease by iRECIST (iUPD) if subject is not clinically stable to await confirmatory scan) after stopping their initial treatment with ASP1948 or ASP1948 in combination with nivolumab.
  • Subject did not receive any prohibited anti-cancer treatment since the last dose of ASP1948 or ASP1948 in combination with nivolumab.
  • Subject did not experience a toxicity that met the discontinuation criteria during the initial treatment with ASP1948 or ASP1948 in combination with nivolumab.

Exclusion Criteria:

  • Subject weighs < 45 kg.
  • Subject has received investigational therapy (other than an investigational epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in a subject with EGFR 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, 2 mg per day of dexamethasone or up to 10 mg per day of prednisone) are allowed. Note: Corticosteroids for prophylaxis (e.g., contrast dye allergy) or for brief treatment of conditions not related to study treatment (e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is also 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 the subject is clinically stable and has no evidence of CNS progression by imaging for at least 28 days prior to start of study treatment and are not requiring immunosuppressive doses of systemic steroids (> 30 mg per day of hydrocortisone, > 2 mg per day of dexamethasone or > 10 mg per day of prednisone or equivalent) for longer than 14 days.
  • Subject has leptomeningeal disease as a manifestation of the current malignancy.
  • Subject has an active autoimmune disease. Subjects with type 1 diabetes mellitus, stable endocrinopathies maintained on appropriate replacement therapy and 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 ASP1948 or nivolumab or severe hypersensitivity reaction to treatment with another monoclonal antibody.
  • Subject with positive Hepatitis B virus antibodies and surface antigen (indicating acute Hepatitis B virus (HBV) or chronic HBV) or Hepatitis C (HCV ribonucleic acid (RNA) (qualitative)). Hepatitis C RNA testing is not required in subjects with negative Hepatitis C antibody testing. Hepatitis B virus antibodies are not required in subjects with negative Hepatitis B surface antigen.
  • 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 active infection requiring systemic therapy (e.g., intravenous antibiotics) within 14 days prior to study drug treatment.
  • Subject is expected to require another form of antineoplastic therapy while on study treatment.
  • Subject has an uncontrolled intercurrent illness including, but not limited to cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
  • Subject's AEs (excluding alopecia) from prior therapy have not improved to Grade 1 or baseline within 14 days prior to start of study treatment.
  • Subject has significant cardiovascular disease including:

    • Subject has inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications).
    • Subject has a history of myocardial infarction or unstable angina within 6 months prior to day 1.
    • Subject has New York Heart Association Class II or greater chronic heart failure (CHF).
    • History of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to study treatment.
    • Subject has significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study treatment.
  • Subject has a history of hemoptysis (bright red blood of ½ teaspoon or more per episode) within 12 weeks prior to study treatment.
  • Subject has evidence of a bleeding diathesis or significant coagulopathy.
  • Subject has inadequate recovery from prior surgical procedure or has had a major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1, or anticipates the need for a major surgical procedure during the course of the study or minor surgery within 7 days of starting study treatment.
  • Subject has initiated new treatment with medications that affect the coagulation cascade with an international normalized ratio (INR) ≥ 2 such as vitamin K antagonists, heparins and direct thrombin inhibitors or the use of factor Xa inhibitors within 28 days prior to the start of study treatment. Note: If the subject started receiving such medications more than 28 days prior to the start of study treatment and needs to continue, this is allowed. However, new anticoagulation may not be initiated within 28 days prior to the start of study treatment.
  • Subject has any condition that makes the subject unsuitable for study participation.

Additional Exclusion Criteria for Re-treatment:

  • Subjects who have completed 40 weeks of follow-up with disease control are not eligible for retreatment.
  • Subject currently has an ongoing Adverse Event (AE) related to the initial ASP1948 or ASP1948 in combination with nivolumab treatment that meets the criteria for treatment interruption or discontinuation.
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 Canada,   Korea, Republic of,   Taiwan,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03565445
Other Study ID Numbers  ICMJE 1948-CL-0101
2018-003873-82 ( 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: Yes
Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com/
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: Medical Monitor Astellas Pharma Global Development, Inc.
PRS Account Astellas Pharma Inc
Verification Date June 2020

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