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A Study of ASP1951 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: NCT03799003
Recruitment Status : Recruiting
First Posted : January 10, 2019
Last Update Posted : July 27, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE January 2, 2019
First Posted Date  ICMJE January 10, 2019
Last Update Posted Date July 27, 2020
Actual Study Start Date  ICMJE January 14, 2019
Estimated Primary Completion Date August 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2020)
  • Safety and tolerability assessed by Dose Limiting Toxicity (DLT) [ Time Frame: Up to 4 years ]
    A DLT is defined as any of the prespecified Adverse Events (AEs) (graded using National Cancer Institute Common Terminology 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 4 years ]
    Initial and retreatment. An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. 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 whether or not considered related to the medicinal product. AEs will be coded using the medical dictionary for regulatory activities (MedDRA) and graded using NCI-CTCAE 4.03.
  • Safety and tolerability assessed by immune-related AEs (irAEs) [ Time Frame: Up to 4 years ]
    Initial and retreatment. Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies (hypophysitis, hypothyroidism, hyperthyroidism, adrenal insufficiency and Type 1 diabetes mellitus). In the event a participant is diagnosed with an irAE, then it should be reported as an AE.
  • Safety and tolerability assessed by infusion-related reactions (IRRs) [ Time Frame: Up to 4 years ]
    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 4 years ]
    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 related to treatment [ Time Frame: Up to 4 years ]
    Initial and retreatment. Number of participants with potentially clinically significant laboratory values.
  • Safety and tolerability assessed by 12- lead electrocardiogram (ECG) [ Time Frame: Up to 4 years ]
    Initial and retreatment. ECGs should be obtained after the participant has rested in supine position (or semi-recumbent, if supine is not tolerated) for 10 minutes. Any clinically significant adverse changes on the ECG will be reported as AEs.
  • Number of participants with vital signs abnormalities and/or adverse events related to treatment [ Time Frame: Up to 4 years ]
    Initial and retreatment. Number of participants with potentially clinically significant vital sign values.
  • Number of participants with Physical Exam abnormalities and/or adverse events related to treatment [ Time Frame: Up to 4 years ]
    Initial and retreatment. Number of participants with potentially clinically significant physical exam values.
  • Safety and tolerability assessed by ECOG performance status [ Time Frame: Up to 4 years ]
    Initial and retreatment. The Eastern Cooperative Oncology Group (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 ASP1951 in serum: AUClast [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Area under the concentration time curve from the time of dosing to the last measurable concentration (AUClast) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: AUCinf [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: AUCinf%extrap [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf %extrap) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: AUCtau [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Area under the concentration time curve from the time of dosing to the start of next dosing interval (AUCtau) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: Cmax [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Maximum concentration (Cmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: Ctrough [ Time Frame: Up to 48 weeks ]
    Initial monotherapy escalation and retreatment. Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: tmax [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Time of the maximum concentration (tmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: t 1/2 [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Terminal elimination half-life (t1/2) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: tlast [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Time of last measurable concentration (tlast) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: CL [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Total clearance after intravenous dosing (CL) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: Vz [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Volume of distribution after intravenous dosing during the terminal elimination phase (Vz) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: Vss [ Time Frame: Up to 10 weeks ]
    Initial monotherapy escalation treatment only. Volume of distribution at steady state after intravenous dosing (Vss) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUClast [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Area under the concentration time curve from the time of dosing to the last measurable concentration (AUClast) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUCinf [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Area under the concentration time curve from the time of dosing extrapolated to time infinity (AUCinf) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUCinf%extrap [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Percentage of AUCinf due to extrapolation from time of the last measurable concentration to time infinity (AUCinf %extrap) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: AUCtau [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Area under the concentration time curve from the time of dosing to the start of next dosing interval (AUCtau) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Cmax [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Maximum concentration (Cmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Ctrough [ Time Frame: Up to 48 weeks ]
    Initial combination escalation and retreatment. Concentration immediately prior to dosing at multiple dosing (Ctrough) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: tmax [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Time of the maximum concentration (tmax) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: t 1/2 [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Terminal elimination half-life (t1/2) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: tlast [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Time of last measurable concentration (tlast) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: CL [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Total clearance after intravenous dosing (CL) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Vz [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Volume of distribution after intravenous dosing during the terminal elimination phase (Vz) will be recorded from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in combination with pembrolizumab in serum: Vss [ Time Frame: Up to 10 weeks ]
    Initial combination escalation treatment only. Volume of distribution at steady state after intravenous dosing (Vss) will be recorded from the pharmacokinetic (PK) serum samples collected.
Original Primary Outcome Measures  ICMJE
 (submitted: January 9, 2019)
  • Safety and tolerability assessed by Dose Limiting Toxicity (DLT) [ Time Frame: Up to 4 years ]
    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 4 years ]
    Initial and retreatment. An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. 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 whether or not considered related to the medicinal product. AEs will be coded using the medical dictionary for regulatory activities (MedDRA) and graded using NCI-CTCAE 4.03.
  • Safety and tolerability assessed by immune-related AEs (irAEs) [ Time Frame: Up to 4 years ]
    Initial and retreatment. Most frequent immune-related AEs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies (hypophysitis, hypothyroidism, hyperthyroidism, adrenal insufficiency and Type 1 diabetes mellitus). In the event a participant is diagnosed with an irAE, then it should be reported as an AE.
  • Safety and tolerability assessed by infusion-related reactions (IRRs) [ Time Frame: Up to 4 years ]
    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 4 years ]
    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 related to treatment [ Time Frame: Up to 4 years ]
    Initial and retreatment. Number of participants with potentially clinically significant laboratory values.
  • Safety and tolerability assessed by 12- lead electrocardiogram (ECG) [ Time Frame: Up to 4 years ]
    Initial and retreatment. ECGs should be obtained after the participant has rested in supine position (or semi-recumbent, if supine is not tolerated) for 10 minutes. Any clinically significant adverse changes on the ECG will be reported as AEs.
  • Number of participants with vital signs abnormalities and/or adverse events related to treatment [ Time Frame: Up to 4 years ]
    Initial and retreatment. Number of participants with potentially clinically significant vital sign values.
  • Number of participants with Physical Exam abnormalities and/or adverse events related to treatment [ Time Frame: Up to 4 years ]
    Initial and retreatment. Number of participants with potentially clinically significant physical exam values.
  • Safety and tolerability assessed by ECOG performance status [ Time Frame: Up to 4 years ]
    Initial and retreatment. The Eastern Cooperative Oncology Group (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 ASP1951 in serum: AUClast [ Time Frame: Up to 10 weeks ]
    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 ASP1951 in serum: AUCinf [ Time Frame: Up to 10 weeks ]
    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 ASP1951 in serum: AUCinf%extrap [ Time Frame: Up to 10 weeks ]
    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 ASP1951 in serum: AUCtau [ Time Frame: Up to 10 weeks ]
    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 ASP1951 in serum: Cmax [ Time Frame: Up to 10 weeks ]
    Initial dose escalation treatment only. Maximum concentration (Cmax) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: Ctrough [ Time Frame: Up to 48 weeks ]
    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 ASP1951 in serum: tmax [ Time Frame: Up to 10 weeks ]
    Initial dose escalation treatment only. Time of the maximum concentration (tmax) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: t 1/2 [ Time Frame: Up to 10 weeks ]
    Initial dose escalation treatment only. Terminal elimination half-life (t1/2) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: tlast [ Time Frame: Up to 10 weeks ]
    Initial dose escalation treatment only. Time of last measurable concentration (tlast) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: CL [ Time Frame: Up to 10 weeks ]
    Initial dose escalation treatment only. Total clearance after intravenous dosing (CL) will be derived from the pharmacokinetic (PK) serum samples collected.
  • Pharmacokinetics (PK) of ASP1951 in serum: Vz [ Time Frame: Up to 10 weeks ]
    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 ASP1951 in serum: Vss [ Time Frame: Up to 10 weeks ]
    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: January 9, 2019)
  • 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 4 years ]
    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 4 years ]
    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 4 years ]
    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 4 years ]
    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).
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 Study of ASP1951 in Subjects With Advanced Solid Tumors
Official Title  ICMJE A Phase 1b Study of ASP1951, a GITR Agonistic Antibody, 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 ASP1951 when administered as a single agent and in combination with pembrolizumab in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile of ASP1951 when administered as a single agent and in combination with pembrolizumab; and determine the recommended phase 2 dose (RP2D) of ASP1951 and/or maximum tolerated dose (MTD) when administered as a single agent and in combination with pembrolizumab. This study will also evaluate the anti-tumor effect of ASP1951 when administered as a single agent and in combination with pembrolizumab.
Detailed Description

This is a dose-escalation and expansion study of ASP1951. 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 monotherapy escalation cohorts will evaluate escalating dose levels of ASP1951 in participants with locally advanced (unresectable) or metastatic solid tumor malignancies including but not limited to squamous cell carcinoma of the head and neck (SCCHN), colorectal cancer, metastatic castration-resistant prostate cancer (mCRPC) and cervical cancer.

The combination escalation cohorts will evaluate escalating dose levels of ASP1951 in combination with a fixed dose of pembrolizumab.

For dose expansion, the tumor-specific cohorts will include participants with squamous cell carcinoma of the head and neck (SCCHN), melanoma, non-small cell lung cancer (NSCLC), colorectal and cervical cancer, as well as participants with any tumor types that respond to study drug treatment during dose escalation.

Participants may reinitiate study drug treatment in the optional Re-treatment period after confirmation that the participant meets all the re-treatment eligibility criteria.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE
  • Drug: ASP1951
    Intravenously (IV)
  • Drug: pembrolizumab
    Intravenously (IV)
Study Arms  ICMJE
  • Experimental: ASP1951 Monotherapy Escalation
    The monotherapy escalation cohort will evaluate escalating dose levels of ASP1951.Dose escalation to the next level will be made based on the Bayesian Continual Reassessment Method (CRM).
    Intervention: Drug: ASP1951
  • Experimental: ASP1951 Monotherapy Expansion
    If a confirmed response (partial Response (PR) or complete response (CR)) occurs in a monotherapy or combination 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 deemed tolerable.
    Intervention: Drug: ASP1951
  • Experimental: ASP1951 Optional Monotherapy Retreatment Period
    Participants may reinitiate study drug treatment after confirmation that the participant meets all the re-treatment eligibility criteria.
    Intervention: Drug: ASP1951
  • Experimental: ASP1951 plus pembrolizumab Combination Escalation
    The combination escalation cohort will evaluate escalating dose levels of ASP1951 in combination with a fixed dose of pembrolizumab. Dose escalation to the next level will be made based on the Bayesian Continual Reassessment Method (CRM).
    Interventions:
    • Drug: ASP1951
    • Drug: pembrolizumab
  • Experimental: ASP1951 plus pembrolizumab Combination Expansion
    If a confirmed response (partial Response (PR) or complete response (CR)) occurs in the combination 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 deemed tolerable.
    Interventions:
    • Drug: ASP1951
    • Drug: pembrolizumab
  • Experimental: ASP1951 plus pembrolizumab Optional Retreatment Period
    Participants may reinitiate study drug treatment after confirmation that the participant meets all the re-treatment eligibility criteria.
    Interventions:
    • Drug: ASP1951
    • 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: September 12, 2019)
435
Original Estimated Enrollment  ICMJE
 (submitted: January 9, 2019)
213
Estimated Study Completion Date  ICMJE August 2023
Estimated Primary Completion Date August 2023   (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 the following:

    • Subject in the escalation cohort has received all standard therapies (unless the therapy is contraindicated or intolerable) felt to provide clinical benefit the subject's specific tumor type. OR
    • Subject in an expansion cohort has received at least 1 standard therapy 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 21 days or 5-half-lives, whichever is shorter, 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 2 weeks prior to study drug administration.
  • Subject's AEs (excluding alopecia) from prior therapy have improved to grade 1 or baseline within 2 weeks 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 a bilateral 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. If a subject has received a recent blood transfusion, the laboratory tests must be obtained ≥ 4 weeks after any blood transfusion.
  • A 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); OR
    • 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 during the treatment period and for at least 6 months after the final study drug administration.
  • A male subject must not donate sperm during the treatment period and for at least 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 period 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. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Subjects with mC RPC 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 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 tissue biopsy or excision) during the treatment period as indicated in the Schedule of Assessments. 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 combination therapy cohort; or
    • Subject has SCCHN and a combination therapy expansion cohort is opened due to achieving the predicted efficacious exposure or
    • Subject has NSCLC, SCCHN, colorectal cancer, melanoma or cervical cancer and RP2D combination therapy expansion cohorts are opened.

Additional Inclusion Criteria for Re-treatment:

  • Subject stopped initial treatment with ASP1951 or ASP1951 in combination with pembrolizumab after attaining a confirmed CR, PR or SD.
  • Subject experienced an investigator-determined iCPD after stopping their initial treatment with ASP1951 or ASP1951 in combination with pembrolizumab.
  • Subject did not receive any prohibited anti-cancer treatment since the last dose of ASP1951 or ASP1951 in combination with pembrolizumab.
  • Subject did not experience a toxicity that met treatment discontinuation criteria during the initial treatment with ASP1951 or ASP1951 in combination with pembrolizumab or pembrolizumab alone.

Exclusion Criteria:

  • Subject weighs < 45 kg.
  • Subject has received investigational therapy (other than an investigational EGFR TKI in a subject with EGFR activating mutations or ALK inhibitor in a subject with an ALK mutation) within 21 days or 5-half-lives, whichever is shorter, 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.
  • 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 they are 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, > 2 mg per day of dexamethasone, or > 10 mg per day of prednisone or equivalent) for longer than 2 weeks.
  • Subject has leptomeningeal disease as a manifestation of the current malignancy.
  • Subject has an active autoimmune disease that has required systemic treatment in the past 2 years. Subjects with type 1 diabetes mellitus, endocrinopathies stably 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 ASP1951 or pembrolizumab or severe hypersensitivity reaction to treatment with another monoclonal antibody.
  • Subject with positive Hepatitis B virus (HBV) antibodies and surface antigen (indicating 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. HBV antibodies are not required in subjects with negative HBV surface antigen.
  • Subject has received a live vaccine against infectious diseases within 4 weeks prior to initiation of study treatment.
  • Subject has a history of drug-induced pneumonitis (interstitial lung disease), a history of (non-infectious) pneumonitis that required steroids, radiation pneumonitis or currently has pneumonitis.
  • Subject has an infection requiring systemic therapy within 2 weeks prior to study drug administration.
  • 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.
  • Subject has received prior treatment with an anti-glucocorticoid-induced tumor necrosis factor receptor (GITR) antibody.
  • Subject has had a major surgical procedure and has not completely recovered within 28 days prior to the start of study treatment.
  • Subject has any condition which makes the subject unsuitable for study participation.

Additional Exclusion Criterion for Subjects in Expansion Cohorts:

  • Subject has a prior malignancy, other than the current malignancy for which the subject is seeking treatment, active (i.e., requiring treatment of intervention) within the previous 2 years except for locally curable malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.

Additional Exclusion Criteria for Re-treatment:

  • Subjects who have completed 45 weeks in monotherapy or 57 weeks in combination therapy follow-up with disease control are not eligible for re-treatment.
  • Subject currently has an ongoing AE related to ASP1951 or ASP1951 in combination with pembrolizumab 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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03799003
Other Study ID Numbers  ICMJE 1951-CL-0101
2019-002287-27 ( EudraCT Number )
KEYNOTE KN-B02 ( Other Identifier: Merck )
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 Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Medical Monitor Astellas Pharma Global Development, Inc.
PRS Account Astellas Pharma Inc
Verification Date July 2020

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