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History of Changes for Study: NCT03799003
A Study of ASP1951 in Subjects With Advanced Solid Tumors
Latest version (submitted September 4, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 9, 2019 None (earliest Version on record)
2 January 23, 2019 Study Status
3 April 30, 2019 Study Status and Contacts/Locations
4 July 19, 2019 Study Status and Contacts/Locations
5 September 12, 2019 Arms and Interventions, Outcome Measures, Study Description, Study Status, Study Identification, Eligibility, Study Design and Conditions
6 January 8, 2020 Study Status and Contacts/Locations
7 March 9, 2020 Study Status
8 March 16, 2020 Contacts/Locations and Study Status
9 May 2, 2020 Recruitment Status, Study Status, Contacts/Locations and Study Description
10 June 12, 2020 Recruitment Status, Study Status, Contacts/Locations and Study Description
11 June 24, 2020 IPDSharing, Contacts/Locations and Study Status
12 July 8, 2020 Study Status and Contacts/Locations
13 July 23, 2020 Eligibility, Outcome Measures, Study Description, Sponsor/Collaborators, Study Status and Study Identification
14 August 24, 2020 Study Status
15 October 26, 2020 Study Status
16 November 25, 2020 Study Status
17 March 4, 2021 Study Status and Contacts/Locations
18 April 8, 2021 Study Status, Outcome Measures, Contacts/Locations, Eligibility, Arms and Interventions and Study Description
19 May 12, 2021 Study Status and Contacts/Locations
20 June 3, 2021 Contacts/Locations and Study Status
21 June 20, 2021 Study Status and Contacts/Locations
22 July 27, 2021 Study Status and Contacts/Locations
23 August 16, 2021 Study Status and Contacts/Locations
24 September 1, 2021 Contacts/Locations and Study Status
25 October 10, 2021 Study Status and Contacts/Locations
26 December 3, 2021 Study Status
27 January 18, 2022 Study Status and Eligibility
28 March 7, 2022 Study Status
29 April 19, 2022 Recruitment Status, Study Status, Contacts/Locations and Study Design
30 May 6, 2022 Study Status
31 June 9, 2022 Study Status
32 July 20, 2022 Study Status
33 September 4, 2022 Study Status
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Study NCT03799003
Submitted Date:  January 9, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: 1951-CL-0101
Brief Title: A Study of ASP1951 in Subjects With Advanced Solid Tumors
Official Title: A Phase 1 Study of ASP1951 in Subjects With Advanced Solid Tumors
Secondary IDs:
Open or close this module Study Status
Record Verification: January 2019
Overall Status: Recruiting
Study Start: December 19, 2018
Primary Completion: August 2023 [Anticipated]
Study Completion: August 2023 [Anticipated]
First Submitted: January 2, 2019
First Submitted that
Met QC Criteria:
January 9, 2019
First Posted: January 10, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
January 9, 2019
Last Update Posted: January 10, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Astellas Pharma Global Development, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary: The primary purpose of this study is to evaluate the tolerability and safety profile of ASP1951 in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile of ASP1951; and determine the recommended phase 2 dose (RP2D) of ASP1951 and/or maximum tolerated dose (MTD). This study will also evaluate the anti-tumor effect of ASP1951.
Detailed Description:

This is a dose-escalation and expansion study of ASP1951. The study consists of 3 periods: 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 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, colorectal cancer, prostate cancer and cervical cancer.

For dose expansion, the tumor-specific cohorts will include 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.

Open or close this module Conditions
Conditions: Advanced Solid Tumors
Keywords: ASP1951
cervical cancer
Oncology
squamous cell carcinoma of the head and neck (SCCHN)
Tumors
colorectal cancer
prostate cancer
Advanced (unresectable) or metastatic solid tumor malignancies
Advanced solid tumors
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Sequential Assignment
Number of Arms: 3
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 213 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: ASP1951 Dose 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).
Drug: ASP1951
Intravenously (IV)
Experimental: ASP1951 Dose Expansion
If a confirmed response (partial Response (PR) or complete response (CR)) 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 deemed tolerable.
Drug: ASP1951
Intravenously (IV)
Experimental: ASP1951 Optional Retreatment Period
Participants may reinitiate study drug treatment after confirmation that the participant meets all the re-treatment eligibility criteria.
Drug: ASP1951
Intravenously (IV)
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
Secondary Outcome Measures:
1. 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).
2. 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.
3. 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.
4. 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).
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the number of prior treatment regimens) that is confirmed by available pathology records or current biopsy as well as 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 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 non-small cell lung cancer (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. 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 56 days prior to first dose of study treatment.
  • 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.

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 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. 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 severe hypersensitivity reaction to treatment with another monoclonal antibody.
  • 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 4 weeks 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 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.
Open or close this module Contacts/Locations
Central Contact Person: Astellas Pharma Global Development, Inc.
Telephone: 800-888-7704
Email: astellas.registration@astellas.com
Study Officials: Medical Monitor
Study Director
Astellas Pharma Global Development, Inc.
Locations: United States, Texas
South Texas Accelerated Research Therapeutics, LLC
[Recruiting]
San Antonio, Texas, United States, 78229
Open or close this module IPDSharing
Plan to Share IPD: Undecided
Studies conducted with product indications or formulations that remain in development are assessed after study completion to determine if Individual Participant Data can be shared. The plan to share Individual Participant Data is based on the status of product approval or termination of the compound, in addition to other study-specific criteria described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."
Open or close this module References
Citations:
Links:
Available IPD/Information:

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