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A Study of ASP1951 in Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03799003
Recruitment Status : Recruiting
First Posted : January 10, 2019
Last Update Posted : January 25, 2019
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Drug: ASP1951 Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 213 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of ASP1951 in Subjects With Advanced Solid Tumors
Actual Study Start Date : January 14, 2019
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : August 2023

Arm Intervention/treatment
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)




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).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03799003


Contacts
Contact: Astellas Pharma Global Development, Inc. 800-888-7704 astellas.registration@astellas.com

Locations
United States, Texas
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Medical Monitor Astellas Pharma Global Development, Inc.

Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT03799003     History of Changes
Other Study ID Numbers: 1951-CL-0101
First Posted: January 10, 2019    Key Record Dates
Last Update Posted: January 25, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: 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."

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
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

Additional relevant MeSH terms:
Neoplasms