Clinical Trials /

A Study of ASP1951 in Subjects With Advanced Solid Tumors

NCT03799003

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of ASP1951 in Subjects With Advanced Solid Tumors
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 1951-CL-0101
  • SECONDARY ID: 2019-002287-27
  • SECONDARY ID: KEYNOTE KN-B02
  • NCT ID: NCT03799003

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
ASP1951ASP1951 Monotherapy Escalation
pembrolizumabASP1951 plus pembrolizumab Combination Escalation

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
ASP1951 Monotherapy EscalationExperimentalThe 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).
  • ASP1951
ASP1951 Monotherapy ExpansionExperimentalIf 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.
  • ASP1951
ASP1951 Optional Monotherapy Retreatment PeriodExperimentalParticipants may reinitiate study drug treatment after confirmation that the participant meets all the re-treatment eligibility criteria.
  • ASP1951
ASP1951 plus pembrolizumab Combination EscalationExperimentalThe 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).
  • ASP1951
  • pembrolizumab
ASP1951 plus pembrolizumab Combination ExpansionExperimentalIf 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.
  • ASP1951
  • pembrolizumab
ASP1951 plus pembrolizumab Optional Retreatment PeriodExperimentalParticipants may reinitiate study drug treatment after confirmation that the participant meets all the re-treatment eligibility criteria.
  • ASP1951
  • pembrolizumab

Eligibility 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
             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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability assessed by Dose Limiting Toxicity (DLT)
Time Frame:Up to 4 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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).
Measure:Duration of Response (DOR) per RECIST V1.1 and iRECIST
Time Frame:Up to 4 years
Safety Issue:
Description: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.
Measure:Persistence of response after discontinuation per RECIST V1.1 and iRECIST
Time Frame:Up to 4 years
Safety Issue:
Description: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.
Measure:Disease Control Rate (DCR) per RECIST V1.1 and iRECIST
Time Frame:Up to 4 years
Safety Issue:
Description: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).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial Keywords

  • ASP1951
  • cervical cancer
  • Oncology
  • squamous cell carcinoma of the head and neck (SCCHN)
  • metastatic castration-resistant prostate cancer (mCRPC)
  • melanoma
  • Tumors
  • pembrolizumab
  • colorectal cancer
  • Advanced (unresectable) or metastatic solid tumor malignancies
  • Advanced solid tumors

Last Updated

July 23, 2020