Clinical Trials /

A Study of ASP1948, Targeting an Immune Modulatory Receptor, in Subjects With Advanced Solid Tumors

NCT03565445

Description:

The purpose of this study is to evaluate the tolerability and safety profile of ASP1948 when administered as a single agent and in combination with nivolumab in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile of ASP1948 when administered as a single agent and in combination with nivolumab and determine the recommended Phase 2 dose (RP2D) of ASP1948 when administered as a single agent and in combination with nivolumab. This study will also evaluate the antitumor effect of ASP1948 when administered as a single agent and in combination with nivolumab.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of ASP1948, Targeting an Immune Modulatory Receptor, in Subjects With Advanced Solid Tumors
  • Official Title: A Phase 1b Study of ASP1948, Targeting an Immune Modulatory Receptor as a Single Agent and in Combination With Nivolumab in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 1948-CL-0101
  • NCT ID: NCT03565445

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
ASP1948ASP1948 plus nivolumab Combination Therapy
nivolumabASP1948 plus nivolumab Combination Therapy

Purpose

The purpose of this study is to evaluate the tolerability and safety profile of ASP1948 when administered as a single agent and in combination with nivolumab in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile of ASP1948 when administered as a single agent and in combination with nivolumab and determine the recommended Phase 2 dose (RP2D) of ASP1948 when administered as a single agent and in combination with nivolumab. This study will also evaluate the antitumor effect of ASP1948 when administered as a single agent and in combination with nivolumab.

Detailed Description

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

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

      After discontinuation of study drug, all participants will complete an end-of-treatment
      visit, along with 30-day and 90-day safety follow-up visits from the last dose of study drug.

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

Trial Arms

NameTypeDescriptionInterventions
ASP1948 Dose EscalationExperimentalThe monotherapy escalation cohort will evaluate escalating dose levels of ASP1948. Each dose level will enroll approximately 3 or 4 participants. Dose escalation to the next level will be made based on the Bayesian Continual Reassessment Method (CRM).
  • ASP1948
ASP1948 Dose ExpansionExperimentalIf a confirmed response (iRECIST partial response (iPR) or iRECIST confirmed response (iCR)) per iRECIST occurs in a monotherapy escalation cohort, a tumor specific expansion cohort may be opened in that tumor type, at the dose level in which the confirmed response was observed and at all subsequent dose levels once each dose level has been cleared. Up to 5 expansion cohorts may be opened.
  • ASP1948
ASP1948 Optional Retreatment PeriodExperimentalParticipants may reinitiate study drug treatment after confirmation that they meet all the re-treatment eligibility criteria.
  • ASP1948
ASP1948 plus nivolumab Combination TherapyExperimentalASP1948 will be administered in combination with a fixed dose of nivolumab every 2 weeks. ASP1948 dose for combination therapy escalation cohorts will start at one dose level below the most recently cleared dose in the monotherapy escalation cohort at the time of opening the combination therapy.
  • ASP1948
  • nivolumab

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, and has received all standard therapies (unless
             the therapy is contraindicated or intolerable) felt to provide clinical benefit.

          -  Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or
             2.

          -  Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was
             at least 21 days prior to initiation of study drug administration. A subject with
             epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)
             mutation-positive NSCLC is allowed to remain on EGFR tyrosine kinase inhibitor (TKI)
             or ALK inhibitor therapy until 4 days prior to the start of study drug administration.

          -  Subject has completed any radiotherapy (including stereotactic radiosurgery) at least
             14 days prior to study drug administration.

          -  Subject with metastatic castration-resistant prostate cancer (mCRPC) (positive scan
             and/or soft tissue disease documented by computed tomography/magnetic resonance
             imaging) meets both of the following:

               -  Subject has serum testosterone ≤ 50 ng/dL at screening.

               -  Subject has had an orchiectomy or plans to continue androgen deprivation therapy
                  (ADT) for the duration of study treatment.

          -  Subject has adequate organ function as indicated by laboratory values. (If a subject
             has received a recent blood transfusion, the laboratory tests must be obtained ≥ 28
             days after any blood transfusion.) Note: Growth factors, colony stimulating factors
             are not permitted in the screening period.

          -  Female subject must either:

               -  Be of non-childbearing potential: post-menopausal (defined as at least 1 year
                  without any menses for which there is no other obvious pathological or
                  physiological cause) prior to screening, or; documented surgically sterile (e.g.,
                  hysterectomy, bilateral salpingectomy, bilateral oophorectomy).

               -  Or, if of childbearing potential: Agree not to try to become pregnant during the
                  study treatment and for 6 months after the final study drug administration; and
                  have a negative urine or serum pregnancy test prior to study drug administration;
                  and if heterosexually active, agree to consistently use 1 form of highly
                  effective birth control starting at screening and throughout the study treatment
                  and 6 months after the final study drug administration.

          -  Female subject must agree not to breastfeed starting at screening and throughout the
             study treatment, and for 6 months after the final study drug administration.

          -  Female subject must not donate ova starting at screening and throughout the study
             treatment, and for 6 months after the final study drug administration.

          -  A sexually active male subject with female partner(s) who are of childbearing
             potential is eligible if :

               -  The male subject agrees to use a male condom starting at screening and continues
                  throughout the study treatment, and for 6 months after the final study drug
                  administration.

               -  The male subject has not had a vasectomy or is not sterile, as defined below and
                  the subject's female partner(s) is utilizing 1 form of highly effective birth
                  control starting at screening and continuing throughout the study treatment and
                  for 6 months after the final study drug administration.

          -  Male subject must not donate sperm starting at screening and throughout the study
             treatment, and for 6 months after the final study drug administration.

          -  Male subject with a pregnant or breastfeeding partner(s) must agree to remain
             abstinent or use a condom for the duration of the pregnancy or time partner is
             breastfeeding throughout the study treatment and for 6 months after the final study
             drug administration.

          -  Subject agrees not to participate in another interventional study while receiving
             study drug (subjects who are currently in the follow-up period of an interventional
             clinical trial are allowed).

        Additional Inclusion Criteria for Subjects in the Expansion Cohorts:

          -  Subject has at least 1 measureable lesion per RECIST 1.1. The measureable lesion must
             be outside the field of radiation if subject had prior radiotherapy. Subjects with
             mCRPC who do not have measurable lesions must have at least 1 of the following:

               -  Progression with 2 or more new bone lesions, or

               -  Prostate specific antigen (PSA) progression (defined as a minimum of 3 rising PSA
                  levels with an interval of ≥ 1 week between each determination) within 6 weeks
                  prior to study drug administration and a PSA value at the screening visit ≥ 2
                  ng/mL.

          -  Subject consents to provide available tumor specimen in a tissue block or unstained
             serial slides obtained within 8 to 56 days prior to first dose of study treatment.
             Note: This does not apply to subjects with mCRPC who do not have measurable disease.

          -  Subject is an appropriate candidate for tumor biopsy and consents to undergoing a
             tumor biopsy (core needle biopsy or excision) during the treatment period. Note: This
             does not apply to subjects with mCRPC who do not have measurable disease.

          -  Subject meets one of the following:

               -  Subject has the tumor type for which a confirmed response was observed in a
                  monotherapy or in combination with nivolumab dose escalation or RP2D cohort; or

               -  For an expansion cohort opened due to achieving predicted efficacious exposure,
                  subject has squamous cell carcinoma of the head and neck (SCCHN); or

               -  For RP2D monotherapy or in combination with nivolumab expansion cohorts, subject
                  has NSCLC, mCRPC, ovarian, pancreatic, or breast cancer.

        Additional Inclusion Criteria for Re-treatment:

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

          -  Subject stopped initial treatment with ASP1948 or ASP1948 in combination with
             nivolumab after attaining a confirmed CR or PR or SD.

          -  Subject experienced a confirmed disease progression by iRECIST (iCPD) (or unconfirmed
             progressive disease by iRECIST (iUPD) if subject is not clinically stable to await
             confirmatory scan) after stopping their initial treatment with ASP1948 or ASP1948 in
             combination with nivolumab.

          -  Subject did not receive any prohibited anti-cancer treatment since the last dose of
             ASP1948 or ASP1948 in combination with nivolumab.

          -  Subject did not experience a toxicity that met the discontinuation criteria during the
             initial treatment with ASP1948 or ASP1948 in combination with nivolumab.

        Exclusion Criteria:

          -  Subject weighs < 45 kg.

          -  Subject has received investigational therapy (other than an investigational epidermal
             growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in a subject with EGFR
             mutations or ALK inhibitor in a subject with an ALK mutation) within 21 days prior to
             start of study drug.

          -  Subject requires or has received systemic steroid therapy or any other
             immunosuppressive therapy within 14 days prior to study drug administration. Subjects
             using a physiologic replacement dose of hydrocortisone or its equivalent(defined as up
             to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone or up to 10 mg per
             day of prednisone) are allowed. Note: Corticosteroids for prophylaxis (e.g., contrast
             dye allergy) or for brief treatment of conditions not related to study treatment
             (e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is also
             allowed.

          -  Subject has symptomatic central nervous system (CNS) metastases or subject has
             evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans).
             Subjects with previously treated CNS metastases are eligible, if the subject is
             clinically stable and has no evidence of CNS progression by imaging for at least 28
             days prior to start of study treatment and are not requiring immunosuppressive doses
             of systemic steroids (> 30 mg per day of hydrocortisone, > 2 mg per day of
             dexamethasone or > 10 mg per day of prednisone or equivalent) for longer than 14 days.

          -  Subject has leptomeningeal disease as a manifestation of the current malignancy.

          -  Subject has an active autoimmune disease. Subjects with type 1 diabetes mellitus,
             stable endocrinopathies maintained on appropriate replacement therapy and skin
             disorders (e.g., vitiligo, psoriasis or alopecia) not requiring systemic treatment are
             allowed.

          -  Subject was discontinued from prior immunomodulatory therapy due to a Grade ≥ 3
             toxicity that was mechanistically related (e.g., immune related) to the agent.

          -  Subject has known history of serious hypersensitivity reaction to a known ingredient
             of ASP1948 or nivolumab or severe hypersensitivity reaction to treatment with another
             monoclonal antibody.

          -  Subject with positive Hepatitis B virus antibodies and surface antigen (indicating
             acute Hepatitis B virus (HBV) or chronic HBV) or Hepatitis C (HCV ribonucleic acid
             (RNA) (qualitative)). Hepatitis C RNA testing is not required in subjects with
             negative Hepatitis C antibody testing. Hepatitis B virus antibodies are not required
             in subjects with negative Hepatitis B surface antigen.

          -  Subject has received a live vaccine against infectious diseases within 28 days prior
             to initiation of study treatment.

          -  Subject has a history of drug-induced pneumonitis (interstitial lung disease) or
             currently has pneumonitis.

          -  Subject has an active infection requiring systemic therapy (e.g., intravenous
             antibiotics) within 14 days prior to study drug treatment.

          -  Subject is expected to require another form of antineoplastic therapy while on study
             treatment.

          -  Subject has an uncontrolled intercurrent illness including, but not limited to cardiac
             arrhythmia or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Subject's AEs (excluding alopecia) from prior therapy have not improved to Grade 1 or
             baseline within 14 days prior to start of study treatment.

          -  Subject has significant cardiovascular disease including:

               -  Subject has inadequately controlled hypertension (defined as systolic blood
                  pressure > 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive
                  medications).

               -  Subject has a history of myocardial infarction or unstable angina within 6 months
                  prior to day 1.

               -  Subject has New York Heart Association Class II or greater chronic heart failure
                  (CHF).

               -  History of cerebrovascular accident (CVA) or transient ischemic attack (TIA)
                  within 6 months prior to study treatment.

               -  Subject has significant vascular disease (e.g., aortic aneurysm requiring
                  surgical repair or recent peripheral arterial thrombosis) within 6 months prior
                  to study treatment.

          -  Subject has a history of hemoptysis (bright red blood of ½ teaspoon or more per
             episode) within 12 weeks prior to study treatment.

          -  Subject has evidence of a bleeding diathesis or significant coagulopathy.

          -  Subject has inadequate recovery from prior surgical procedure or has had a major
             surgical procedure, open biopsy or significant traumatic injury within 28 days prior
             to day 1, or anticipates the need for a major surgical procedure during the course of
             the study or minor surgery within 7 days of starting study treatment.

          -  Subject has initiated new treatment with medications that affect the coagulation
             cascade with an international normalized ratio (INR) ≥ 2 such as vitamin K
             antagonists, heparins and direct thrombin inhibitors or the use of factor Xa
             inhibitors within 28 days prior to the start of study treatment. Note: If the subject
             started receiving such medications more than 28 days prior to the start of study
             treatment and needs to continue, this is allowed. However, new anticoagulation may not
             be initiated within 28 days prior to the start of study treatment.

          -  Subject has any condition that makes the subject unsuitable for study participation.

        Additional Exclusion Criteria for Re-treatment:

          -  Subjects who have completed 40 weeks of follow-up with disease control are not
             eligible for retreatment.

          -  Subject currently has an ongoing Adverse Event (AE) related to the initial ASP1948 or
             ASP1948 in combination with nivolumab treatment that meets the criteria for treatment
             interruption or discontinuation.
      
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 toxicities (DLTs)
Time Frame:Up to 28 days
Safety Issue:
Description: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.

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 a maximum of 93 weeks
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 a maximum of 93 weeks
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 a maximum of 93 weeks
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 a maximum of 93 weeks
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

  • NSCLC
  • Tumors
  • squamous cell carcinoma of the head and neck (SCCHN)
  • Oncology
  • breast cancer
  • ASP1948
  • mCRPC
  • ovarian cancer
  • Locally advanced or metastatic solid tumor malignancies
  • pancreatic cancer
  • Advanced solid tumors

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