MC# 19-02 - A Phase I Study of ASP1948, Targeting an Immune Modulatory Receptor, in Subjects with Advanced Solid Tumors

  • Agent(s): ASP1948
  • Disease Type(s): Melanoma, Lung-NSCLC, Squamous Cell Carcinoma of Head and Neck, Prostate, Ovarian, Breast
  • Phase(s): I
  • Drug Classification(s): Targeted Therapy, Immunotherapy, Monoclonal Antibody
  • Molecular Target(s): NRP1

Mechanism of Action

ASP1948, a fully human monoclonal antibody that targets NRP1 expressing intra-tumoral Tregs affecting their stability/viability and hindering their suppression function.

Purpose

In this study, the sponsor and investigators want to learn:

  • How much of ASP1948 can be given with an acceptable level of side effects
  • About the safety and tolerability of ASP1948
  • How much of ASP1948 is absorbed into the blood and how fast it is removed
  • If research tests can be used in the future to predict who will benefit from ASP1948
  • How proteins that indicate the status of your disease are affected with use of ASP1948
  • If your body develops proteins that work against ASP1948
  • If ASP1948 prevents or delays tumor growth or shrinks an existing tumor
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) mutation-positive non-small cell lung cancer (NSCLC) is allowed to remain on EGFR tyrosine kinase inhibitor (TKI) 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.)
  • 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
  • Subject with squamous cell carcinoma of the head and neck (SCCHN), melanoma and breast cancer, is an appropriate candidate for tumor biopsy and consents to undergoing a tumor biopsy (core needle biopsy or excision) during the treatment period

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 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 the subjects initial treatment with ASP1948
    • Subject did not receive any prohibited anti-cancer treatment since the last dose of ASP1948
    • Subject did not experience a toxicity that met the discontinuation criteria during the initial treatment with ASP1948
Exclusion Criteria
  • 18 years or older
  • 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) 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 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 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); subject with negative Hepatitis C antibody testing may not need RNA testing
  • 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 received 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
  • Subject has any condition that makes the subject unsuitable for study participation

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT03565445

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Re: MC# 19-02