Clinical Trials /

AMG 404 in Patients With Advanced Solid Tumors.

NCT03853109

Description:

To evaluate the safety and tolerability of AMG 404, a monoclonal antibody that binds to PD-1 and inhibits its engagement with ligands, in patients with advanced solid tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: AMG 404 in Patients With Advanced Solid Tumors.
  • Official Title: A Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 404, a Programmed Death-1 (PD-1) Antibody, in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: 20180143
  • NCT ID: NCT03853109

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
AMG 404Cohort 1

Purpose

To evaluate the safety and tolerability of AMG 404, a monoclonal antibody that binds to PD-1 and inhibits its engagement with ligands, in patients with advanced solid tumors.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1ExperimentalCohort 1
  • AMG 404
Cohort 2ExperimentalCohort 2
  • AMG 404
Cohort 3ExperimentalCohort 3
  • AMG 404
Cohort 4ExperimentalCohort 4
  • AMG 404

Eligibility Criteria

        Inclusion Criteria:

          -  Subject has provided informed consent prior to initiation of any study specific
             activities/procedures.

          -  Age greater than or equal to 18 years old at the time of signing informed consent.

          -  Life expectancy of greater than 3 months, in the opinion of the investigator

          -  Subject must have histologically or cytologically confirmed metastatic or locally
             advanced solid tumors not amenable to curative treatment with surgery or radiation for
             which:No standard therapy exists, or, Standard therapy has failed or is not available,
             or, In the investigator's opinion, standard therapy does not result in meaningful
             clinical benefit.

          -  At least 1 measurable or evaluable lesion as defined by RECIST 1.1 guidelines.

          -  Subjects with treated brain metastases are eligible provided they meet the following
             criteria: Definitive therapy was completed at least 2 weeks prior to enrollment. No
             evidence of radiographic CNS progression or CNS disease following definitive therapy
             and by the time of study screening. Patients manifesting progression in lesions
             previously treated with stereotactic radiosurgery may still be eligible if
             pseudoprogression can be demonstrated by appropriate means and after discussion with
             the medical monitor.

          -  Any CNS disease is asymptomatic, any neurologic symptoms due to CNS disease have
             returned to baseline or are deemed irreversible, the patient is off steroids for at
             least 7 days (physiologic doses of steroids are permitted), and the patient is off or
             on stable doses of anti-epileptic drugs for malignant CNS disease.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to
             2.

          -  Hematologic function, as follows without growth factor support within 2 weeks prior to
             study day 1: Absolute neutrophil count (ANC) greater than or equal to 1.0 x 10E9/L;
             Platelet count greater than or equal to 75 x 10E9/L; Hemoglobin greater than or equal
             to 9 g/dL (90 g/L).

          -  Adequate renal laboratory assessments, as follows: Estimated glomerular filtration
             rate based on MDRD (Modification of Diet in Renal Disease) calculation greater than or
             equal to 60 ml/min/1.73 m2.

          -  Hepatic function, as follows: Total bilirubin less than or equal to 1.5 x ULN or less
             than or equal to 3 x ULN for subjects with liver metástasis; AST less than or equal to
             3 x ULN or less than or equal to' 5 x ULN for subjects with liver metástasis; ALT less
             than or equal to 3 x ULN or less than or equal to 5 x ULN for subjects with liver
             metástasis; lkaline phosphatase less than or equal to 2.5 x ULN or less than or equal
             to 5 x ULN for subjects with liver metastasis.

        Exclusion Criteria:

          -  Disease Related. Primary brain tumor, untreated or symptomatic brain metastases and
             leptomeningeal disease

          -  Other Medical Conditions. History of other malignancy within the past 2 years, with
             the following exception[s]: Malignancy treated with curative intent and with no known
             active disease present for greater than or equal to 2 years before enrollment and felt
             to be at low risk for recurrence by the treating physician. Adequately treated
             non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately
             treated cervical carcinoma in situ without evidence of disease. Adequately treated
             breast ductal carcinoma in situ without evidence of disease. Prostatic intraepithelial
             neoplasia without evidence of prostate cancer. Adequately treated urothelial papillary
             noninvasive carcinoma or carcinoma in situ.

          -  History of solid organ transplantation.

          -  Major surgery within 28 days of study day 1.

          -  Prior/Concomitant Therapy: Prior treatment with anti-programmed death 1 (PD-1),
             anti-PD-L1, CTLA-4 or other checkpoint inhibitor drugs.

          -  Anti-tumor therapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted
             therapy, or investigational agent) within 21 days prior to study day 1. Note:
             Palliative radiotherapy is permitted.

          -  Live vaccine therapy within 4 weeks prior to study drug administration.

          -  Current treatment or within 14 days of day 1 with immunosuppressive corticosteroid
             defined as greater than 10 mg prednisone daily or equivalent. Corticosteroids with no
             or minimal systemic effect (such as topical or inhalation) are permitted.

          -  Prior/Concurrent Clinical Study Experience: Currently receiving treatment in another
             investigational device or drug study, or ess than 21 days prior to study day 1 since
             ending treatment on another investigational device or drug study(ies).

          -  Diagnostic Assessments: Evidence of interstitial lung disease or active,
             non-infectious pneumonitis.

          -  History of any immune-related colitis. Infectious colitis is allowed if evidence of
             adequate treatment and clinical recovery exists and at least 3 months interval
             observed since diagnosis of colitis.

          -  History of allergic reactions or acute hypersensitivity reaction to antibody
             therapies.

          -  Positive test for Human Immunodeficiency Virus (HIV).

          -  Exclusion of hepatitis infection based on the following results and/or criteria:
             Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or
             recent acute hepatitis B). Negative HBsAg and positive for hepatitis B core antibody:
             Hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable
             hepatitis B virus DNA suggests occult hepatitis B.

          -  Positive Hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is
             necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.

          -  Active infection requiring systemic therapy.

          -  Active or history of any autoimmune disease or immunodeficiencies. Subjects with Type
             I diabetes, vitiligo, psoriasis, hypo- or hyper- thyroid disease not requiring
             immunosuppressive treatment are permitted.

          -  Myocardial infarction within 6 months of study day 1, symptomatic congestive heart
             failure (New York Heart Association greater than class II), unstable angina, or
             cardiac arrhythmia requiring medication.

          -  Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to
             Common herminology Criteria for Adverse Events (CTCAE) versión 5.0 grade 1, or are
             stable and well controlled with minimal, local, or non-invasive intervention AND there
             is agreement to allow by both the investigator and the Amgen Medical Monitor.
      
Maximum Eligible Age:100 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Subject incidence of Dose limiting toxicities (DLTs)
Time Frame:28 Days
Safety Issue:
Description:Dose limiting toxicities (DLTs)

Secondary Outcome Measures

Measure:QT interval relationship
Time Frame:24 months
Safety Issue:
Description:Evaluate relationship between QT interval and AMG 404 exposure
Measure:Subject incidence of anti-AMG 404 antibodies
Time Frame:24 months
Safety Issue:
Description:Assess immunogenicity
Measure:Maximum observed concentration (Cmax) of AMG 404
Time Frame:24 months
Safety Issue:
Description:Pharmacokinetic (PK) analysis of AMG 404
Measure:Time of maximum observed concentration (Tmax) of AMG 404
Time Frame:24 months
Safety Issue:
Description:Pharmacokinetic (PK) analysis of AMG 404
Measure:Area under the serum concentration-time curve (AUC) of AMG 404
Time Frame:24 months
Safety Issue:
Description:Pharmacokinetic (PK) analysis of AMG 404

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

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