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.
- Subject has provided informed consent prior to initiation of any study specific
- 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
- 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
- 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.
- Disease Related. Primary brain tumor, untreated or symptomatic brain metastases and
- 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,
- 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
- 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.