A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC
A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC
A study to evaluate the safety and tolerability of AMG 119 in adult subjects with
 Relapsed/Refractory Small Cell Lung Cancer (SCLC) and determine the appropriate cell dose.
This is a phase 1, first-in-human study to evaluate the safety and tolerability of AMG 119,
 an investigational, Chimeric Antigen Receptor T cell therapy targeting delta-like protein 3
 (DLL3) in subjects with relapsed/refractory small cell lung cancer who progressed after at
 least 1 platinum based chemotherapy regimen.
Inclusion Criteria:

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

 -  Age ≥ 18 years old at the time of signing the informed consent

 -  Histologically or cytologically confirmed Small Cell Lung Cancer (SCLC) with
 radiographically documented disease progression or recurrence after at least one
 platinum-based regimen:

 -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

 -  At least 2 measurable lesions as defined per modified RECIST 1.1 by CT or MRI
 performed after the last line of anti-cancer therapy within 28 days of enrollment.
 Subjects with 1 measurable lesion may be considered upon agreement with Sponsor

 -  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 for at least 7 days.

 -  Adequate organ function

 -  Other inclusion criteria may apply

 Exclusion Criteria:

 -  History of other malignancy within the past 2 years prior to enrollment except:
 Malignancy (other than in situ) treated with curative intent and with no known active
 disease present for ≥ 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 in situ cancer without
 evidence of disease; Prostatic intraepithelial neoplasia without evidence of prostate
 cancer; Adequately treated urothelial papillary noninvasive carcinoma.

 -  History of organ transplant.

 -  Major surgery within 28 days of enrollment.

 -  Myocardial infarction and/or symptomatic congestive heart failure (New York Heart
 Association > class II) within 12 months of enrollment.

 -  History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12
 months of enrollment.

 -  Untreated or symptomatic brain metastases and leptomeningeal disease

 -  Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials
 for management within 7 days of enrollment. Note: Simple UTI and uncomplicated
 bacterial pharyngitis are permitted if responding to active treatment and after
 consultation with sponsor.

 -  Known sensitivity and immediate hypersensitivity to any components of AMG 119 or
 conditioning regimen (cyclophosphamide and fludarabine).

 -  Evidence of a bleeding diathesis.

 -  Systemic corticosteroid therapy within 7 days before enrollment. Note: Topical and
 inhaled corticosteroids in standard doses and physiologic replacement for subjects
 with adrenal insufficiency are allowed. ≥ 5 mg/day of prednisone or equivalent doses
 of other corticosteroids are not allowed.

 -  Prior anti-cancer therapy as specified below: At least 21 days from enrollment must
 have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule
 therapy (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB
 agonists, etc). Note: Patients who experienced immune -related pneumonitis, pituitary
 or thyroid dysfunction, or pancreatitis while on treatment with immune-oncology agents
 will be excluded; Other anti-cancer therapy (chemotherapy, antibody therapy, molecular
 targeted therapy, or investigational agent) within 14 days prior to enrollment;
 Radiation therapy completed within 14 days prior to enrollment; Prior CAR T therapy or
 other genetically modified T cell therapy with the exception of subjects who received
 AMG 119 in this study and are eligible for retreatment.

 -  Primary immunodeficiency

 -  History of autoimmune disease resulting in end organ injury or requiring systemic
 immunosuppression/systemic disease modifying agents within the last 2 years prior to
 enrollment

 -  Unresolved toxicities from prior anti-tumor therapy (defined as not having resolved to
 Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1, or to
 levels dictated in the eligibility criteria) with the exception of alopecia or
 toxicities from prior anti-tumor therapy that are considered irreversible [defined as
 having been present and stable for > 28 days] which may be allowed if they are not
 otherwise described in the exclusion criteria AND there is agreement to allow by both
 the investigator and Amgen

 -  Received live vaccine within 28 days prior to enrollment

 -  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

 -  History or evidence of any other clinically significant disorder, condition or disease
 that, in the opinion of the investigator or Amgen physician, if consulted, would pose
 a risk to subject safety or interfere with the study evaluation, procedures or
 completion

 -  Other exclusion criteria may apply