A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With RR SCLC

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase 1 Study Evaluating the Safety, Tolerability and Efficacy of AMG 119 in Subjects With Relapsed/Refractory Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Biological: AMG 119


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AMG 119 Treatment<br>AMG 119 administered as a one-time intravenous infusion at different cell dose levels | Biological: AMG 119<br>* Investigational, adoptive cellular immunotherapy for the treatment of small cell lung cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting toxicities (DLTs) |  | Up to 5 years | 
| Incidence of treatment-emergent adverse events and treatment-related adverse events |  | Up to 5 years | 
| Incidence of clinically significant changes in vital signs |  | Up to 5 years | 
| Incidence of clinically significant changes in physical examinations |  | Up to 5 years | 
| Incidence of clinically significant changes in clinical laboratory tests |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (OR) |  | Up to 5 years | 
| Duration of Response (DOR) |  | Up to 5 years | 
| Progression-Free Survival (PFS) |  | Up to 5 years | 
| 1-year Overall Survival (1-year OS) |  | Up to 5 years | 
| Overall Survival (OS) |  | Up to 5 years | 
| Measurement of expansion and persistence of CAR T cells in peripheral blood post-infusion |  | Up to 5 years | 
| Evidence of CAR T cells in tumor tissue post dose |  | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMG 119, CART, DLL3