Small Cell Lung Cancer
Conditions
Keywords
AMG 119, CART, DLL3
Brief summary
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
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.
Interventions
BIOLOGICALAMG 119
Investigational, adoptive cellular immunotherapy for the treatment of small cell lung cancer
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| Measurement of expansion and persistence of CAR T cells in peripheral blood post-infusion | Up to 5 years |
| Objective Response (OR) | Up to 5 years |
| Evidence of CAR T cells in tumor tissue post dose | 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 |
Countries
United States
Outcome results
None listed