cancer du poumon à petites cellules
AMG 757 + pembrolizumab
Evaluer l'efficacité et la tolérabilité du AMG 757 en combinaison avec le pembrolizumab
1) Subject has provided informed consent prior to initiation of any study-specific activities/procedures
2) Age ≥ 18 years old at the time of signing the informed consent
3) Histologically or cytologically confirmed SCLC
• Part A and Part C: RR SCLC who progressed or recurred following at least 1 platinum-based regimen;
• Part B: ED SCLC with ongoing clinical benefit (stable disease [SD], partial response [PR], or complete response [CR]) following no more than 6 cycles of first-line platinum-based chemotherapy with the last dose of chemotherapy ≥ 28 days prior to the study day 1 (first-line consolidation setting)
4) Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
5) Minimum life expectancy of 12 weeks
6) RR SCLC only: at least 2 measurable lesions as defined per modified RECIST 1.1 within 21 days prior to the first dose of AMG 757. Subjects with 1 measurable lesion may be considered for inclusion after discussion with the Medical Monitor.
7) Subjects with treated brain metastases are eligible provided they meet the following criteria:
• Definitive therapy was completed at least 2 weeks prior to the first dose of AMG 757
• There is no evidence of radiographic CNS progression 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 for at least 7 days (unless symptoms are deemed irreversible by the investigator), 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
8) Adequate organ function, defined as follows:
• Hematological function: Absolute neutrophil count ≥ 1X 109/L; Platelet count ≥ 100 X 109/L; Hemoglobin > 9 g/dL (90 g/L)
• Coagulation function: PT/INR and PTT or APTT ≤ 1.5 x Institutional Upper Limit of Normal. Patients on chronic anticoagulation therapy who do not meet the criteria above may be eligible to enroll after discussion with the Medical Monitor.
• Renal function as follows: Estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation > 60 mL/min/1.73 m2
• Hepatic function: AST, ALT and alkaline phosphatase < 3 X ULN (or < 5 X ULN for subjects with liver involvement); Total bilirubin < 1.5 X ULN (or < 2 X ULN for subjects with liver metastases)
• Pulmonary function: No clinically significant pleural effusion; Baseline oxygen saturation > 90% on room air
• Cardiac function: Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an ECHO or MUGA, and no clinically significant ECG findings
1) History of other malignancy within the past 2 years prior to first dose of AMG 757
2) Major surgery within 28 days of first dose AMG 757
3) Untreated or symptomatic brain metastases and leptomeningeal disease
4) Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of AMG 757
5) History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of first dose of AMG 757
6) Presence of fungal, bacterial, viral, or other infection requiring oral or IV antimicrobials for management within 7 days of first dose AMG 757
7) Subject has known sensitivity and immediate hypersensitivity to any components of AMG 757, or to pembrolizumab (Part C only)
8) Prior anti-cancer therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and first dose of AMG 757
9) Subjects who experienced severe, life-threatening or recurrent (Grade 2 or higher) immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents
10) Has evidence of interstitial lung disease or active, non-infectious pneumonitis
11) Presence of any indwelling line or drain
12) Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of AMG 757
13) Unresolved toxicity from prior anti-tumor therapy, defined as not having resolved to CTCAE version 4.0 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 > 21 day) 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
14) History of hypophysitis or pituitary dysfunction
15) Exclusion of hepatitis infection
16) Subjects of both genders of child-bearing potential who are not willing to practice an acceptable method(s) of effective birth control.
17) Females who are pregnant or planning to become pregnant or breastfeeding or who plan to breastfeed.
18) Males who are unwilling to abstain from sperm donation.
19) 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.
20) Live vaccination is not allowed for at least 4 weeks prior to the start of AMG 757 treatment, during treatment, and until end of last study dose.