Etude : AMGEN 20190009 / CodeBreak 200



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Acronyme / Nom
Situation thérapeutique
Traitement
Cadre réglementaire
MÀJ
Présentation de l'étude
Acronyme / Nom : AMGEN 20190009 / CodeBreak 200

Situation thérapeutique : Métastatique ou localement avancé

Traitement : Thérapie ciblée

Cadre réglementaire : RIPH1

Dernière MÀJ : 30/11/2021
Titre
Spécialité(s)
CIM10 - Localisation(s)
Informations principales
Titre : A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated KRAS p.G12C

Spécialité : Organes respiratoires et intrathoraciques
Localisation : C34 - Tumeur maligne des bronches et du poumon
Schéma
Phase
Stade
Ligne(s)
Informations complémentaires
Schéma : STUDY ARMS:
- Experimental: AMG 510 - 21 day cycles
- Active Comparator: Docetaxel - 21 day cycles

MAIN OBJECTIVE:
To compare the efficacy of AMG 510 versus docetaxel as assessed by progression-free survival (PFS) in previously treated subjects with KRAS p.G12C mutated nonsmall cell lung cancer (NSCLC)

SECONDARY OBJECTIVES:
•To compare the efficacy of AMG 510 Versus docetaxel as assessed by:
- Overall Survival (OS)
- Objective response rate (ORR)
•To compare patient-reported outcomes (PRO) as assessed by:
- European Organization for Research and Treatment of Cancer Quality of life Questionnaire Core 13 (EORTC QLQ-LC13) and European Organization for Research and Treatment of Cancer Quality-of-life
Questionnaire Core 30 (EORTC QLQ-C30)
•To compare efficacy of AMG 510 versus docetaxel as assessed by:
- duration of response (DOR), time to response (TTR), and disease control rate (DCR)
•To compare the safety and tolerability of AMG 510 versus docetaxel
•To compare the effect of treatment with AMG 510 on other treatment
and disease related symptoms, and health related quality of life relative to docetaxel
•To characterize the pharmacokinetics (PK) of AMG 510 and its major metabolites

Phase : III

Stade : Localement avancé à Métastatique

2, 3, 4
Informations libres de droit
Critères d'inclusion
Critères de non-inclusion
Informations libres de droit
Critères d'inclusion et de non-inclusion
Critères d'inclusion : • Subject or subject's legally acceptable representative has provided informed consent prior to initiation of any study specific activities/procedures.
• Age ≥ 18 years of age
• Have documentation of KRAS p.G12C mutation confirmed by central
testing through the current protocol or Amgen Study 20190294 prior to enrollment.
• Subjects will have received and progressed or experienced disease recurrence on or after receiving at least 1 prior systemic therapy for locally advanced and unresectable or metastatic disease. Prior treatment must include a platinum-based doublet chemotherapy and checkpoint inhibitor for advanced or metastatic disease, either given as one line of therapy or as individual lines of therapy unless the subject has a medical contraindication to one of the required therapies. If the subject has a medical contraindication to a required therapy, the subject may be enrolled only after the investigator discusses and obtains approval from the Amgen medical monitor.
a) Adjuvant therapy will count as a line of therapy if the subject progressed on or within 6 months of adjuvant therapy administration.
b) In locally advanced and unresectable NSCLC, disease progression on or within 6 months of end of prior curatively intended multimodal therapy will count as a line of therapy. If chemoradiation is followed by planned systemic therapy without documented progression between chemoradiation and systemic therapy, the entire treatment course counts as one line of therapy.
• Subjects must have archived tumor tissue samples (formalin fixed, paraffin embedded [FFPE] sample [FFPE of excisional, core needle, or fine needle aspirates] collected within 5 years) or be willing to undergo pre-treatment tumor biopsy (excisional, core needle, or fine needle aspirates) prior to enrollment.
• Measurable disease per RECIST v1.1 criteria. Lesions previously radiated are not considered measurable unless they have progressed after radiation.
• ECOG Performance Status of ≤ 1
• Adequate hematologic laboratory assessments
• Life expectancy of > 3 months, in the opinion of the investigator
• Adequate liver function
• International normalized ratio (INR) and activated partial
thromboplastin time ≤ 1.5 x ULN
• Serum creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 60 mL/min.
Cockcroft-Gault formula will be used for creatinine clearance calculation.
Twenty-four hour urine collection is not required but is allowed.
• QTc ≤ 470 msec in females and ≤ 450 msec in males
• Ability to take oral medications and willing to record daily adherence
to investigational product

Critères de non-inclusion : • Subjects have received prior docetaxel in unresectable or metastatic setting.
• Mixed small-cell lung cancer and NSCLC histology
• Previously identified driver mutation (according to local standard of care or guidelines) other than KRAS p.G12C for which an approved therapy is available (including EGFR, ALK, etc).
• Active brain metastases. Subjects who have had brain metastases resected or have received whole brain radiation therapy ending at least 4 weeks (or stereotectic radiosurgery ending at least 2 weeks) prior to study day 1 are eligible if they meet all of the following criteria:
a) residual neurological symptoms grade ≤ 2;
b) on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and
c) follow-up MRI performed within 30 days prior to enrollment shows no progression or new lesions appearing.
• Leptomeningeal disease.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures at a frequency greater than monthly.
Subjects with PleurX catheters in place may be considered for the study with Medical Monitor approval.

Other Medical Conditions
• Known history of Human Immunodeficiency Virus (HIV) infection
• Exclusion of hepatitis infection based on the following results and/or
criteria:
a) Positive hepatitis B surface antigen (HepBsAg)
b) Negative HepBsAg with a positive for hepatitis B core antibody (Hepatitis B core antibody testing is not required for screening, however if this is done and is positive, then hepatitis B surface antibody [Anti-HBs] testing is necessary. Undetectable anti HBs in this setting would
suggest unclear and possible infection, and needs exclusion).
c) Positive Hepatitis C virus antibody: Hepatitis C virus RNA by polymerase chain reaction is necessary. Detectable Hepatitis C virus RNA renders the subject ineligible.
If above antibody/antigen testing is not able to be obtained, postive hepatitis B or C viral load
• Malignancy other than NSCLC within 3 years prior to randomization, with the exception of those with a negligible risk of metastases or death and treated with expected curative outcome.
• Major surgery within 28 days of study day 1
• Significant gastrointestinal disorder that results in significant malabsorption, requirement for intravenous alimentation, or inability to take oral medication.
• Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to study day 1, unstable arrhythmias or unstable angina.
• Severe infections within 4 weeks prior to randomization including, but not limited to hospitalization for complications of infection, bacteremia or severe pneumonia.
• Therapeutic oral or intravenous antibiotics within 2 weeks prior to randomization. Prophylactic antibiotics are allowed with Amgen medical monitor approval.
• Current CTCAE version 5.0 grade ≥ 2 peripheral neuropathy
Prior/Concomitant Therapy
• Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to CTCAE version 5.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (any grade allowed) or toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present and stable for > 6 months),
endocrine adverse events that are stably maintained on appropriate replacement therapy.
• Anti-tumor therapy within 4 weeks of study day 1; Please note that bisphosphonates or anti-Receptor Activator of Nuclear Factor Kappa Beta Ligand (anti RANKL) antibody therapy is allowed if needed for management of hypercalcemia or for prevention of skeletal events.
• Therapeutic or palliative radiation therapy within 2 weeks of study day 1. Subjects must have recovered from all radiotherapy related toxicity to CTCAE version 5.0 grade 1 or less with the exception of alopecia (any grade of alopecia allowed).
• Other investigational procedures are excluded
• Previous treatment with AMG 510 or other KRAS G12C inhibitor
• History of severe hypersensitivity to docetaxel or to other drugs formulated with polysorbate 80, or known sensitivity to any of the products or components to be administered during dosing.
• Use of known cytochrome P450 (CYP) 3A4 sensitive substrates (with a narrow therapeutic window), within 14 days or 5 half-lives of the drug
or its major active metabolite, whichever is longer, prior to study day 1 that was not reviewed and approved by the principal investigator and
the Amgen medical monitor.
• Use of strong inducers of CYP3A4 (including herbal supplements such as St. John's wort) within 14 days or 5 half-lives (whichever is longer)
prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor.
• Use of warfarin. Other anticoagulation may be allowed withAmgen
medical monitor approval
NCT
Promoteur
Coordonnateur
Informations relatives au promoteur
NCT :
NCT04303780
Promoteur :
AMGEN
Type de sponsor : Industriel
Arcs de Seine 18-20 Quai du Point du Jour
92100 BOULOGNE BILLANCOURT

Coordonnateur :
Centre investigateur
Investigateur
TEC / ARC / IDE
État
MÀJ
Informations relatives aux investigateurs
Centre investigateur :
Centre Hospitalier Universitaire de Lille - 2 Avenue Oscar Lambret - 59000 LILLE

Investigateur :
Professeur Alexis Cortot

TEC / ARC / IDE :
Eric Wasielewski
eric.wasielewski@
chru-lille.fr
03.20.44.56.12

Statut de l'essai : CLOS

MAJ : 15/04/2021