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
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
• 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