Previously treated locally advanced and unresectable or metastatic nonsmall cell lung cancer (NSCLC) with KRAS p.G12C mutation MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Amgen, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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 have documentation of KRAS p.G12C mutation through 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 250 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 80
Exclusion criteria
Exclusion criteria: • Subjects have received prior docetaxel in unresectable or metastatic setting. • Mixed small-cell lung cancer or mixed 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 stereotactic 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, positive 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 bisph
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 Objective: •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;Primary end point(s): • PFS - defined as time from randomization until disease progression or death from any cause, whichever occurs first for all subjects.;Timepoint(s) of evaluation of this end point: The timing for the PA of PFS will be event driven. If PFS early success is achieved in the IA, the IA will serve the purpose of PA of PFS. The final analysis of the study will be done when the last subject completes LTFU. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall survival - defined as time from randomization until death from any cause. • Objective response (complete response [CR] + partial response [PR]), assessed per RECIST v1.1. Response will be assessed by BICR. • Change from baseline over time to week 12 in disease related symptoms of: o Dyspnea as measured by a 4 item dyspnea domain from QLQ-C30 and QLQ-LC13 o Cough as measured by QLQ-LC13 o Chest Pain as measured by QLQ-LC13 • Change from baseline over time to week 12 in o Physical functioning as measured by QLQ-C30 o Global health status as measured by QLQ-C30 • Duration of response - defined as time from first evidence of PR or CR to disease progression or death due to any cause, whichever occurs first.;Timepoint(s) of evaluation of this end point: The timing for the PA of PFS will be event driven. If PFS early success is achieved in the IA, the IA will serve the purpose of PA of PFS. The final analysis of the study will be done when the last subject completes LTFU. | — |
Countries
Australia, Belgium, Brazil, Canada, China, Denmark, Finland, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Russian Federation, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactMedical Information
Amgen GmbH
Outcome results
None listed