Clinical Trials List
Protocol Number20190009
NCT Number(ClinicalTrials.gov Identfier)NCT04303780
2020-06-01 - 2022-02-09
Phase III
Recruiting4
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
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
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Amgen Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Wei-Pang Chung Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
- Po-Lan Su Division of Thoracic Medicine
- Wen-Pin Su Division of Hematology & Oncology
- Chien-Chung Lin Division of Thoracic Medicine
- Shang-Yin Wu Division of Hematology & Oncology
- Chun-Hui Lee Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- YEN-HSIANG HUANG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jih-Hsiang Lee Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- 許嘉林 Division of General Internal Medicine
- YEN-TING LIN Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- 徐偉勛 Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- 楊景堯 Division of General Internal Medicine
- 廖斌志 Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
- 林宗哲 Division of Hematology & Oncology
- Chong-Jen Yu Division of General Internal Medicine
- 廖唯昱 Division of General Internal Medicine
- 吳尚俊 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yu-Chao Lin Division of Thoracic Medicine
- Chih-Yen Tu Division of Thoracic Medicine
- Chia-Hsiang Li Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Previously Treated Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated KRAS p.G12C
Objectives
Primary
• 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 non-small cell lung cancer (NSCLC)
Key Secondary
• 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)
Test Drug
AMG 510
Active Ingredient
AMG 510
Dosage Form
tablet
Dosage
120
Endpoints
Primary Outcome Measures :
Progression-free survival (PFS) [ Time Frame: Baseline to approximately 6 years ]
Defined as time from randomization until disease progression or death from any cause, whichever occurs first
Secondary Outcome Measures :
Overall Survival (OS) [ Time Frame: Baseline to approximately 6 years ]
Defined as time from randomization to death by any cause
Objective Response Rate (ORR) [ Time Frame: Baseline to approximately 6 years ]
Defined as complete response (CR ) + partial response (PR)
Patient Reported Outcomes (PRO) [ Time Frame: Baseline to week 12 ]
To be assessed by Patient-reported symptoms from selected PRO-Common Terminology Criteria for Adverse Events questions and GP5 of Functional Assessment of Cancer Therapy Tool General form (FACT-G)
Quality of Life Assessment [ Time Frame: Baseline to week 12 ]
To be 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)
Duration of response (DOR) [ Time Frame: Baseline to approximately 6 years ]
Defined as time from first evidence of PR or CR to disease progression or death due to any cause, whichever occurs first.
Time to response (TTR) [ Time Frame: Baseline to approximately 6 years ]
Defined as time from randomization to first evidence of PR or CR
Disease control rate (DCR) [ Time Frame: Baseline to approximately 6 years ]
Defined as rate of confirmed objective response (CR or PR) + stable disease (SD) per Response Evaluation Criteria in Solid Tumors version (RECIST) v1.1 of at least 6 weeks
Number of subjects with Clinically significant changes in vital signs [ Time Frame: Approximately 1 year ]
Number of subjects with treatment-emergent adverse events [ Time Frame: Estimated up to approximately 6 years ]
Number of subjects with Clinically significant changes in Laboratory tests [ Time Frame: Estimated up to approximately 1 year ]
Number of Subjects with treatment-related adverse events [ Time Frame: Estimated up to 6 years ]
Maximum plasma concentration (Cmax) [ Time Frame: Estimated up to 4 months ]
To characterize the pharmacokinetics (PK) of AMG 510
Area under the plasma concentration-time curve (AUC) [ Time Frame: Estimated up to 4 months ]
To characterize the pharmacokinetics (PK) of AMG 510
Progression-free survival (PFS) [ Time Frame: Baseline to approximately 6 years ]
Defined as time from randomization until disease progression or death from any cause, whichever occurs first
Secondary Outcome Measures :
Overall Survival (OS) [ Time Frame: Baseline to approximately 6 years ]
Defined as time from randomization to death by any cause
Objective Response Rate (ORR) [ Time Frame: Baseline to approximately 6 years ]
Defined as complete response (CR ) + partial response (PR)
Patient Reported Outcomes (PRO) [ Time Frame: Baseline to week 12 ]
To be assessed by Patient-reported symptoms from selected PRO-Common Terminology Criteria for Adverse Events questions and GP5 of Functional Assessment of Cancer Therapy Tool General form (FACT-G)
Quality of Life Assessment [ Time Frame: Baseline to week 12 ]
To be 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)
Duration of response (DOR) [ Time Frame: Baseline to approximately 6 years ]
Defined as time from first evidence of PR or CR to disease progression or death due to any cause, whichever occurs first.
Time to response (TTR) [ Time Frame: Baseline to approximately 6 years ]
Defined as time from randomization to first evidence of PR or CR
Disease control rate (DCR) [ Time Frame: Baseline to approximately 6 years ]
Defined as rate of confirmed objective response (CR or PR) + stable disease (SD) per Response Evaluation Criteria in Solid Tumors version (RECIST) v1.1 of at least 6 weeks
Number of subjects with Clinically significant changes in vital signs [ Time Frame: Approximately 1 year ]
Number of subjects with treatment-emergent adverse events [ Time Frame: Estimated up to approximately 6 years ]
Number of subjects with Clinically significant changes in Laboratory tests [ Time Frame: Estimated up to approximately 1 year ]
Number of Subjects with treatment-related adverse events [ Time Frame: Estimated up to 6 years ]
Maximum plasma concentration (Cmax) [ Time Frame: Estimated up to 4 months ]
To characterize the pharmacokinetics (PK) of AMG 510
Area under the plasma concentration-time curve (AUC) [ Time Frame: Estimated up to 4 months ]
To characterize the pharmacokinetics (PK) of AMG 510
Inclution Criteria
Inclusion Criteria
Subjects are eligible to be included in the study only if all of the following criteria apply:
101. Subject or subject’s legally acceptable representative has provided
informed consent prior to initiation of any study specific
activities/procedures.
102. Age ≥ 18 years of age
103. Histologically or pathologically documented, locally-advanced and
unresectable or metastatic NSCLC.
104. Have documentation of KRAS p.G12C mutation confirmed by central
testing through the current protocol or Amgen Study 20190294 prior to
enrollment.
105. 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.
c) Maintenance therapy following platinum doublet-based
chemotherapy is not considered as a separate line of
therapy.
106. 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.
107. Measurable disease per RECIST v1.1 criteria. Lesions previously
radiated are not considered measurable unless they have progressed
after radiation.
108. ECOG Performance Status of ≤ 1
109. Adequate hematologic laboratory assessments, defined as the following
within 10 days prior to start of study therapy:
a) Absolute neutrophil count (ANC) ≥ 1500 cells/µl (without
granulocyte colony-stimulating factor support within
10 days of laboratory test used to determine eligibility)
b) Hemoglobin ≥ 9.0 g/dL (without transfusion within
2 weeks of laboratory test used to determine eligibility)
c) Platelet count ≥ 100000/µl (without transfusion within
2 weeks of laboratory test used to determine eligibility)
110. Life expectancy of > 3 months, in the opinion of the investigator
111. Adequate liver function, defined as the following:
a) Aspartate aminotransferase (AST) and, alanine
aminotransferase (ALT) ≤ 2.5 times the upper limit of
normal (ULN), except if alkaline phosphatase
> 2.5 times the ULN, then AST and/or ALT must be
≤ 1.5 times the ULN
b) Serum bilirubin ≤ 1.0 x ULN
112. International normalized ratio (INR) and activated partial thromboplastin
time ≤ 1.5 x ULN
113. 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.
114. QTc ≤ 470 msec in females and ≤ 450 msec in males (based on
average of screening triplicates)
115. Ability to take oral medications and willing to record daily adherence to
investigational product
Subjects are eligible to be included in the study only if all of the following criteria apply:
101. Subject or subject’s legally acceptable representative has provided
informed consent prior to initiation of any study specific
activities/procedures.
102. Age ≥ 18 years of age
103. Histologically or pathologically documented, locally-advanced and
unresectable or metastatic NSCLC.
104. Have documentation of KRAS p.G12C mutation confirmed by central
testing through the current protocol or Amgen Study 20190294 prior to
enrollment.
105. 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.
c) Maintenance therapy following platinum doublet-based
chemotherapy is not considered as a separate line of
therapy.
106. 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.
107. Measurable disease per RECIST v1.1 criteria. Lesions previously
radiated are not considered measurable unless they have progressed
after radiation.
108. ECOG Performance Status of ≤ 1
109. Adequate hematologic laboratory assessments, defined as the following
within 10 days prior to start of study therapy:
a) Absolute neutrophil count (ANC) ≥ 1500 cells/µl (without
granulocyte colony-stimulating factor support within
10 days of laboratory test used to determine eligibility)
b) Hemoglobin ≥ 9.0 g/dL (without transfusion within
2 weeks of laboratory test used to determine eligibility)
c) Platelet count ≥ 100000/µl (without transfusion within
2 weeks of laboratory test used to determine eligibility)
110. Life expectancy of > 3 months, in the opinion of the investigator
111. Adequate liver function, defined as the following:
a) Aspartate aminotransferase (AST) and, alanine
aminotransferase (ALT) ≤ 2.5 times the upper limit of
normal (ULN), except if alkaline phosphatase
> 2.5 times the ULN, then AST and/or ALT must be
≤ 1.5 times the ULN
b) Serum bilirubin ≤ 1.0 x ULN
112. International normalized ratio (INR) and activated partial thromboplastin
time ≤ 1.5 x ULN
113. 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.
114. QTc ≤ 470 msec in females and ≤ 450 msec in males (based on
average of screening triplicates)
115. Ability to take oral medications and willing to record daily adherence to
investigational product
Exclusion Criteria
Exclusion Criteria
Subjects are excluded from the study if any of the following criteria apply:
Disease Related
201. Subjects have received prior docetaxel in unresectable or
metastatic setting (including subjects who received prior
docetaxel in first line for metastatic disease, but not including
subjects who received prior docetaxel neoadjuvantly or
adjuvantly and did not progress within 6 months of end of
therapy).
202. Mixed small-cell lung cancer and NSCLC histology
203. Previously identified driver mutation other than KRAS p.G12C
for which an approved therapy is available (including EGFR,
ALK, etc).
204. Active brain metastases. Subjects who have had brain
metastases resected or have received radiation therapy ending
at least 4 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.
205. Leptomeningeal disease.
206. Uncontrolled pleural effusion, pericardial effusion, or ascites
requiring recurrent drainage procedures at a frequency greater
than monthly. Patients with PleurX catheters in place may be
considered for the study with Medical Monitor approval.
Other Medical Conditions
207. Known history of Human Immunodeficiency Virus (HIV)
infection
208. Exclusion of hepatitis infection based on the following results
and/or criteria:
a) Positive hepatitis B surface antigen (HepBsAg) (indicative of
chronic Hepatitis B or recent acute hepatitis B)
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.
209. 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 (such as adequately treated carcinoma in situ of the
cervix, basal cell carcinoma, cutaneous squamous cell
carcinoma, localized prostate cancer treated with curative
intent, or ductal carcinoma in situ treated surgically with
curative intent).
210. Major surgery within 28 days of study day 1
211. Significant gastrointestinal disorder that results in significant
malabsorption, requirement for intravenous alimentation, or
inability to take oral medication.
212. 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.
213. Severe infections within 4 weeks prior to randomization
including, but not limited to hospitalization for complications of
infection, bacteremia or severe pneumonia.
214. Therapeutic oral or intravenous antibiotics within 2 weeks prior
to randomization. Prophylactic antibiotics are allowed with
Amgen medical monitor approval.
215. Current CTCAE version 5.0 grade ≥ 2 peripheral neuropathy
Prior/Concomitant Therapy
216. 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.
217. Anti-tumor therapy (chemotherapy, antibody therapy, molecular
targeted therapy, retinoid therapy, hormonal therapy [except
for subjects with history of completely resected breast cancer
with no active disease for over 3 years on long term adjuvant
endocrine therapy], or investigational agent) within 4 weeks of
study day 1; Please note that bisphosphonates or antiReceptor 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.
218. 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).
219. Other investigational procedures are excluded
220. Previous treatment with AMG 510 or other KRAS G12C
inhibitor
221. 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.
222. Use of known cytochrome P450 (CYP) 3A4 and Multidrug and
Toxin Extrusion (MATE1) 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.
223. Use of strong inhibitors of CYP3A4 or P glycoproteins (P-gp)
(including herbal supplements such as Goldenseal) within 14
days or 5 half-lives (whichever is longer) or grapefruit juice or
grapefruit containing products within 7 days prior to study day 1
that was not reviewed and approved by the principal
investigator and the Amgen medical monitor.
224. 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.
225. Use of warfarin. Other anticoagulation may be allowed with
Amgen medical monitor approval
Prior/Concurrent Clinical Study Experience
226. Currently enrolled in another investigational device or drug
study, or less than 4 weeks since ending another
investigational device or drug(s), or receiving other
investigational agent(s)
Other Exclusions
227. Female subject is pregnant or breastfeeding or planning to
become pregnant or breastfeed during treatment and for an
additional 7 days after the last dose of AMG 510 or during
treatment with docetaxel.
228. Female subjects of childbearing potential unwilling to use 1
highly effective method of contraception during treatment and
for an additional 7 days after the last dose of AMG 510 or
during treatment with docetaxel.
229. Female subjects of childbearing potential with a positive
pregnancy test assessed at Screening or day 1 by a serum
pregnancy test and/or urine pregnancy test.
230. Male subjects with a female partner of childbearing potential
who are unwilling to practice sexual abstinence (refrain from
heterosexual intercourse) or use contraception during
treatment and for an additional 7 days (AMG 510) or 6 months
(docetaxel) after the last dose of investigational product.
231. Male subjects with a pregnant partner who are unwilling to
practice abstinence or use a condom during treatment and for
an additional 7 days (AMG 510) or 6 months (docetaxel) after
the last dose of investigational product.
232. Male subjects unwilling to abstain from donating sperm during
treatment and for an additional 7 days (AMG 510) or 6 months
(docetaxel) after the last dose of investigational product.
Refer to Section 11.5 for additional contraceptive information.
233. Subject likely to not be available to complete all
protocol-required study visits or procedures, and/or to comply
with all required study procedures (eg, Clinical Outcome
Assessments) to the best of the subject and investigator’s
knowledge.
234. History or evidence of any other clinically significant disorder,
condition or disease (with the exception of those outlined
above) 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,
or interpretation of results.
Subjects are excluded from the study if any of the following criteria apply:
Disease Related
201. Subjects have received prior docetaxel in unresectable or
metastatic setting (including subjects who received prior
docetaxel in first line for metastatic disease, but not including
subjects who received prior docetaxel neoadjuvantly or
adjuvantly and did not progress within 6 months of end of
therapy).
202. Mixed small-cell lung cancer and NSCLC histology
203. Previously identified driver mutation other than KRAS p.G12C
for which an approved therapy is available (including EGFR,
ALK, etc).
204. Active brain metastases. Subjects who have had brain
metastases resected or have received radiation therapy ending
at least 4 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.
205. Leptomeningeal disease.
206. Uncontrolled pleural effusion, pericardial effusion, or ascites
requiring recurrent drainage procedures at a frequency greater
than monthly. Patients with PleurX catheters in place may be
considered for the study with Medical Monitor approval.
Other Medical Conditions
207. Known history of Human Immunodeficiency Virus (HIV)
infection
208. Exclusion of hepatitis infection based on the following results
and/or criteria:
a) Positive hepatitis B surface antigen (HepBsAg) (indicative of
chronic Hepatitis B or recent acute hepatitis B)
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.
209. 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 (such as adequately treated carcinoma in situ of the
cervix, basal cell carcinoma, cutaneous squamous cell
carcinoma, localized prostate cancer treated with curative
intent, or ductal carcinoma in situ treated surgically with
curative intent).
210. Major surgery within 28 days of study day 1
211. Significant gastrointestinal disorder that results in significant
malabsorption, requirement for intravenous alimentation, or
inability to take oral medication.
212. 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.
213. Severe infections within 4 weeks prior to randomization
including, but not limited to hospitalization for complications of
infection, bacteremia or severe pneumonia.
214. Therapeutic oral or intravenous antibiotics within 2 weeks prior
to randomization. Prophylactic antibiotics are allowed with
Amgen medical monitor approval.
215. Current CTCAE version 5.0 grade ≥ 2 peripheral neuropathy
Prior/Concomitant Therapy
216. 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.
217. Anti-tumor therapy (chemotherapy, antibody therapy, molecular
targeted therapy, retinoid therapy, hormonal therapy [except
for subjects with history of completely resected breast cancer
with no active disease for over 3 years on long term adjuvant
endocrine therapy], or investigational agent) within 4 weeks of
study day 1; Please note that bisphosphonates or antiReceptor 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.
218. 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).
219. Other investigational procedures are excluded
220. Previous treatment with AMG 510 or other KRAS G12C
inhibitor
221. 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.
222. Use of known cytochrome P450 (CYP) 3A4 and Multidrug and
Toxin Extrusion (MATE1) 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.
223. Use of strong inhibitors of CYP3A4 or P glycoproteins (P-gp)
(including herbal supplements such as Goldenseal) within 14
days or 5 half-lives (whichever is longer) or grapefruit juice or
grapefruit containing products within 7 days prior to study day 1
that was not reviewed and approved by the principal
investigator and the Amgen medical monitor.
224. 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.
225. Use of warfarin. Other anticoagulation may be allowed with
Amgen medical monitor approval
Prior/Concurrent Clinical Study Experience
226. Currently enrolled in another investigational device or drug
study, or less than 4 weeks since ending another
investigational device or drug(s), or receiving other
investigational agent(s)
Other Exclusions
227. Female subject is pregnant or breastfeeding or planning to
become pregnant or breastfeed during treatment and for an
additional 7 days after the last dose of AMG 510 or during
treatment with docetaxel.
228. Female subjects of childbearing potential unwilling to use 1
highly effective method of contraception during treatment and
for an additional 7 days after the last dose of AMG 510 or
during treatment with docetaxel.
229. Female subjects of childbearing potential with a positive
pregnancy test assessed at Screening or day 1 by a serum
pregnancy test and/or urine pregnancy test.
230. Male subjects with a female partner of childbearing potential
who are unwilling to practice sexual abstinence (refrain from
heterosexual intercourse) or use contraception during
treatment and for an additional 7 days (AMG 510) or 6 months
(docetaxel) after the last dose of investigational product.
231. Male subjects with a pregnant partner who are unwilling to
practice abstinence or use a condom during treatment and for
an additional 7 days (AMG 510) or 6 months (docetaxel) after
the last dose of investigational product.
232. Male subjects unwilling to abstain from donating sperm during
treatment and for an additional 7 days (AMG 510) or 6 months
(docetaxel) after the last dose of investigational product.
Refer to Section 11.5 for additional contraceptive information.
233. Subject likely to not be available to complete all
protocol-required study visits or procedures, and/or to comply
with all required study procedures (eg, Clinical Outcome
Assessments) to the best of the subject and investigator’s
knowledge.
234. History or evidence of any other clinically significant disorder,
condition or disease (with the exception of those outlined
above) 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,
or interpretation of results.
The Estimated Number of Participants
-
Taiwan
6 participants
-
Global
650 participants
