Clinical Trials List
Protocol Number20190131
NCT Number(ClinicalTrials.gov Identfier)NCT04293094
2021-05-07 - 2023-06-15
Phase I
Recruiting3
A Phase 1, Multicenter, Open-label, Dose-Exploration and Dose-Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 650 in Subjects With Advanced Solid Tumors
-
Trial Applicant
IQVIA RDS Taiwan Ltd.
-
Sponsor
Amgen
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Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Jiun-I Lai Division of Hematology & Oncology
- 姜乃榕 Division of Hematology & Oncology
- Chun-Yu Liu Division of Hematology & Oncology
- Chien-An Liu Division of Radiology
- Ta-Chung Chao Division of Hematology & Oncology
- Yee Chao Division of Hematology & Oncology
- Yi-Jen Chen Division of Obstetrics & Gynecology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 張端瑩 Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
- YEN-SHEN LU Division of Hematology & Oncology
- Wen-Fang Cheng Division of Obstetrics & Gynecology
- 林季宏 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chyong-Huey Lai Division of Obstetrics & Gynecology
- Shin-Cheh Chen Division of General Surgery
- 周旭桓 Division of General Surgery
- Hsien-Kun Chang Division of Hematology & Oncology
- Wen-Chi Shen Division of Hematology & Oncology
- Ting-Chang Chang Division of Obstetrics & Gynecology
- 沈士哲 Division of General Surgery
- Gigin Lin Division of Radiology
- 周宏學 Division of Obstetrics & Gynecology
- Huei-Jean Huang Division of Obstetrics & Gynecology
- 黃寬仁 Division of Obstetrics & Gynecology
- Chia-Hui Chu Division of General Surgery
- Mengting Peng Division of Hematology & Oncology
- Ming-Mo Hou Division of Hematology & Oncology
- 周宏學 Division of Obstetrics & Gynecology
- Wen-Ling Kuo Division of General Surgery
- 黃培青 Division of Radiology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Advanced Solid Tumors
Objectives
主要目標
評估 AMG 650 對成人受試者的安全性及耐受性，並決定最高耐受劑量 (MTD)及/或第 2 期建議劑量 (RP2D)
次要目標
依據晚期實體腫瘤反應評估標準 (修改版 RECIST) 1.1 準則，評估 AMG 650的初步抗腫瘤活性
描述 AMG 650 的 PK 特性
探索性目標
藉由血液及/或腫瘤檢體的免疫組織化學、生化及/或基因分析，探討 AMG 650對於可能生物標記的作用。
評估食物 (高脂飲食) 對 AMG 650 PK
的影響
Test Drug
AMG 650
Active Ingredient
AMG 650
Dosage Form
Tablet
Dosage
25 mg tablet, 100 mg tablet
Endpoints
Primary endpoint:
Safety: subject incidence of dose limiting toxicities (DLTs), treatment-emergent adverse events, serious adverse events, treatment related adverse events, and changes in vital signs, electrocardiogram (ECG)s, and
clinical laboratory tests
Secondary endpoint:
Objective response rate (ORR)
Duration of response (DOR)
Progression-free survival (PFS)
Clinical Benefit rate (CBR)
Time to response (TTR)
Time to progression (TTP)
Overall survival (OS)
PK parameters of AMG 650 including, but not limited to, maximum observed plasma concentration (Cmax), time to achieve Cmax (Tmax), and area under the plasma concentration-time curve (AUC) in a dosing interval.
Exploratory:
Qualitative assessments for cell-cycle dynamics
Gene mutations/chromosome alterations relevant to KIF and other cell-cycle and DNA-damage related
markers
Levels of protein/DNA/RNA expression
AMG 650 PK parameters in the fed state, including, but not limited to Cmax, Tmax and AUC
Safety: subject incidence of dose limiting toxicities (DLTs), treatment-emergent adverse events, serious adverse events, treatment related adverse events, and changes in vital signs, electrocardiogram (ECG)s, and
clinical laboratory tests
Secondary endpoint:
Objective response rate (ORR)
Duration of response (DOR)
Progression-free survival (PFS)
Clinical Benefit rate (CBR)
Time to response (TTR)
Time to progression (TTP)
Overall survival (OS)
PK parameters of AMG 650 including, but not limited to, maximum observed plasma concentration (Cmax), time to achieve Cmax (Tmax), and area under the plasma concentration-time curve (AUC) in a dosing interval.
Exploratory:
Qualitative assessments for cell-cycle dynamics
Gene mutations/chromosome alterations relevant to KIF and other cell-cycle and DNA-damage related
markers
Levels of protein/DNA/RNA expression
AMG 650 PK parameters in the fed state, including, but not limited to Cmax, Tmax and AUC
Inclution Criteria
Inclusion Criteria:
Male and female ≥ 18 years old
Triple Negative Breast Cancer participants only: Participant must have histologically or cytologically confirmed metastatic or locally recurrent estrogen receptor (ER)-negative (<1% by immunohistochemistry [IHC]), progesterone receptor (PR)-negative (<1% IHC) and human epidermal growth factor receptor 2 (Her2)-negative (either fluorescent in situ hybridisation [FISH] negative, 0 or 1+ by IHC, or IHC2+ and FISH negative per ASCO/CAP definition) breast cancer. Participant must be relapsed/refractory to at least one line of systemic chemotherapy in the metastatic setting (excluding neoadjuvant or adjuvant chemotherapies) or intolerant of existing therapy(ies) known to provide clinical benefit or have no other available treatment options. Prior exposure to an immune checkpoint inhibitor is allowed.
Platinum-Resistant High Grade Serous Ovarian Cancer, primary peritoneal cancer and/or fallopian-tube cancer participants only: Participant must have histologically or cytologically confirmed diagnosis of metastatic or unresectable high grade serous ovarian cancer, with platinum-resistance defined as progression during or within 6 months of a platinum-containing regimen, with no other treatment option available. Prior exposure to platinum-resistant recurrence therapy is allowed.
Serous Endometrial Cancer participants only (Dose Exploration only): Participant must have histologically or cytologically confirmed diagnosis of metastatic or recurrent serous endometrial cancer, and be relapsed/refractory to at least one line of systemic therapy in the metastatic/recurrent setting or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
Participants with advanced or metastatic solid tumor with TP53MUT (Dose Exploration only, as assessed by local testing) that is unresectable and relapsed/refractory to at least one line of systemic chemotherapy or intolerant.
TNBC participants only (Dose Expansion): Progressed on no more than 3 prior lines of systemic therapy for locally advanced or metastatic disease (not including adjuvant or neo-adjuvant). Systemic therapy with poly ADP ribose polymerase (PARP) inhibitor will be counted as one line of therapy.
HGSOC participants only (Dose Expansion): Progressed on no more than 5 prior lines of systemic therapy for locally advanced or metastatic disease (not including adjuvant or neo-adjuvant). Systemic therapy with (PARP) inhibitor will be counted as one line of therapy. Induction followed by maintenance will be counted as one line of therapy.
Male and female ≥ 18 years old
Triple Negative Breast Cancer participants only: Participant must have histologically or cytologically confirmed metastatic or locally recurrent estrogen receptor (ER)-negative (<1% by immunohistochemistry [IHC]), progesterone receptor (PR)-negative (<1% IHC) and human epidermal growth factor receptor 2 (Her2)-negative (either fluorescent in situ hybridisation [FISH] negative, 0 or 1+ by IHC, or IHC2+ and FISH negative per ASCO/CAP definition) breast cancer. Participant must be relapsed/refractory to at least one line of systemic chemotherapy in the metastatic setting (excluding neoadjuvant or adjuvant chemotherapies) or intolerant of existing therapy(ies) known to provide clinical benefit or have no other available treatment options. Prior exposure to an immune checkpoint inhibitor is allowed.
Platinum-Resistant High Grade Serous Ovarian Cancer, primary peritoneal cancer and/or fallopian-tube cancer participants only: Participant must have histologically or cytologically confirmed diagnosis of metastatic or unresectable high grade serous ovarian cancer, with platinum-resistance defined as progression during or within 6 months of a platinum-containing regimen, with no other treatment option available. Prior exposure to platinum-resistant recurrence therapy is allowed.
Serous Endometrial Cancer participants only (Dose Exploration only): Participant must have histologically or cytologically confirmed diagnosis of metastatic or recurrent serous endometrial cancer, and be relapsed/refractory to at least one line of systemic therapy in the metastatic/recurrent setting or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
Participants with advanced or metastatic solid tumor with TP53MUT (Dose Exploration only, as assessed by local testing) that is unresectable and relapsed/refractory to at least one line of systemic chemotherapy or intolerant.
TNBC participants only (Dose Expansion): Progressed on no more than 3 prior lines of systemic therapy for locally advanced or metastatic disease (not including adjuvant or neo-adjuvant). Systemic therapy with poly ADP ribose polymerase (PARP) inhibitor will be counted as one line of therapy.
HGSOC participants only (Dose Expansion): Progressed on no more than 5 prior lines of systemic therapy for locally advanced or metastatic disease (not including adjuvant or neo-adjuvant). Systemic therapy with (PARP) inhibitor will be counted as one line of therapy. Induction followed by maintenance will be counted as one line of therapy.
Exclusion Criteria
Subjects are excluded from the study if any of the following criteria apply:
Disease Related
201. 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, if applicable; and c) follow-up MRI
shows no new lesions appearing.
202. Primary CNS tumor, hematological malignancies or lymphoma
203. Uncontrolled pleural effusion(s), pericardial effusion, or ascites (If those are
controlled with recurrent drainage procedures, subjects will be eligible for
enrollment)
Other Medical Conditions
204. Myocardial infarction within 6 months of study day 1, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or cardiac
arrhythmia requiring medication.
205. Gastrointestinal (GI) tract disease causing the inability to take oral medication,
malabsorption syndrome, requirement for intravenous alimentation,
gastric/jejunal tube feeds, uncontrolled inflammatory GI disease (eg, Crohn’s
disease, ulcerative colitis).
206. History of bowel obstruction, abdominal fistula, gastrointestinal perforation or
intra-abdominal abscess within 6 months of study entry unless approved by the
principal investigator and the Amgen medical monitor.
207. Use of any herbal or prescription medications known to be strong inhibitors of
cytochrome P450 3A (CYP3A) enzymes or membrane transporters P-gp and
breast cancer resistance protein (BCRP) (including but not limited to clarithromycin, itraconazole, ketoconazole or grapefruit juice or grapefruit
containing products) or narrow therapeutic index drugs (such as digoxin or
warfarin) within 7 days before receiving the first dose of study treatment. Use of
any herbal or prescription medications known to be strong Inducers (including but
not limited to phenytoin, rifampin, St John’s Wort) of CYP3A enzymes or
membrane transporters P-gp and BCRP within 28 days before receiving the first
dose of study treatment.
208. Clinically significant active infection within 2 weeks of the first dose of AMG 650
(day 1).
209. Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic
Hepatitis B), positive Hepatitis total core antibody with negative HepBsAg
(suggestive of occult hepatitis B) or detectable Hepatitis C virus Ribonucleic acid
(RNA) by PCR (indicative of active Hepatitis C - screening is generally done by
Hepatitis C Antibody (HepCAb), followed by Hepatitis C virus RNA by PCR if
HepCAb is positive).
210. Known positive test for HIV unless approved by the principal investigator and the
Amgen medical monitor.
211. Unresolved toxicities from prior anti-tumor therapy, defined as not having
resolved to Common Terminology Criteria for Adverse Events (CTCAE) version
5.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of
alopecia (Grade 2 or 3 toxicities from prior anti-tumor therapy that are considered
irreversible - defined as having been present and stable for > 6 months, such as
ifosfamide-related proteinuria, may be allowed if they are not otherwise described
in the exclusion criteria AND there is agreement to allow by both the investigator
and sponsor).
212. History of other malignancy within the past 2 years, with the following exceptions:
Malignancy treated with curative intent and with no known active disease
present for ≥ 2 years before enrollment and felt to be at low risk for
recurrence by the treating physician.
Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease.
Adequately treated cervical carcinoma in situ without evidence of disease.
Adequately treated breast ductal carcinoma in situ without evidence of
disease.
Prostatic intraepithelial neoplasia without evidence of prostate cancer.
Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
situ.
213. Major surgery within 28 days of study day 1.
214. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy,
hormonal therapy or investigational agent) within 28 days (unless 5 times the
half-life is shorter than 28 days); concurrent use of hormone deprivation therapy
for hormone-refractory prostate cancer, bisphosphonate or denosumab for
skeletal related events per institution guideline is permitted.
Therapeutic radiation therapy within 4 weeks (or palliative radiation therapy
within 2 weeks) of study day 1.
216. History of QT prolongation or Torsades de Pointes
229. Use of any sensitive CYP1A2 prescription drugs (including, but not limited
to alosetron, duloxetine, ramelteon, tasimelteon, and tizanidine), or
sensitive CYP2C9 prescription drugs (including, but not limited to
tolbutamide or celecoxib) within 7 days before receiving the first dose of
study treatment.
Prior/Concurrent Clinical Study Experience
217. Currently receiving treatment in another investigational device or drug study
within 28 days (unless 5 times the half-life is shorter than 28 days) since ending
treatment on another investigational device or drug studies, or receiving other
investigational agent(s).
218. Other investigational procedures are excluded.
Other Exclusions
219. Female subjects of childbearing potential unwilling to use protocol specified
method of contraception (see Section 11.5) during treatment and for an
additional 45 days after the last dose of AMG 650.
220. Female subjects who are breastfeeding or who plan to breastfeed while on study
through 15 days after the last dose of AMG 650.
221. Female subjects planning to become pregnant while on study through 45 days
after the last dose of AMG 650.
222. Female subjects of childbearing potential with a positive pregnancy test
assessed at screening and on day 1 by a highly sensitive urine or serum
pregnancy test.
223. 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 105 days after the last dose
of AMG 650. Refer to Section 11.5 for additional contraceptive information.
224. Male subjects with a pregnant partner who are unwilling to practice abstinence or
use a condom during treatment and for an additional 105 days after the last dose
of AMG 650.
225. Male subjects unwilling to abstain from donating sperm during treatment and for
an additional 105 days after the last dose of AMG 650.
226. Subject has known sensitivity to any of the products or components to be
administered during dosing.
227. 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.
228. 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.
Disease Related
201. 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, if applicable; and c) follow-up MRI
shows no new lesions appearing.
202. Primary CNS tumor, hematological malignancies or lymphoma
203. Uncontrolled pleural effusion(s), pericardial effusion, or ascites (If those are
controlled with recurrent drainage procedures, subjects will be eligible for
enrollment)
Other Medical Conditions
204. Myocardial infarction within 6 months of study day 1, symptomatic congestive
heart failure (New York Heart Association > class II), unstable angina, or cardiac
arrhythmia requiring medication.
205. Gastrointestinal (GI) tract disease causing the inability to take oral medication,
malabsorption syndrome, requirement for intravenous alimentation,
gastric/jejunal tube feeds, uncontrolled inflammatory GI disease (eg, Crohn’s
disease, ulcerative colitis).
206. History of bowel obstruction, abdominal fistula, gastrointestinal perforation or
intra-abdominal abscess within 6 months of study entry unless approved by the
principal investigator and the Amgen medical monitor.
207. Use of any herbal or prescription medications known to be strong inhibitors of
cytochrome P450 3A (CYP3A) enzymes or membrane transporters P-gp and
breast cancer resistance protein (BCRP) (including but not limited to clarithromycin, itraconazole, ketoconazole or grapefruit juice or grapefruit
containing products) or narrow therapeutic index drugs (such as digoxin or
warfarin) within 7 days before receiving the first dose of study treatment. Use of
any herbal or prescription medications known to be strong Inducers (including but
not limited to phenytoin, rifampin, St John’s Wort) of CYP3A enzymes or
membrane transporters P-gp and BCRP within 28 days before receiving the first
dose of study treatment.
208. Clinically significant active infection within 2 weeks of the first dose of AMG 650
(day 1).
209. Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic
Hepatitis B), positive Hepatitis total core antibody with negative HepBsAg
(suggestive of occult hepatitis B) or detectable Hepatitis C virus Ribonucleic acid
(RNA) by PCR (indicative of active Hepatitis C - screening is generally done by
Hepatitis C Antibody (HepCAb), followed by Hepatitis C virus RNA by PCR if
HepCAb is positive).
210. Known positive test for HIV unless approved by the principal investigator and the
Amgen medical monitor.
211. Unresolved toxicities from prior anti-tumor therapy, defined as not having
resolved to Common Terminology Criteria for Adverse Events (CTCAE) version
5.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of
alopecia (Grade 2 or 3 toxicities from prior anti-tumor therapy that are considered
irreversible - defined as having been present and stable for > 6 months, such as
ifosfamide-related proteinuria, may be allowed if they are not otherwise described
in the exclusion criteria AND there is agreement to allow by both the investigator
and sponsor).
212. History of other malignancy within the past 2 years, with the following exceptions:
Malignancy treated with curative intent and with no known active disease
present for ≥ 2 years before enrollment and felt to be at low risk for
recurrence by the treating physician.
Adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease.
Adequately treated cervical carcinoma in situ without evidence of disease.
Adequately treated breast ductal carcinoma in situ without evidence of
disease.
Prostatic intraepithelial neoplasia without evidence of prostate cancer.
Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
situ.
213. Major surgery within 28 days of study day 1.
214. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy,
hormonal therapy or investigational agent) within 28 days (unless 5 times the
half-life is shorter than 28 days); concurrent use of hormone deprivation therapy
for hormone-refractory prostate cancer, bisphosphonate or denosumab for
skeletal related events per institution guideline is permitted.
Therapeutic radiation therapy within 4 weeks (or palliative radiation therapy
within 2 weeks) of study day 1.
216. History of QT prolongation or Torsades de Pointes
229. Use of any sensitive CYP1A2 prescription drugs (including, but not limited
to alosetron, duloxetine, ramelteon, tasimelteon, and tizanidine), or
sensitive CYP2C9 prescription drugs (including, but not limited to
tolbutamide or celecoxib) within 7 days before receiving the first dose of
study treatment.
Prior/Concurrent Clinical Study Experience
217. Currently receiving treatment in another investigational device or drug study
within 28 days (unless 5 times the half-life is shorter than 28 days) since ending
treatment on another investigational device or drug studies, or receiving other
investigational agent(s).
218. Other investigational procedures are excluded.
Other Exclusions
219. Female subjects of childbearing potential unwilling to use protocol specified
method of contraception (see Section 11.5) during treatment and for an
additional 45 days after the last dose of AMG 650.
220. Female subjects who are breastfeeding or who plan to breastfeed while on study
through 15 days after the last dose of AMG 650.
221. Female subjects planning to become pregnant while on study through 45 days
after the last dose of AMG 650.
222. Female subjects of childbearing potential with a positive pregnancy test
assessed at screening and on day 1 by a highly sensitive urine or serum
pregnancy test.
223. 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 105 days after the last dose
of AMG 650. Refer to Section 11.5 for additional contraceptive information.
224. Male subjects with a pregnant partner who are unwilling to practice abstinence or
use a condom during treatment and for an additional 105 days after the last dose
of AMG 650.
225. Male subjects unwilling to abstain from donating sperm during treatment and for
an additional 105 days after the last dose of AMG 650.
226. Subject has known sensitivity to any of the products or components to be
administered during dosing.
227. 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.
228. 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.
The Estimated Number of Participants
-
Taiwan
9 participants
-
Global
140 participants
