Clinical Trials List
Protocol NumberM12-375
2012-07-01 - 2015-07-31
Phase I
Terminated3
A Multicenter, Phase 1/1b Open-Label, Dose-Escalation Study of ABT-700, a Monoclonal Antibody, in Subjects with Advanced Solid Tumor
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Trial Applicant
AbbVie
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 陳冠宇 Division of General Internal Medicine
- James Chih-Hsin Yang Division of Hematology & Oncology
- Ann-Lii Cheng Division of Hematology & Oncology
- 廖唯昱 Division of General Internal Medicine
- Chih-Hung Hsu Division of Hematology & Oncology
- Kun-Huei Yeh Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- Jih-Hsiang Lee Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- 林育麟 Division of General Internal Medicine
- YEN-SHEN LU Division of Hematology & Oncology
- Chong-Jen Yu Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Yan-Shen Shan Division of General Surgery
- Wu-Chou Su Division of General Internal Medicine
- Shang-Yin Wu Division of General Internal Medicine
- Li-Tzong Chen 國衛院
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Chih-Yen Tu Division of Thoracic Medicine
- Su-Peng Yeh Division of Hematology & Oncology
- Yu-Chao Lin Division of Thoracic Medicine
- Yu-Min Liao Division of Hematology & Oncology
- 廖偉志 Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
- Li-Yuan Bai Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
1 Terminated
Condition/Disease
Advance solid tumor/non-small cell lung cancer/astric/gastroesophageal junction adenocarcinoma
Objectives
The primary objectives:
To evaluate the safety and tolerability of ABT-700 when administered as monotherapy and in combination with a. docetaxel or b. 5-fluoruracil, folinic acid, irinotecan and cetuximab (FOLFIRI/cetuximab) or c. erlotinib.
To evaluate the pharmacokinetics of ABT-700 when administered as monotherapy and in combination with docetaxel or FOLFIRI/cetuximab or erlotinib.
To determine the recommended Phase 2 dose (RPTD) for ABT-700 when administered as monotherapy and in combination with docetaxel or FOLFIRI/cetuximab or erlotinib.
Secondary:
To evaluate the preliminary efficacy of ABT-700 when administered as monotherapy and in
combination with docetaxel or FOLFIRI/cetuximab or erlotinib.
Test Drug
ABT-700
Active Ingredient
ABT-700
Dosage Form
Lyophilized Powder for Injection
Dosage
100
Endpoints
Efficacy:
The efficacy endpoints include objective response rate (ORR) (determined using RECIST version 1.1), progression free survival (PFS), and duration of overall response (DOR).
Pharmacokinetic:
Blood samples for assay of ABT-700 drug levels will be used to determine PK parameters. Blood samples for antidrug antibody (ADA) will be collected at designated time points throughout the study and ADA will be correlated with PK and safety outcomes.
Safety:
Adverse events, laboratory profiles, physical exams, and vital signs will be assessed throughout the study. Adverse events will be graded according the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
The efficacy endpoints include objective response rate (ORR) (determined using RECIST version 1.1), progression free survival (PFS), and duration of overall response (DOR).
Pharmacokinetic:
Blood samples for assay of ABT-700 drug levels will be used to determine PK parameters. Blood samples for antidrug antibody (ADA) will be collected at designated time points throughout the study and ADA will be correlated with PK and safety outcomes.
Safety:
Adverse events, laboratory profiles, physical exams, and vital signs will be assessed throughout the study. Adverse events will be graded according the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03.
Inclution Criteria
Inclusion for ABT-700 monotherapy dose-escalation/expansion:
Subject must be ≥ 18 years of age.
Subjects with advanced solid tumors.
Dose-escalation: likely to overexpress c-Met
Dose-expansion: evidence for MET gene amplification
Subject must have disease: a) that is not amenable to surgical resection, or b) that has progressed or recurred despite standard therapy, or c) that has failed to respond to standard therapy or d) for which no effective therapy exists.
Subject cannot tolerate or must not be eligible for other approved therapeutic options with known survival advantage.
Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
Subject must have measurable disease per RECIST version 1.1 (Appendix C) or disease evaluable by assessment of tumor antigens ≥ 2 × upper limit of normal (ULN).
Subject has one of the following tumor tissues confirmed available for analyses:
Archived diagnostic formalin-fixed paraffin embedded (FFPE)
Biopsy collected prior to study drug administration (FFPE).
Subject has adequate bone marrow, renal, and hepatic function as follows:
Bone marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3, Platelets ≥ 100,000/mm3 ; Hemoglobin ≥ 9.0 g/dL.
Renal function: Serum creatinine ≤ 1.5 × the Institution's ULN range or creatinine clearance ≥ 50 mL/min measured by 24-hour urine or estimated by the Cockcroft-Gault formula:
CrCl (mL/min) = (140 – age in years) × (weight in kg) (× 0.85 if female) / 72 × serum creatinine (mg/dL)
Hepatic function: Bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × the ULN and albumin ≥ 3.0 g/dL. Subjects with liver metastasis may have an AST and ALT of ≤ 5.0 × the ULN.
Women of childbearing potential must have a negative serum pregnancy test within
14 days prior to initiation of treatment. Subjects with initial positive serum pregnancy tests are eligible if it is determined through other means that the subject is not pregnant (i.e., ultrasound in cases where tumor is suspected of secreting β-HCG and resulting in a false-positive pregnancy test). Female subjects considered not of childbearing potential must be documented as being surgically sterile or post-menopausal for at least 1 year. Women of childbearing potential and men must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and for a period of 90 days after the last dose of study drug.
Vasectomy(a vasectomized male subject or a vasectomized partner of a female subject)
Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration.
Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream).
Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Institutional Review Board (IRB) prior to the initiation of any screening or study-specific procedures.
Additional inclusion criteria for subjects enrolled on the combination therapy phase:
Subject in the combination therapy cohorts must meet the above inclusion criteria and be eligible to receive docetaxel or FOLFIRI/cetuximab or erlotinib per most current prescribing information, or at the discretion of the Investigator.
The following indications and lines of prior cytotoxic therapy for metastatic disease:
Combination cohort A: ABT-700 plus docetaxel
- Subjects with NSCLC or AGEC who have had one prior line of cytotoxic therapy
Combination cohort B: ABT-700 plus FOLFIRI/cetuximab
- Subjects with CRC who have zero or one prior line of cytotoxic therapy
Combination cohort C: ABT-700 plus erlotinib
- Subjects with NSCLC who have had up to two prior lines of cytotoxic therapy
Subject must be ≥ 18 years of age.
Subjects with advanced solid tumors.
Dose-escalation: likely to overexpress c-Met
Dose-expansion: evidence for MET gene amplification
Subject must have disease: a) that is not amenable to surgical resection, or b) that has progressed or recurred despite standard therapy, or c) that has failed to respond to standard therapy or d) for which no effective therapy exists.
Subject cannot tolerate or must not be eligible for other approved therapeutic options with known survival advantage.
Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.
Subject must have measurable disease per RECIST version 1.1 (Appendix C) or disease evaluable by assessment of tumor antigens ≥ 2 × upper limit of normal (ULN).
Subject has one of the following tumor tissues confirmed available for analyses:
Archived diagnostic formalin-fixed paraffin embedded (FFPE)
Biopsy collected prior to study drug administration (FFPE).
Subject has adequate bone marrow, renal, and hepatic function as follows:
Bone marrow: Absolute neutrophil count (ANC) ≥ 1,500/mm3, Platelets ≥ 100,000/mm3 ; Hemoglobin ≥ 9.0 g/dL.
Renal function: Serum creatinine ≤ 1.5 × the Institution's ULN range or creatinine clearance ≥ 50 mL/min measured by 24-hour urine or estimated by the Cockcroft-Gault formula:
CrCl (mL/min) = (140 – age in years) × (weight in kg) (× 0.85 if female) / 72 × serum creatinine (mg/dL)
Hepatic function: Bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 × the ULN and albumin ≥ 3.0 g/dL. Subjects with liver metastasis may have an AST and ALT of ≤ 5.0 × the ULN.
Women of childbearing potential must have a negative serum pregnancy test within
14 days prior to initiation of treatment. Subjects with initial positive serum pregnancy tests are eligible if it is determined through other means that the subject is not pregnant (i.e., ultrasound in cases where tumor is suspected of secreting β-HCG and resulting in a false-positive pregnancy test). Female subjects considered not of childbearing potential must be documented as being surgically sterile or post-menopausal for at least 1 year. Women of childbearing potential and men must agree to use adequate contraception (one of the following listed below) prior to study entry, for the duration of study participation and for a period of 90 days after the last dose of study drug.
Vasectomy(a vasectomized male subject or a vasectomized partner of a female subject)
Hormonal contraceptives (oral, parenteral or transdermal) for at least 3 months prior to study drug administration.
Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream).
Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent, approved by an Institutional Review Board (IRB) prior to the initiation of any screening or study-specific procedures.
Additional inclusion criteria for subjects enrolled on the combination therapy phase:
Subject in the combination therapy cohorts must meet the above inclusion criteria and be eligible to receive docetaxel or FOLFIRI/cetuximab or erlotinib per most current prescribing information, or at the discretion of the Investigator.
The following indications and lines of prior cytotoxic therapy for metastatic disease:
Combination cohort A: ABT-700 plus docetaxel
- Subjects with NSCLC or AGEC who have had one prior line of cytotoxic therapy
Combination cohort B: ABT-700 plus FOLFIRI/cetuximab
- Subjects with CRC who have zero or one prior line of cytotoxic therapy
Combination cohort C: ABT-700 plus erlotinib
- Subjects with NSCLC who have had up to two prior lines of cytotoxic therapy
Exclusion Criteria
A subject will not be eligible for study participation if he/she meets any of the following
criteria:
For all cohorts:
Subject has received anticancer therapy including chemotherapy, radiation therapy,
immunotherapy, biologic, or any investigational therapy within a period of 21 days or herbal therapy within 7 days prior to the first dose of ABT-700.
o Palliative radiation therapy for painful bony or skin metastasis for 10 fractions or less is not subject to a washout period
Subject has known uncontrolled metastases to the central nervous system (CNS).
Subjects with brain metastases are eligible provided they have shown clinical and radiographic stable disease after definitive therapy and have not used steroids for at least 1 month prior to first dose of ABT-700.
Subject has unresolved adverse events > Grade 1 from prior anticancer therapy, except for alopecia or anemia.
Subject has had major surgery within 21 days prior to the first dose of ABT-700.
Subject has a clinically significant uncontrolled condition(s) including but not limited to the following:
o Grade ≥ 2 peripheral edema.
o Active uncontrolled infection.
o Symptomatic congestive heart failure.
o Unstable angina pectoris or cardiac arrhythmia.
o Psychiatric illness/social situation that would limit compliance with the study.
Subject has history of major immunologic reaction to any IgG containing agent.
Subject has any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities.
Subject is a lactating or pregnant female.
Subject with non-measureable/non-evaluable disease by RECIST v1.1 except for subjects with tumor antigens ≥ 2 × ULN.
Additional exclusion criteria for subjects enrolled on the combination therapy phase:
Subjects enrolled in the combination therapy phase must not meet the above exclusion
criteria and be eligible to receive docetaxel or FOLFIRI/cetuximab or erlotinib per most
current prescribing information, or at the discretion of the Investigator.
Subjects may not receive docetaxel if they have:
。 Pre-existing peripheral neuropathy Grade ≥ 2.
。 Received live vaccine(s) within 28 days prior to Cycle 1 Day 1.
。 Had a severe hypersensitivity reaction to any drug formulated in polysorbate 80.
。 Had prior docetaxel therapy.
。 Any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities from docetaxel.
Subject may not receive FOLFIRI/cetuximab if they have:
。 A history of hypersensitivity reaction to the drugs or their excipients.
。 Clinically active/symptomatic interstitial lung disease.
。 Dehydration (Grade > 1).
。 Diarrhea (Grade > 1).
。 Received live vaccine(s) within 28 days of Cycle 1 Day 1.
。 Kras mutation-positive tumor.
。 Any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities from FOLFIRI/cetuximab.
Subjects may not receive erlotinib if they have:
Any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities from erlotinib.
criteria:
For all cohorts:
Subject has received anticancer therapy including chemotherapy, radiation therapy,
immunotherapy, biologic, or any investigational therapy within a period of 21 days or herbal therapy within 7 days prior to the first dose of ABT-700.
o Palliative radiation therapy for painful bony or skin metastasis for 10 fractions or less is not subject to a washout period
Subject has known uncontrolled metastases to the central nervous system (CNS).
Subjects with brain metastases are eligible provided they have shown clinical and radiographic stable disease after definitive therapy and have not used steroids for at least 1 month prior to first dose of ABT-700.
Subject has unresolved adverse events > Grade 1 from prior anticancer therapy, except for alopecia or anemia.
Subject has had major surgery within 21 days prior to the first dose of ABT-700.
Subject has a clinically significant uncontrolled condition(s) including but not limited to the following:
o Grade ≥ 2 peripheral edema.
o Active uncontrolled infection.
o Symptomatic congestive heart failure.
o Unstable angina pectoris or cardiac arrhythmia.
o Psychiatric illness/social situation that would limit compliance with the study.
Subject has history of major immunologic reaction to any IgG containing agent.
Subject has any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities.
Subject is a lactating or pregnant female.
Subject with non-measureable/non-evaluable disease by RECIST v1.1 except for subjects with tumor antigens ≥ 2 × ULN.
Additional exclusion criteria for subjects enrolled on the combination therapy phase:
Subjects enrolled in the combination therapy phase must not meet the above exclusion
criteria and be eligible to receive docetaxel or FOLFIRI/cetuximab or erlotinib per most
current prescribing information, or at the discretion of the Investigator.
Subjects may not receive docetaxel if they have:
。 Pre-existing peripheral neuropathy Grade ≥ 2.
。 Received live vaccine(s) within 28 days prior to Cycle 1 Day 1.
。 Had a severe hypersensitivity reaction to any drug formulated in polysorbate 80.
。 Had prior docetaxel therapy.
。 Any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities from docetaxel.
Subject may not receive FOLFIRI/cetuximab if they have:
。 A history of hypersensitivity reaction to the drugs or their excipients.
。 Clinically active/symptomatic interstitial lung disease.
。 Dehydration (Grade > 1).
。 Diarrhea (Grade > 1).
。 Received live vaccine(s) within 28 days of Cycle 1 Day 1.
。 Kras mutation-positive tumor.
。 Any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities from FOLFIRI/cetuximab.
Subjects may not receive erlotinib if they have:
Any medical condition which in the opinion of the Investigator places the subject at an unacceptably high risk for toxicities from erlotinib.
The Estimated Number of Participants
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Taiwan
30 participants
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Global
124 participants
