Clinical Trials List
Protocol NumberM15-819
NCT Number(ClinicalTrials.gov Identfier)NCT02955251
2018-07-24 - 2021-01-05
Phase I
Terminated1
ICD-9199.0
Disseminated malignant neoplasm
A Multi-Center, Phase 1, Open-Label, Dose-Escalation Study of ABBV-428, an Immunotherapy in Subjects With Advanced Solid Tumors
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Trial Applicant
AbbVie
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Sponsor
AbbVie
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Audit
None
Co-Principal Investigator
- CHAO-CHI HO CHAO-CHI HO Division of Thoracic Medicine
- 廖斌志 Division of Hematology & Oncology
- 吳尚俊 Division of General Internal Medicine
- Chong-Jen Yu Division of Thoracic Medicine
- Jih-Hsiang Lee Division of Hematology & Oncology
- 蔡子修 Division of General Internal Medicine
- James Chih-Hsin Yang Division of Hematology & Oncology
- 廖唯昱 Division of Thoracic Medicine
- 許嘉林 Division of General Internal Medicine
- Wen-Fang Cheng Division of General Internal Medicine
- JIN-YUAN SHIH Division of Thoracic Medicine
- 徐偉勛 醫學研究部
- 楊景堯 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Advanced Solid Tumors
Objectives
Primary:
● Evaluate the safety and tolerability of ABBV-428 when administered as
monotherapy or in combination with nivolumab
● Evaluate the PK of ABBV-428 when administered as monotherapy or in
combination with nivolumab
● Determine the maximum tolerated dose (MTD) and recommended Phase 2
dose (RPTD) for ABBV-428 when administered as monotherapy or in
combination with nivolumab
Secondary:
● Evaluate the preliminary efficacy of ABBV-428 when administered as
monotherapy or in combination with nivolumab
Test Drug
ABBV-428
Active Ingredient
ABBV-428
Dosage Form
injection
Dosage
24mg
Endpoints
Primary Outcome Measures :
Number of participants with adverse events [ Time Frame: First dose of study drug through at least 100 days after end of treatment; up to 2 years after last participants first dose ]
Recommended Phase 2 Dose (RPTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab [ Time Frame: 1 day of study drug administration within the 28-day cycle at the designated cohort dose ]
If a maximum tolerated dose (MTD) is reached, the RPTD of ABBV-428 will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and pharmacokinetic data.
Area under the serum concentration-time curve (AUC) of ABBV-428 [ Time Frame: Up to 30 days after a 24-month treatment period ]
Terminal half-life (t1/2) of ABBV-428 [ Time Frame: Up to 30 days after a 24-month treatment period ]
Maximum observed serum concentration (Cmax) of ABBV-428 [ Time Frame: Up to 30 days after a 24-month treatment period ]
Maximum tolerated dose (MTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab [ Time Frame: Up to 2 years ]
The highest dose level at which less than 2 of 6 participants or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.
Time to Cmax (Tmax) of ABBV-428 [ Time Frame: Up to 30 days after a 24-month treatment period ]
Number of participants with adverse events [ Time Frame: First dose of study drug through at least 100 days after end of treatment; up to 2 years after last participants first dose ]
Recommended Phase 2 Dose (RPTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab [ Time Frame: 1 day of study drug administration within the 28-day cycle at the designated cohort dose ]
If a maximum tolerated dose (MTD) is reached, the RPTD of ABBV-428 will not be a dose higher than the defined MTD, and will be selected based on the type(s) and occurrence(s) of dose limiting toxicities which occur in addition to the MTD. If a MTD is not reached, then the RPTD will be defined based on the safety and pharmacokinetic data.
Area under the serum concentration-time curve (AUC) of ABBV-428 [ Time Frame: Up to 30 days after a 24-month treatment period ]
Terminal half-life (t1/2) of ABBV-428 [ Time Frame: Up to 30 days after a 24-month treatment period ]
Maximum observed serum concentration (Cmax) of ABBV-428 [ Time Frame: Up to 30 days after a 24-month treatment period ]
Maximum tolerated dose (MTD) of ABBV-428 when administered as monotherapy or in combination with nivolumab [ Time Frame: Up to 2 years ]
The highest dose level at which less than 2 of 6 participants or less than 33% of (if cohort is expanded beyond 6) participants experience a dose limiting toxicity.
Time to Cmax (Tmax) of ABBV-428 [ Time Frame: Up to 30 days after a 24-month treatment period ]
Inclution Criteria
Inclusion Criteria
Inclusion Criteria for subjects in all study arms:
1. Subject must be ≥ 18 years of age.
2. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status
of 0 to 2.
3. All subjects must consent to provide archived diagnostic FFPE tumor tissue, if
available. If archived FFPE tumor tissue is not available or is of insufficient
quantity or quality, then a pretreatment fresh tumor biopsy will be required. The
pretreatment fresh tumor biopsy requirement may be waived at the discretion of the
Sponsor.
4. Subject is capable of understanding and complying with parameters as outlined in
the protocol and able to sign informed consent, approved by an Independent Ethics
Committee (IEC)/Institutional Review Board (IRB) prior to the initiation of any
screening or study-specific procedures.
5. Subject must have adequate bone marrow function without any growth factors or
transfusions within 2 weeks prior to the first dose, and is defined as: absolute
neutrophil count (ANC) ≥ 1,500/mm3
; platelets ≥ 100,000/mm3
; hemoglobin
≥ 9.0 g/dL.
6. Subject must have creatinine clearance ≥ 50 mL/min as measured by 24-hour urine
or estimated by the Cockcroft-Gault formula.
7. Subject must have total bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
8. Subjects with history of chronic heart failure must have echocardiogram (ECHO)
or multigated acquisition scan (MUGA) indicating left ventricular ejection fraction
(LVEF) ≥ 45% within 28 days prior to first dose of study drug.
9. A negative serum pregnancy test for all female subjects (except post-menopausal)
at the Screening Visit and a negative urine pregnancy test for all female subjects
(except post-menopausal) at baseline prior to the first dose of study drug.
10. If female, subject must be either postmenopausal, OR permanently surgically
sterile OR for women of childbearing potential practicing at least 1 protocolspecified method of birth control, that is effective from Cycle 1 Day 1 through at
least 3 or 5 months (monotherapy and combination therapy participants,
respectively) after the last dose of study drug.
11. If male, and subject is sexually active with female partner(s) of childbearing
potential, he must agree, from Cycle 1 Day 1 through at least 3 or 5 months
(monotherapy and combination therapy participants, respectively) after the last
dose of study drug, to practice the protocol-specified contraception.
12. Female who is not pregnant, breastfeeding, or considering becoming pregnant
during the study or for approximately at least 3 or 5 months (monotherapy and
combination therapy participants, respectively) after the last dose of study drug.
13. Male who is not considering fathering a child or donating sperm during the
study or for approximately at least 3 or 5 months (monotherapy and combination
therapy participants, respectively) after the last dose of study drug.
14. Measurable Disease: For all Dose–Expansion Arms, subjects must have
measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
Version 1.1 (RECIST v1.1).
● Subjects undergoing fresh tumor biopsies must have nontarget lesions that can
be biopsied at acceptable risk as judged by the investigator or if no nontarget
lesions suitable for biopsy, then a RECIST target lesion used for biopsy must
be ≥ 2 cm in longest diameter.
Inclusion Criteria for subjects in all study arms:
1. Subject must be ≥ 18 years of age.
2. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status
of 0 to 2.
3. All subjects must consent to provide archived diagnostic FFPE tumor tissue, if
available. If archived FFPE tumor tissue is not available or is of insufficient
quantity or quality, then a pretreatment fresh tumor biopsy will be required. The
pretreatment fresh tumor biopsy requirement may be waived at the discretion of the
Sponsor.
4. Subject is capable of understanding and complying with parameters as outlined in
the protocol and able to sign informed consent, approved by an Independent Ethics
Committee (IEC)/Institutional Review Board (IRB) prior to the initiation of any
screening or study-specific procedures.
5. Subject must have adequate bone marrow function without any growth factors or
transfusions within 2 weeks prior to the first dose, and is defined as: absolute
neutrophil count (ANC) ≥ 1,500/mm3
; platelets ≥ 100,000/mm3
; hemoglobin
≥ 9.0 g/dL.
6. Subject must have creatinine clearance ≥ 50 mL/min as measured by 24-hour urine
or estimated by the Cockcroft-Gault formula.
7. Subject must have total bilirubin ≤ 1.5 × ULN, aspartate aminotransferase (AST)
and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
8. Subjects with history of chronic heart failure must have echocardiogram (ECHO)
or multigated acquisition scan (MUGA) indicating left ventricular ejection fraction
(LVEF) ≥ 45% within 28 days prior to first dose of study drug.
9. A negative serum pregnancy test for all female subjects (except post-menopausal)
at the Screening Visit and a negative urine pregnancy test for all female subjects
(except post-menopausal) at baseline prior to the first dose of study drug.
10. If female, subject must be either postmenopausal, OR permanently surgically
sterile OR for women of childbearing potential practicing at least 1 protocolspecified method of birth control, that is effective from Cycle 1 Day 1 through at
least 3 or 5 months (monotherapy and combination therapy participants,
respectively) after the last dose of study drug.
11. If male, and subject is sexually active with female partner(s) of childbearing
potential, he must agree, from Cycle 1 Day 1 through at least 3 or 5 months
(monotherapy and combination therapy participants, respectively) after the last
dose of study drug, to practice the protocol-specified contraception.
12. Female who is not pregnant, breastfeeding, or considering becoming pregnant
during the study or for approximately at least 3 or 5 months (monotherapy and
combination therapy participants, respectively) after the last dose of study drug.
13. Male who is not considering fathering a child or donating sperm during the
study or for approximately at least 3 or 5 months (monotherapy and combination
therapy participants, respectively) after the last dose of study drug.
14. Measurable Disease: For all Dose–Expansion Arms, subjects must have
measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST)
Version 1.1 (RECIST v1.1).
● Subjects undergoing fresh tumor biopsies must have nontarget lesions that can
be biopsied at acceptable risk as judged by the investigator or if no nontarget
lesions suitable for biopsy, then a RECIST target lesion used for biopsy must
be ≥ 2 cm in longest diameter.
Exclusion Criteria
Exclusion Criteria
A subject will not be eligible for study participation if he/she meets any of the following
criteria:
1. Active or prior documented autoimmune disease (including, but not limited to,
inflammatory bowel disease, celiac disease, Wegener syndrome) within the past
2 years. Subjects with childhood atopy or asthma, vitiligo, alopecia, Hashimoto
syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the
past 2 years) are not excluded.
2. Current or prior use of immunosuppressive medication within 14 days prior to the
first dose of the study drug. The following are exceptions to this criterion:
● Intranasal, inhaled, topical steroids or local steroid injections (e.g., intra
articular injection).
● Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or equivalent.
● Steroids as premedication for hypersensitivity reactions (e.g., computed
tomography [CT] scan premedication).
3. History of primary immunodeficiency, bone marrow transplantation, chronic
lymphocytic leukemia, solid organ transplantation, or previous clinical diagnosis of
tuberculosis.
4. History of a coagulopathy or a platelet disorder.
5. Confirmed positive test results for human immunodeficiency virus (HIV), or
subjects with chronic or active hepatitis B or C. Subjects who have a history of hepatitis B or C who have documented cures after anti-viral therapy may be
enrolled.
6. Prior grade ≥ 3 immune-mediated neurotoxicity or pneumonitis while receiving
immunotherapy (including but not limited to agents directed against CTLA-4,
PD-L1, or PD 1). In addition, any other prior grade ≥ 3 immune-mediated adverse
event while receiving immunotherapy that has not resolved or become
asymptomatic within 3 months.
7. Known allergy or hypersensitivity to components of the study drug formulation.
8. Receipt of live, attenuated vaccine within 28 days prior to the first dose of the
study drug.
9. Receipt of anticancer therapy including chemotherapy, immunotherapy, radiation
therapy, biologic, herbal therapy, or any investigational therapy within a period of
21 days prior to the first dose of the study drug.
● Palliative radiation therapy for painful bone or skin metastasis is not subject to
a washout period.
10. Known uncontrolled metastases to the central nervous system (CNS).
● Subjects with brain metastases are eligible provided they have shown clinical
and radiographic stable disease for at least 4 weeks after definitive therapy and
have not used steroids for at least 4 weeks prior to first dose of the study drug.
11. Unresolved adverse events ≥ grade 2 National Cancer Institute Common
Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) from
prior anticancer therapy except for alopecia. Subjects with irreversible toxicity that
is not reasonably expected to be exacerbated by any of the investigational products
may be included (e.g., hearing loss) after consultation with the Medical Monitor.
12. History of major immunologic reaction to any IgG-containing agent.
13. Any medical condition which in the opinion of the Investigator places the subject at
an unacceptably high risk for toxicities.
14. Any medical condition which in the opinion of the Investigator would interfere
with evaluation of the investigational product or interpretation of subject safety or
study results (e.g., irritable bowel syndrome, radiation pneumonitis, etc.).
15. Female subject who is pregnant, breastfeeding or is considering becoming pregnant
during the study or for approximately 3 months after the last dose of study drug.
A subject will not be eligible for study participation if he/she meets any of the following
criteria:
1. Active or prior documented autoimmune disease (including, but not limited to,
inflammatory bowel disease, celiac disease, Wegener syndrome) within the past
2 years. Subjects with childhood atopy or asthma, vitiligo, alopecia, Hashimoto
syndrome, Grave's disease, or psoriasis not requiring systemic treatment (within the
past 2 years) are not excluded.
2. Current or prior use of immunosuppressive medication within 14 days prior to the
first dose of the study drug. The following are exceptions to this criterion:
● Intranasal, inhaled, topical steroids or local steroid injections (e.g., intra
articular injection).
● Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
prednisone or equivalent.
● Steroids as premedication for hypersensitivity reactions (e.g., computed
tomography [CT] scan premedication).
3. History of primary immunodeficiency, bone marrow transplantation, chronic
lymphocytic leukemia, solid organ transplantation, or previous clinical diagnosis of
tuberculosis.
4. History of a coagulopathy or a platelet disorder.
5. Confirmed positive test results for human immunodeficiency virus (HIV), or
subjects with chronic or active hepatitis B or C. Subjects who have a history of hepatitis B or C who have documented cures after anti-viral therapy may be
enrolled.
6. Prior grade ≥ 3 immune-mediated neurotoxicity or pneumonitis while receiving
immunotherapy (including but not limited to agents directed against CTLA-4,
PD-L1, or PD 1). In addition, any other prior grade ≥ 3 immune-mediated adverse
event while receiving immunotherapy that has not resolved or become
asymptomatic within 3 months.
7. Known allergy or hypersensitivity to components of the study drug formulation.
8. Receipt of live, attenuated vaccine within 28 days prior to the first dose of the
study drug.
9. Receipt of anticancer therapy including chemotherapy, immunotherapy, radiation
therapy, biologic, herbal therapy, or any investigational therapy within a period of
21 days prior to the first dose of the study drug.
● Palliative radiation therapy for painful bone or skin metastasis is not subject to
a washout period.
10. Known uncontrolled metastases to the central nervous system (CNS).
● Subjects with brain metastases are eligible provided they have shown clinical
and radiographic stable disease for at least 4 weeks after definitive therapy and
have not used steroids for at least 4 weeks prior to first dose of the study drug.
11. Unresolved adverse events ≥ grade 2 National Cancer Institute Common
Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) from
prior anticancer therapy except for alopecia. Subjects with irreversible toxicity that
is not reasonably expected to be exacerbated by any of the investigational products
may be included (e.g., hearing loss) after consultation with the Medical Monitor.
12. History of major immunologic reaction to any IgG-containing agent.
13. Any medical condition which in the opinion of the Investigator places the subject at
an unacceptably high risk for toxicities.
14. Any medical condition which in the opinion of the Investigator would interfere
with evaluation of the investigational product or interpretation of subject safety or
study results (e.g., irritable bowel syndrome, radiation pneumonitis, etc.).
15. Female subject who is pregnant, breastfeeding or is considering becoming pregnant
during the study or for approximately 3 months after the last dose of study drug.
The Estimated Number of Participants
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Taiwan
10 participants
-
Global
172 participants
