Clinical Trials List
Protocol NumberM16-074
NCT Number(ClinicalTrials.gov Identfier)NCT03071757
2018-03-10 - 2021-06-30
Phase I
Terminated5
ICD-9199.0
Disseminated malignant neoplasm
A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of ABBV-368 as a Single Agent and Combination in Subjects With Locally Advanced or Metastatic 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
Co-Principal Investigator
- Wen-Pin Su Division of General Internal Medicine
- Jui-Hung Tsai Division of General Internal Medicine
- Yu-Min Yeh Division of General Internal Medicine
- Wei-Pang Chung Division of General Internal Medicine
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- 林季宏 Division of Hematology & Oncology
- 張端瑩 Division of Hematology & Oncology
- YEN-SHEN LU Division of Hematology & Oncology
- 陳怡君 Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- Wei-Wu Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
- 夏和雄 Division of Hematology & Oncology
- HSIN-TE HSU Division of Otolaryngology
- Huey-En Tzeng Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
1 Terminated
Audit
None
Co-Principal Investigator
- 張端瑩 Division of Hematology & Oncology
- 廖斌志 Division of Hematology & Oncology
- 陳怡君 Division of Hematology & Oncology
- 林季宏 Division of Hematology & Oncology
- YEN-SHEN LU Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Wen-Pin Su Division of General Internal Medicine
- Yu-Min Yeh Division of General Internal Medicine
- Jui-Hung Tsai Division of General Internal Medicine
- Wei-Pang Chung Division of General Internal Medicine
- Shang-Yin Wu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Condition/Disease
Locally Advanced or Metastatic Solid Tumors
Objectives
Objectives for Part 1 Dose Escalation
Primary Objectives:
To assess safety, tolerability and pharmacokinetics (PK) at increasing dose levels of single agent
ABBV-368 in patients with selected advanced or metastatic solid tumors in order to establish the
maximum tolerated dose (MTD) or reach the maximally administered dose (MAD)
To assess safety, tolerability and PK at increasing dose levels of ABBV-368 in combination with
nivolumab in advanced or metastatic solid tumors in order to establish the MTD or reach the
MAD
Objectives for Part 2, Cohort Expansion
Primary Objectives:
To further assess safety, tolerability, and PK of ABBV-368 given as a single agent and in
combination with nivolumab in patients with selected advanced or metastatic solid tumors in
order to establish the recommended Phase 2 dose (RPTD)
Test Drug
ABBV-368
Active Ingredient
ABBV-368
Dosage Form
injection
Dosage
50
Endpoints
Efficacy:
The efficacy endpoints include objective response rate (ORR), clinical benefit rate (CBR, defined as CR,
PR or SD), progression-free survival (PFS), and duration of overall response (DOR). Efficacy endpoints
will be assessed to both RECIST (v1.1) and irRECIST.
Pharmacokinetic:
Concentrations of ABBV-368 and ADA will be determined at designated time points throughout the
study. Values for the PK parameters of ABBV-368 including the maximum observed serum
concentration (Cmax), the time to Cmax (Tmax), the area under the serum concentration-time curve (AUC),
and terminal half-life (t1/2) will be determined using the non-compartmental methods. Additional
parameters will be determined if deemed useful and appropriate.
Pharmacodynamic:
Biomarkers:
Exploratory research will be conducted to study biomarker relationship with PK, safety and clinical
responses.
Safety:
Adverse events, laboratory profiles, physical exams, and vital signs will be assessed throughout the study.
Adverse events will be graded according the NCI CTCAE v.4.03.
The efficacy endpoints include objective response rate (ORR), clinical benefit rate (CBR, defined as CR,
PR or SD), progression-free survival (PFS), and duration of overall response (DOR). Efficacy endpoints
will be assessed to both RECIST (v1.1) and irRECIST.
Pharmacokinetic:
Concentrations of ABBV-368 and ADA will be determined at designated time points throughout the
study. Values for the PK parameters of ABBV-368 including the maximum observed serum
concentration (Cmax), the time to Cmax (Tmax), the area under the serum concentration-time curve (AUC),
and terminal half-life (t1/2) will be determined using the non-compartmental methods. Additional
parameters will be determined if deemed useful and appropriate.
Pharmacodynamic:
Biomarkers:
Exploratory research will be conducted to study biomarker relationship with PK, safety and clinical
responses.
Safety:
Adverse events, laboratory profiles, physical exams, and vital signs will be assessed throughout the study.
Adverse events will be graded according the NCI CTCAE v.4.03.
Inclution Criteria
Main Inclusion:
1. Subject must be ≥ 18 years of age.
2. Subject must have histologic or cytology diagnosis of a known immunogenic solid tumor, as outlined in inclusion criteria 3 and 4 below.
3. For Parts 1A and 1B: Subjects with advanced or metastatic solid tumors that have exhausted standard treatment for their incurable disease and who may be treatment naïve to a PD-1/PD-L1 targeting agent and for which there is no anti-PD-1/PD-L1 agent approved. Eligible tumor types include: triple negative breast cancer, ovarian cancer, HCC, gastric cancer, small cell lung cancer, mesothelioma, cholangiocarcinoma, Merkel cell carcinoma, and tumors with evidence of DNA mismatch repair deficiency. Additional tumor types such as first-line melanoma, second-line NSCLC, head and neck, bladder and renal cell carcinoma may be considered at the Sponsor's discretion provided such patients in Cohort 1A have failed prior PD-1/PD-L1 therapy, and patients in Cohort 1B are naïve to PD-1/PD-L1 targeting therapy.
4. For Part 2 cohort-expansion:
NSCLC cohort: Subjects with locally advanced or metastatic NSCLC who have failed platinum-based therapy and a PD-1/PD-L1 targeting agent. Patients with known genomic tumor aberrations for which there is approved targeted therapy (e.g., EGFR and ALK) should have disease progression on these therapies. Head and Neck cohort: Subjects with recurrent squamous cell head and neck carcinoma that are not candidates for curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies. Tumor progression or recurrence must have occurred within 6 months of last dose of platinum therapy in the adjuvant (i.e., with radiation after surgery), primary (i.e., with radiation), recurrent, or metastatic setting. Subjects must be treatment-naïve to a PD-1/PD-L1 targeting agent.
5. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
6. Subject must have irRECIST evaluable or measurable disease in the PART 1 and measurable disease per irRECIST in PART 2.
7. Subject has one of the following tumor tissues confirmed available for analyses:
-Archived diagnostic formalin-fixed paraffin embedded (FFPE), or
-Biopsy collected prior to study drug administration (FFPE).
8. Subject must have adequate bone marrow function defined as:
-absolute neutrophil count (ANC) ≥ 1,500/mm3 ;
-platelets ≥ 100,000/mm3 ;
-hemoglobin ≥ 9.0 g/dL.
9. Subject must have serum creatinine ≤ 1.5 mg/dL (or ≤ 3.0 mg/dL if related to underlying tumor).
10. Subject must have adequate liver function including:
-total bilirubin ≤ 1.5 × ULN unless the patient has documented Gilbert's syndrome;
-aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 × ULN. Subjects
with liver metastasis may have an AST and ALT of ≤ 5.0 × the ULN.
11. Subjects with history of chronic heart failure must have cardiac echocardiogram (ECHO) or multigated acquisition scan (MUGA) indicating left ventricular ejection fraction (LVEF) ≥ 45% within 21 days prior to first dose of study drug.
12. If female, subject must be either postmenopausal OR permanently surgically sterile OR for Women of Childbearing Potential practicing at least one protocol specified method of birth control (Section 5.2.4) prior to starting study at Cycle 1 Day 1 through at least 4 month after the last dose of study drug.
13. If the male subject is sexually active, he must agree, from Study Day 1 through at least 4 months after the last dose of study drug, to practice the protocol specified contraception (Section 5.2.4).
14. 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.
1. Subject must be ≥ 18 years of age.
2. Subject must have histologic or cytology diagnosis of a known immunogenic solid tumor, as outlined in inclusion criteria 3 and 4 below.
3. For Parts 1A and 1B: Subjects with advanced or metastatic solid tumors that have exhausted standard treatment for their incurable disease and who may be treatment naïve to a PD-1/PD-L1 targeting agent and for which there is no anti-PD-1/PD-L1 agent approved. Eligible tumor types include: triple negative breast cancer, ovarian cancer, HCC, gastric cancer, small cell lung cancer, mesothelioma, cholangiocarcinoma, Merkel cell carcinoma, and tumors with evidence of DNA mismatch repair deficiency. Additional tumor types such as first-line melanoma, second-line NSCLC, head and neck, bladder and renal cell carcinoma may be considered at the Sponsor's discretion provided such patients in Cohort 1A have failed prior PD-1/PD-L1 therapy, and patients in Cohort 1B are naïve to PD-1/PD-L1 targeting therapy.
4. For Part 2 cohort-expansion:
NSCLC cohort: Subjects with locally advanced or metastatic NSCLC who have failed platinum-based therapy and a PD-1/PD-L1 targeting agent. Patients with known genomic tumor aberrations for which there is approved targeted therapy (e.g., EGFR and ALK) should have disease progression on these therapies. Head and Neck cohort: Subjects with recurrent squamous cell head and neck carcinoma that are not candidates for curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies. Tumor progression or recurrence must have occurred within 6 months of last dose of platinum therapy in the adjuvant (i.e., with radiation after surgery), primary (i.e., with radiation), recurrent, or metastatic setting. Subjects must be treatment-naïve to a PD-1/PD-L1 targeting agent.
5. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2.
6. Subject must have irRECIST evaluable or measurable disease in the PART 1 and measurable disease per irRECIST in PART 2.
7. Subject has one of the following tumor tissues confirmed available for analyses:
-Archived diagnostic formalin-fixed paraffin embedded (FFPE), or
-Biopsy collected prior to study drug administration (FFPE).
8. Subject must have adequate bone marrow function defined as:
-absolute neutrophil count (ANC) ≥ 1,500/mm3 ;
-platelets ≥ 100,000/mm3 ;
-hemoglobin ≥ 9.0 g/dL.
9. Subject must have serum creatinine ≤ 1.5 mg/dL (or ≤ 3.0 mg/dL if related to underlying tumor).
10. Subject must have adequate liver function including:
-total bilirubin ≤ 1.5 × ULN unless the patient has documented Gilbert's syndrome;
-aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 × ULN. Subjects
with liver metastasis may have an AST and ALT of ≤ 5.0 × the ULN.
11. Subjects with history of chronic heart failure must have cardiac echocardiogram (ECHO) or multigated acquisition scan (MUGA) indicating left ventricular ejection fraction (LVEF) ≥ 45% within 21 days prior to first dose of study drug.
12. If female, subject must be either postmenopausal OR permanently surgically sterile OR for Women of Childbearing Potential practicing at least one protocol specified method of birth control (Section 5.2.4) prior to starting study at Cycle 1 Day 1 through at least 4 month after the last dose of study drug.
13. If the male subject is sexually active, he must agree, from Study Day 1 through at least 4 months after the last dose of study drug, to practice the protocol specified contraception (Section 5.2.4).
14. 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.
Exclusion Criteria
1. Subject has received 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 ABBV-368. Palliative radiation therapy for painful bone or skin metastasis for 10 fractions or less is not subject to a washout period.
2. Prior treatment with an OX40 targeting agent.
3. Subject has known uncontrolled metastases to the central nervous system (CNS).
4. Patients with known symptomatic brain metastases requiring systemic corticosteroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable. Mild neurological deficits are allowed, if they do not interfere with the ability to judge the safety profile of ABBV-368.
5. Subject has unresolved adverse events ≥ grade 2 from prior anticancer therapy except for alopecia.
6. History of or active autoimmune disorders (including but not limited to: Crohn's Disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that compromise or impair the immune system.
7. Active bacterial, fungal or viral infection including hepatitis B (HBV) or hepatitis C (HCV).
8. Subjects being considered for Parts 1 and 2A who have been previously treated with a PD1/PDL-1and/or OX40 targeting agent must not have had toxicities listed below during the course of their therapy:
-Any prior history of immune mediated pneumonitis, regardless of NCI CTCAE grade
-Any immune mediated toxicity of grade 3 or worse severity (including AST/ALT elevations that where considered drug related and cytokine release syndrome)
-Treatment of their toxicity with systemic corticosteroids or immune suppressive therapy
9. Subject has had major surgery ≤ 28 days prior to the first dose of ABBV-368 and the surgical wound is not fully healed.
10. Subject has a clinically significant uncontrolled condition(s) including but not limited to the following:
-Active uncontrolled infection
-Symptomatic congestive heart failure
-Unstable angina pectoris or cardiac arrhythmia
-Psychiatric illness/social situation that would limit compliance with the study
-Medical condition that requires chronic systemic therapy or requires immunosuppressive medication. Patients using physiological replacement doses of corticosteroids ≤ 10 mg of prednisone or equivalent (≥ 1.5 mg of dexamethasone) or its equivalent are eligible.
-Subject has history of major immunologic reaction to any IgG-containing agent.
-Active autoimmune disease, with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism, and psoriasis.
-Known immunosuppressive disease, for example human immunodeficiency virus infection or history of bone marrow transplant or chronic lymphocytic leukemia.
11. Subject has any medical condition which in the opinion of the Investigator or Medical Monitor places the subject at an unacceptably high risk for toxicities.
12. Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 4 months after the last dose of study drug.
13. Male subjects who are considering fathering a child or donating sperm during the study or for approximately 4 months after the last dose of study drug.
2. Prior treatment with an OX40 targeting agent.
3. Subject has known uncontrolled metastases to the central nervous system (CNS).
4. Patients with known symptomatic brain metastases requiring systemic corticosteroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable. Mild neurological deficits are allowed, if they do not interfere with the ability to judge the safety profile of ABBV-368.
5. Subject has unresolved adverse events ≥ grade 2 from prior anticancer therapy except for alopecia.
6. History of or active autoimmune disorders (including but not limited to: Crohn's Disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, Grave's disease) and other conditions that compromise or impair the immune system.
7. Active bacterial, fungal or viral infection including hepatitis B (HBV) or hepatitis C (HCV).
8. Subjects being considered for Parts 1 and 2A who have been previously treated with a PD1/PDL-1and/or OX40 targeting agent must not have had toxicities listed below during the course of their therapy:
-Any prior history of immune mediated pneumonitis, regardless of NCI CTCAE grade
-Any immune mediated toxicity of grade 3 or worse severity (including AST/ALT elevations that where considered drug related and cytokine release syndrome)
-Treatment of their toxicity with systemic corticosteroids or immune suppressive therapy
9. Subject has had major surgery ≤ 28 days prior to the first dose of ABBV-368 and the surgical wound is not fully healed.
10. Subject has a clinically significant uncontrolled condition(s) including but not limited to the following:
-Active uncontrolled infection
-Symptomatic congestive heart failure
-Unstable angina pectoris or cardiac arrhythmia
-Psychiatric illness/social situation that would limit compliance with the study
-Medical condition that requires chronic systemic therapy or requires immunosuppressive medication. Patients using physiological replacement doses of corticosteroids ≤ 10 mg of prednisone or equivalent (≥ 1.5 mg of dexamethasone) or its equivalent are eligible.
-Subject has history of major immunologic reaction to any IgG-containing agent.
-Active autoimmune disease, with exceptions of vitiligo, type I diabetes mellitus, hypothyroidism, and psoriasis.
-Known immunosuppressive disease, for example human immunodeficiency virus infection or history of bone marrow transplant or chronic lymphocytic leukemia.
11. Subject has any medical condition which in the opinion of the Investigator or Medical Monitor places the subject at an unacceptably high risk for toxicities.
12. Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 4 months after the last dose of study drug.
13. Male subjects who are considering fathering a child or donating sperm during the study or for approximately 4 months after the last dose of study drug.
The Estimated Number of Participants
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Taiwan
15 participants
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Global
180 participants
