Clinical Trials List
Protocol NumberBA3021-001
NCT Number(ClinicalTrials.gov Identfier)NCT03504488
2019-09-01 - 2024-12-31
Phase I/II
Recruiting4
ICD-9199.0
Disseminated malignant neoplasm
A Phase 1/2 Dose Escalation and Dose Expansion Study of BA3021 in Patients With Advanced Solid Tumors
-
Trial Applicant
COVANCE TAIWAN SERVICES LIMITED
-
Sponsor
BioAtla Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Wen-Pin Su 未分科
- Po-Lan Su 未分科
- Wu-Chou Su Division of General Internal Medicine
- Shang-Yin Wu 未分科
- Jui-Hung Tsai 未分科
- Chien-Chung Lin 未分科
- Wei-Pang Chung Division of General Internal Medicine
- Chun-Hui Lee 未分科
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tai-Jan Chiu Division of Hematology & Oncology
- 林孟志 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Tsai-Sheng Yang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- James Chih-Hsin Yang Division of Hematology & Oncology
- Chong-Jen Yu Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Advanced Solid Tumors
Objectives
Phase 1 (Dose-Escalation Phase) Objectives:Primary:• To define the safety profile, including dose-limiting toxicity (DLT), and determine themaximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), of BA3021administered in a 21-day cycle in patients with advanced solid tumors.Secondary:• To assess the pharmacokinetics (PK) of BA3021 in patients with advanced solid tumors.• To assess the antitumor activity of BA3021.• To evaluate the immunogenicity of BA3021.Phase 2 (Dose-Expansion Phase) Objectives:Primary:• To assess antitumor activity of BA3021 in patients with specified tumor types.• To assess the safety of BA3021.Secondary:• To assess the PK of BA3021 in patients with advanced solid tumors.• To evaluate the immunogenicity of BA3021. Exploratory:• To explore the relationship between tumor receptor tyrosine kinase orphan receptor 2 (ROR2)status and clinical response to BA3021 in patients with specified tumors.• To evaluate potential candidate tumor and blood-based biomarkers for patient selection orcorrelation with antitumor activity of BA3021.
Test Drug
BA3021
Active Ingredient
CAB-ROR2-ADC
Dosage Form
IV infusion
Dosage
5ml/vial (10 mg/ml)
Endpoints
Primary Endpoints
• Safety: DLTs, MTD (Phase 1), adverse events (AEs), serious adverse events (SAEs), and
changes from baseline in laboratory parameters and vital signs.
• Efficacy (Phase 2): objective response rate (ORR) according to Response Evaluation
Criteria in Solid Tumors (RECIST) Version 1.1.
Secondary Endpoints
• Efficacy (Phase 2 and Phase 1 cohort expansion): objective response (OR), disease
control, time-to-response, duration of response (DOR), progression-free survival (PFS),
OS, and change from baseline in tumor size, according to RECIST Version 1.1.
• Pharmacokinetics of BA3021: plasma concentrations of ADC, total antibody and
MMAE, and PK parameters, including Cmax and AUC.
• Immunogenicity of BA3021: the number and percentage of patients who develop
detectable anti-drug antibodies (ADAs).
Exploratory Endpoints
• Phase 2 only: Relationship between tumor ROR2 status and clinical response to BA3021
in patients with specified tumors.
• Phase 2 only: Potential candidate tumor and blood-based biomarkers for patient selection
or correlation with antitumor activity of BA3021.
• Safety: DLTs, MTD (Phase 1), adverse events (AEs), serious adverse events (SAEs), and
changes from baseline in laboratory parameters and vital signs.
• Efficacy (Phase 2): objective response rate (ORR) according to Response Evaluation
Criteria in Solid Tumors (RECIST) Version 1.1.
Secondary Endpoints
• Efficacy (Phase 2 and Phase 1 cohort expansion): objective response (OR), disease
control, time-to-response, duration of response (DOR), progression-free survival (PFS),
OS, and change from baseline in tumor size, according to RECIST Version 1.1.
• Pharmacokinetics of BA3021: plasma concentrations of ADC, total antibody and
MMAE, and PK parameters, including Cmax and AUC.
• Immunogenicity of BA3021: the number and percentage of patients who develop
detectable anti-drug antibodies (ADAs).
Exploratory Endpoints
• Phase 2 only: Relationship between tumor ROR2 status and clinical response to BA3021
in patients with specified tumors.
• Phase 2 only: Potential candidate tumor and blood-based biomarkers for patient selection
or correlation with antitumor activity of BA3021.
Inclution Criteria
Inclusion Criteria
Potential patients must sign an informed consent form before any study-specific screening
tests may be conducted. Screening tests are described in Section 6.1.
1. Patients must have histologically or cytologically confirmed locally advanced unresectable or
metastatic solid tumor and have failed all available standard of care (SoC) therapy and for
whom no curative therapy is available or who are not eligible, intolerant to or refuse standard
therapy.
2. Patients with specified solid tumors must have measurable disease according to RECIST 1.1.
Previously radiated tumor lesion should not be considered a target lesion.
3. Archived tissue or tissue from a tumor amenable to biopsy must be available and must be
confirmed prior to receiving BA3021.
4. The following tumor types will be included in patients in Phase 1 cohort expansion and Phase
2; patients must have ROR2-positive disease as determined by BioAtla ROR2 assay based on
archival tissue or biopsy (ROR2 expression cutoff: ≥ 1+ in ≥ 10% tumor cells):
- Stage IIIB/IV NSCLC: patients who previously received no more than 5 prior lines of
SoC therapy.
- Triple negative breast cancer: patients with diagnosis of TNBC (estrogen, progesterone,
and human epidermal growth factor receptor 2 (HER2)-negative carcinoma of the
breast); no limit to the number of prior systemic therapies.
- Soft tissue sarcoma: patients with diagnosis of soft tissue sarcoma who had failed
standard chemotherapy; no limit to the number of prior systemic therapies.
5. Patients must be age ≥ 18 years.
6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1.
7. Patients must have a life expectancy of at least 3 months.
8. Tissue must be available to the Sponsor for ROR2 and other gene expression testing. All
patients must consent to provide a pretreatment tumor specimen within 12 months of the first
dose of BA3021 for biomarker studies. Archival tumor tissue must be identified and
availability confirmed prior to study treatment initiation. In the setting where archival tissue
is unavailable, patients must consent to undergo a tumor biopsy during screening. Sites are
encouraged to confirm adequacy of tumor biopsy material at the time of the procedure.
Additional older archival tumor samples regardless of age are also required, if available. The
confirmation of receipt of the tissue and ROR2 positivity by the central vendor will be
required at Phase 2 prior to enrollment. A fine needle aspirate or cytologic specimen will not
be acceptable. Core needle (a minimum of 3 core samples are required) or excisional biopsies, or resected tissue is required. Phase 1 cohort expansion requires the confirmation
of ROR2 positivity by the central vendor prior to enrollment.
9. Patients must have:
- Completed (and recovered from treatment-related toxicities) any prior treatment with
radiotherapy, chemotherapy, or targeted small molecule therapy and/or treatment with
other investigational anticancer agents at least 5 half-lives or 2 weeks prior to first
study dose, or biologics (such as a monoclonal antibody) at least 4 weeks prior to first
study dose. Exceptions are bisphosphonates, denosumab and gonadotropin-releasing
hormone agonist or antagonist.
- Completed any prior treatment with nitrogen mustard agents, melphalan, or carmustine
(BCNU) therapy at least 6 weeks prior to first study dose.
- Received any prior autologous hematopoietic stem cell infusion at least 8 weeks prior
to first study dose.
10. Patients must have adequate organ functions. The following are required baseline laboratory
values:
- Absolute neutrophil count ≥ 1,500/μL or 1.5 x 109
/L.
- Platelets ≥ 100,000/µL or 100 x 109
/L.
- Hemoglobin ≥ 9.0 g/dL.
- Bilirubin ≤ 1.5 x upper limit of normal (ULN).
- Serum creatinine ≤ 1.5 x ULN.
- ALT and AST ≤ 2.5 x ULN; ALT and AST ≤ 5 x ULN if metastasis in liver.
11. Patients must be available for periodic blood sampling, study-related assessments and
management of toxicity at the treating institution and be willing to comply with the expected
drug administration schedule.
12. Females of childbearing potential must have a negative serum or urine pregnancy test result
prior to the first dose of BA3021 and must agree to use an effective contraceptive method,
either a barrier/intrauterine method or a hormonal method, during the course of the study.
- Females of non-child-bearing potential are those who are postmenopausal greater than
1 year or who have had a bilateral tubal ligation or hysterectomy.
- Both females and males of childbearing/reproductive potential must agree to use
adequate contraception while included in the study and for 6 months after the last
infusion of BA3021.
13. Patients or their legally authorized representative must provide written informed consent.
Potential patients must sign an informed consent form before any study-specific screening
tests may be conducted. Screening tests are described in Section 6.1.
1. Patients must have histologically or cytologically confirmed locally advanced unresectable or
metastatic solid tumor and have failed all available standard of care (SoC) therapy and for
whom no curative therapy is available or who are not eligible, intolerant to or refuse standard
therapy.
2. Patients with specified solid tumors must have measurable disease according to RECIST 1.1.
Previously radiated tumor lesion should not be considered a target lesion.
3. Archived tissue or tissue from a tumor amenable to biopsy must be available and must be
confirmed prior to receiving BA3021.
4. The following tumor types will be included in patients in Phase 1 cohort expansion and Phase
2; patients must have ROR2-positive disease as determined by BioAtla ROR2 assay based on
archival tissue or biopsy (ROR2 expression cutoff: ≥ 1+ in ≥ 10% tumor cells):
- Stage IIIB/IV NSCLC: patients who previously received no more than 5 prior lines of
SoC therapy.
- Triple negative breast cancer: patients with diagnosis of TNBC (estrogen, progesterone,
and human epidermal growth factor receptor 2 (HER2)-negative carcinoma of the
breast); no limit to the number of prior systemic therapies.
- Soft tissue sarcoma: patients with diagnosis of soft tissue sarcoma who had failed
standard chemotherapy; no limit to the number of prior systemic therapies.
5. Patients must be age ≥ 18 years.
6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
or 1.
7. Patients must have a life expectancy of at least 3 months.
8. Tissue must be available to the Sponsor for ROR2 and other gene expression testing. All
patients must consent to provide a pretreatment tumor specimen within 12 months of the first
dose of BA3021 for biomarker studies. Archival tumor tissue must be identified and
availability confirmed prior to study treatment initiation. In the setting where archival tissue
is unavailable, patients must consent to undergo a tumor biopsy during screening. Sites are
encouraged to confirm adequacy of tumor biopsy material at the time of the procedure.
Additional older archival tumor samples regardless of age are also required, if available. The
confirmation of receipt of the tissue and ROR2 positivity by the central vendor will be
required at Phase 2 prior to enrollment. A fine needle aspirate or cytologic specimen will not
be acceptable. Core needle (a minimum of 3 core samples are required) or excisional biopsies, or resected tissue is required. Phase 1 cohort expansion requires the confirmation
of ROR2 positivity by the central vendor prior to enrollment.
9. Patients must have:
- Completed (and recovered from treatment-related toxicities) any prior treatment with
radiotherapy, chemotherapy, or targeted small molecule therapy and/or treatment with
other investigational anticancer agents at least 5 half-lives or 2 weeks prior to first
study dose, or biologics (such as a monoclonal antibody) at least 4 weeks prior to first
study dose. Exceptions are bisphosphonates, denosumab and gonadotropin-releasing
hormone agonist or antagonist.
- Completed any prior treatment with nitrogen mustard agents, melphalan, or carmustine
(BCNU) therapy at least 6 weeks prior to first study dose.
- Received any prior autologous hematopoietic stem cell infusion at least 8 weeks prior
to first study dose.
10. Patients must have adequate organ functions. The following are required baseline laboratory
values:
- Absolute neutrophil count ≥ 1,500/μL or 1.5 x 109
/L.
- Platelets ≥ 100,000/µL or 100 x 109
/L.
- Hemoglobin ≥ 9.0 g/dL.
- Bilirubin ≤ 1.5 x upper limit of normal (ULN).
- Serum creatinine ≤ 1.5 x ULN.
- ALT and AST ≤ 2.5 x ULN; ALT and AST ≤ 5 x ULN if metastasis in liver.
11. Patients must be available for periodic blood sampling, study-related assessments and
management of toxicity at the treating institution and be willing to comply with the expected
drug administration schedule.
12. Females of childbearing potential must have a negative serum or urine pregnancy test result
prior to the first dose of BA3021 and must agree to use an effective contraceptive method,
either a barrier/intrauterine method or a hormonal method, during the course of the study.
- Females of non-child-bearing potential are those who are postmenopausal greater than
1 year or who have had a bilateral tubal ligation or hysterectomy.
- Both females and males of childbearing/reproductive potential must agree to use
adequate contraception while included in the study and for 6 months after the last
infusion of BA3021.
13. Patients or their legally authorized representative must provide written informed consent.
Exclusion Criteria
Exclusion Criteria
1. Patients must not have clinically significant cardiac disease, in the judgment of the
Investigator.
2. Patients must not have known congestive heart failure (New York Heart Association classes
II-IV) or serious cardiac arrhythmia requiring treatment; patients with stable condition and
medication for ≥ 3 months can be enrolled.
3. Patients must not have known non-controlled central nervous system (CNS) metastasis.
4. Patients must not have received granulocyte colony stimulating factor (G-CSF) or
granulocyte/macrophage colony stimulating factor support 3 weeks prior to first BA3021
administration.
5. Patients must not have a history of ≥ Grade 3 allergic reactions to monoclonal antibody
therapy as well as known or suspected allergy or intolerance to any agent given during this
study.
6. Patients must not have had major surgery within 4 weeks before first BA3021 administration.
7. Patients must not have any history of intracerebral arteriovenous malformation, cerebral
aneurysm, or stroke.
8. Patients must not have had prior therapy with a conjugated or unconjugated auristatin
derivative/vinca-binding site targeting payload.
9. Patients must not have known additional malignancy that is active and/or progressive
requiring treatment; patients with other malignancies that have been definitively treated and
who have been rendered disease free will be eligible.
10. Patients must not have Grade 2 or higher peripheral neuropathy.
11. Patients must not have clinically significant (in the judgment of the Investigator) active viral,
bacterial or fungal infection requiring systemic antibiotics/antivirals/antifungals.
12. Patients must not have known human immunodeficiency virus (HIV) infection, active
hepatitis B and/or hepatitis C.
13. Patients must not be women who are pregnant or breast feeding.
14. Patients must not be using concurrent therapy with other anti-neoplastic or experimental
agents.
15. Patients must not be using concurrent therapy with corticosteroids at greater than or equal to
12 mg/day prednisone equivalent.
16. Patients must not have any serious underlying medical condition that, in the opinion of the
Investigator or Medical Monitor, would impair their ability to receive or tolerate the planned
treatment. In such cases, the Sponsor-designated Medical Monitor must review each case
prior to patient enrollment.
1. Patients must not have clinically significant cardiac disease, in the judgment of the
Investigator.
2. Patients must not have known congestive heart failure (New York Heart Association classes
II-IV) or serious cardiac arrhythmia requiring treatment; patients with stable condition and
medication for ≥ 3 months can be enrolled.
3. Patients must not have known non-controlled central nervous system (CNS) metastasis.
4. Patients must not have received granulocyte colony stimulating factor (G-CSF) or
granulocyte/macrophage colony stimulating factor support 3 weeks prior to first BA3021
administration.
5. Patients must not have a history of ≥ Grade 3 allergic reactions to monoclonal antibody
therapy as well as known or suspected allergy or intolerance to any agent given during this
study.
6. Patients must not have had major surgery within 4 weeks before first BA3021 administration.
7. Patients must not have any history of intracerebral arteriovenous malformation, cerebral
aneurysm, or stroke.
8. Patients must not have had prior therapy with a conjugated or unconjugated auristatin
derivative/vinca-binding site targeting payload.
9. Patients must not have known additional malignancy that is active and/or progressive
requiring treatment; patients with other malignancies that have been definitively treated and
who have been rendered disease free will be eligible.
10. Patients must not have Grade 2 or higher peripheral neuropathy.
11. Patients must not have clinically significant (in the judgment of the Investigator) active viral,
bacterial or fungal infection requiring systemic antibiotics/antivirals/antifungals.
12. Patients must not have known human immunodeficiency virus (HIV) infection, active
hepatitis B and/or hepatitis C.
13. Patients must not be women who are pregnant or breast feeding.
14. Patients must not be using concurrent therapy with other anti-neoplastic or experimental
agents.
15. Patients must not be using concurrent therapy with corticosteroids at greater than or equal to
12 mg/day prednisone equivalent.
16. Patients must not have any serious underlying medical condition that, in the opinion of the
Investigator or Medical Monitor, would impair their ability to receive or tolerate the planned
treatment. In such cases, the Sponsor-designated Medical Monitor must review each case
prior to patient enrollment.
The Estimated Number of Participants
-
Taiwan
20 participants
-
Global
588 participants
