FIH: Safety Study of BJ-001, an IL-15 Fusion Protein, for Locally Advanced/Metastatic Solid Tumors
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the safety and tolerability of BJ-001, a human IL-15 fusion protein, administered via subcutaneous injections, as a single agent and in combination with pembrolizumab in adult patients with Locally Advanced/Metastatic Solid Tumors
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1; BJ-001 Phase 1a Part 1, Part 2, and Part 4: dose escalation for BJ-001 as single agent |
Drug: BJ-001
BJ-001 dosed via SC injection as single agent. One cycle is 6 weeks.
|
| Experimental: Arm 2; BJ-001 and pembrolizumab Phase 1a Part 3 and Part 5: dose escalation for BJ-001 in combination with Pembrolizumab Phase 1b: expansion cohorts for the combination of BJ-001 and pembrolizumab |
Drug: BJ-001
BJ-001 dosed via SC injection as single agent. One cycle is 6 weeks.
Drug: Pembrolizumab
BJ-001 dosed via SC injection in combination with Pembrolizumab
One cycle is 6 weeks.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Frequency of adverse events (AEs) and SAE [90 days after the last dose]
To assess the safety and tolerability of BJ-001 as a single agent administered s.c. at escalating dose levels in adults with solid tumors.
- Severity of AEs in patients with solid tumors enrolled in the study. [From Day 1 of treatment up to 30 days after last dose]
To assess the safety and tolerability of s.c. BJ-001 administered at escalating dose levels in combination with Pembrolizumab inhibitor. in adults with solid tumors.
- Dose limiting toxicities (DLTs) BJ-001 as a single agent [at the end of week 4 after first dose]
To determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of BJ-001 as a single agent.
- Dose limiting toxicities (DLTs) BJ-001 in combination with pembrolizumab inhibitor. [at the end of week 4 after first dose]
To determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of s.c. BJ-001 administered at escalating dose levels in combination with pembrolizumab in adults with solid tumors.
Secondary Outcome Measures
- Immunogenicity of BJ-001 as a single agent and in combination with Pembrolizumab. [90 days after last dose]
The frequency of anti-drug antibodies (ADA) against BJ-001 as a single agent and in combination with Pembrolizumab.
- Pharmacokinetic (PK) AUC0-τ samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. [24 weeks]
PK parameters (AUC0-τ) following the first dose and the fourth dose
- Pharmacokinetic (PK) Cmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. [24 weeks]
PK parameters (Cmax) following the first dose and the fourth dose
- Pharmacokinetic (PK) Ctrough samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. [24 weeks]
PK parameters (Ctrough) following the first dose and the fourth dose
- Pharmacokinetic (PK) Tmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. [24 weeks]
PK parameters (Tmax) following the first dose and the fourth dose
Eligibility Criteria
Criteria
Inclusion Criteria:
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Phase 1a patients must have locally advanced or metastatic solid tumors,
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Phase 1b patients must have locally advanced or metastatic and/or non-resectable head and neck squamous cell carcinoma, cholangiocarcinoma, stomach cancer, melanoma, pancreatic cancer, NSCLC (as high expression of αVβ3, αVβ5, or αVβ6 have been reported for these tumors)
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Measurable disease: For Phase 1a patients can have non-measurable or measurable disease. For all other parts: measurable disease defined by RECIST v1.1 is required
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For Phase 1a Part 3 and Phase 1b patients (combination treatment) must be refractory or relapsed to anti-PD-1, anti-PD-L1 or anti-CTLA4 checkpoint inhibitors for all tumor types, For Part 1 and Part 2 of Phase 1a (BJ-001 single agent treatment) both checkpoint inhibitor naïve or refractory/relapsed patients will be considered.
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Patient who have diagnosis for which treatment with pembrolizumab to be enrolled. Patients previously treated with pembrolizumab and who have progressed are eligible. to be enrolled.
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Adequate hematologic function,
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Adequate hepatic function, defined by all of the following:
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Adequate renal function defined by estimated creatinine clearance ≥ 45 mL/min (Cockcroft and Gault formula
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ECOG Performance Status (PS) of 0-2.
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No history of any hematopoietic malignancy.
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No active or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy).
Exclusion Criteria:
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Pregnant or nursing females.
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Receipt of any investigational product or any approved anticancer drug(s) or biological product(s) within 4 weeks prior to the first dose of study drug. Exceptions: Hormone replacement therapy, testosterone, or oral contraceptives (LHRH antagonists are allowed).
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Patients previously treated with an anti PD-1/PD-L1 targeting agent who have had any prior history of immune-mediated pneumonitis, any immune-mediated toxicity of ≥ Grade 3,
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Patients with a history of severe allergic or anaphylactic reactions to human mAb therapy or known hypersensitivity.
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Patients with a history of pneumonitis, myocarditis, history of Stevens-Johnson syndrome or toxic epidermal necrolysis.
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Patients who have undergone a bone marrow transplantation, solid organ transplantation, or stem cell transplant.
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Patients with unresolved AEs > Grade 1 from prior anticancer therapy.
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Patients who have received prior interferon or IL-2 therapy less than 4 weeks prior to enrollment.
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Uncontrolled primary central nervous system (CNS) tumors or CNS metastases; based on screening.
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Patients with active autoimmune disease or a documented medical history of autoimmune disease managed by replacement therapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 2 | Mount Sinai | New York | New York | United States | 10029 |
| 3 | Greenville Hospital System University Medical Center (ITOR) | Greenville | South Carolina | United States | 29605 |
| 4 | NEXT Oncology | San Antonio | Texas | United States | 78229 |
| 5 | Northwest Medical Specialities | Tacoma | Washington | United States | 98405 |
Sponsors and Collaborators
- BJ Bioscience, Inc.
- Iqvia Pty Ltd
- PPD
Investigators
- Study Director: Leijun Hu, PhD, BJ Bioscience
Study Documents (Full-Text)
None provided.More Information
Additional Information:
- KEYTRUDA (pembrolizumab), [package insert]. Merck Sharp & Dohme Corp. Whitehouse Station, NJ.2014. Accessed at Drugs@FDA: FDA Approved Drug Products on December 28, 2018.
- OPDIVO (nivolumab), [package insert]. Bristol-Myers Squibb Company, Princeton, NJ. 2014. Accessed at Drugs@FDA: FDA Approved Drug Products on November 15, 2018.
- TECENTRIQ (atezolizumab), [package insert]. Genentech, Inc. San Francisco, CA. 2016. Accessed at Drugs@FDA: FDA Approved Drug Products on December 6, 2018.
- YERVOY (ipilimumab), [package insert]. Bristol-Myers Squibb Company, Princeton, NJ. 2011. Accessed at Drugs@FDA: FDA Approved Drug Products on July 10, 2018.
Publications
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- BJ-001-01-001US