Safety Study of BJ-001, an IL-15 Fusion Protein, for Locally Advanced/Metastatic Solid Tumors

Study Overview
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Brief Summary
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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

Official Title
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First-in-human (FIH), Open-Label, Phase 1a (Dose Escalation)/Phase 1b (Expansion Cohort) Trial of BJ-001 as a Single Agent and in Combination With Pembrolizumab in Patients With Locally Advanced/Metastatic Solid Tumors

Conditions
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Locally Advanced/Metastatic Solid Tumors

Intervention / Treatment
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* Drug: BJ-001
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase 1a patients must have locally advanced or metastatic solid tumors, 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) 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 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. 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. Adequate hematologic function, Adequate hepatic function, defined by all of the following: Adequate renal function defined by estimated creatinine clearance ≥ 45 mL/min (Cockcroft and Gault formula ECOG Performance Status (PS) of 0-2. No history of any hematopoietic malignancy. No active or history of clinically significant autoimmune disease (as defined by previously requiring immunosuppressive therapy). Exclusion Criteria: Pregnant or nursing females. 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). 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, Patients with a history of severe allergic or anaphylactic reactions to human mAb therapy or known hypersensitivity. Patients with a history of pneumonitis, myocarditis, history of Stevens-Johnson syndrome or toxic epidermal necrolysis. Patients who have undergone a bone marrow transplantation, solid organ transplantation, or stem cell transplant. Patients with unresolved AEs > Grade 1 from prior anticancer therapy. Patients who have received prior interferon or IL-2 therapy less than 4 weeks prior to enrollment. Uncontrolled primary central nervous system (CNS) tumors or CNS metastases; based on screening. Patients with active autoimmune disease or a documented medical history of autoimmune disease managed by replacement therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1; BJ-001<br>Phase 1a Part 1, Part 2, and Part 4: dose escalation for BJ-001 as single agent | Drug: BJ-001<br>* BJ-001 dosed via SC injection as single agent. One cycle is 6 weeks.<br>|
| Experimental: Arm 2; BJ-001 and pembrolizumab<br>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<br>* BJ-001 dosed via SC injection as single agent. One cycle is 6 weeks.<br>Drug: Pembrolizumab<br>* BJ-001 dosed via SC injection in combination with Pembrolizumab One cycle is 6 weeks.<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of adverse events (AEs) and SAE | 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. | 90 days after the last dose | 
| Severity of AEs in patients with solid tumors enrolled in the study. | 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. | From Day 1 of treatment up to 30 days after last dose | 
| Dose limiting toxicities (DLTs) BJ-001 as a single agent | To determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of BJ-001 as a single agent. | at the end of week 4 after first dose | 
| Dose limiting toxicities (DLTs) BJ-001 in combination with pembrolizumab inhibitor. | 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. | at the end of week 4 after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of BJ-001 as a single agent and in combination with Pembrolizumab. | The frequency of anti-drug antibodies (ADA) against BJ-001 as a single agent and in combination with Pembrolizumab. | 90 days after last dose | 
| Pharmacokinetic (PK) AUC0-τ samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. | PK parameters (AUC0-τ) following the first dose and the fourth dose | 24 weeks | 
| Pharmacokinetic (PK) Cmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. | PK parameters (Cmax) following the first dose and the fourth dose | 24 weeks | 
| Pharmacokinetic (PK) Ctrough samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. | PK parameters (Ctrough) following the first dose and the fourth dose | 24 weeks | 
| Pharmacokinetic (PK) Tmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab. | PK parameters (Tmax) following the first dose and the fourth dose | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FIH, Solid Tumors