Clinical trial NCT04294576: Safety Study of BJ-001, an IL-15 Fusion Protein, for Locally Advanced/Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Locally Advanced/Metastatic Solid Tumors
Keywords: FIH
Solid Tumors
Lead sponsor: BJ Bioscience, Inc.
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
name: Merck Sharp & Dohme LLC
First posted: 2020-03-04
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of adverse events (AEs) and SAE
timeFrame: 90 days after the last dose
measure: Severity of AEs in patients with solid tumors enrolled in the study.
timeFrame: From Day 1 of treatment up to 30 days after last dose
measure: Dose limiting toxicities (DLTs) BJ-001 as a single agent
timeFrame: at the end of week 4 after first dose
measure: Dose limiting toxicities (DLTs) BJ-001 in combination with pembrolizumab inhibitor.
timeFrame: at the end of week 4 after first dose
Secondary outcomes:
measure: Immunogenicity of BJ-001 as a single agent and in combination with Pembrolizumab.
timeFrame: 90 days after last dose
measure: Pharmacokinetic (PK) AUC0-τ samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.
timeFrame: 24 weeks
measure: Pharmacokinetic (PK) Cmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.
timeFrame: 24 weeks
measure: Pharmacokinetic (PK) Ctrough samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.
timeFrame: 24 weeks
measure: Pharmacokinetic (PK) Tmax samples patients treated with BJ-001 as a single agent and in combination with Pembrolizumab.
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Mount Sinai
state: New York
city: Greenville
country: United States
facility: Greenville Hospital System University Medical Center (ITOR)
state: South Carolina
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Tacoma
country: United States
facility: Northwest Medical Specialities
state: Washington
Study officials:
affiliation: BJ Bioscience
name: Joe Zhang, PhD
role: STUDY_DIRECTOR
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