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

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.

no masking is used. All involved know the identity of the intervention assignment.