The purpose of this trial is to assess the safety and efficacy of KBA1412, a patient derived, fully human, monoclonal antibody targeting CD9, in patients with advanced solid malignant tumors

Patient interested in participation in a clinical study will be informed about the study and potential risks, all patients giving written informed consent will undergo a 3-week screening period to determine their eligibility for entry in the study. Patients will receive KBA1412 or KBA1412 in combination with pembrolizumab.

Inclusion criteria:

• Male or female patients aged ≥18 years.
• Histologically and/or cytologically confirmed locally advanced or metastatic solid tumors refractory to standard therapy or for whom no standard therapy is available.
• For Parts B and C, patients for whom anti-PD-1 or anti-programmed cell death ligand 1 (anti-PD-L1) are the SOC should have progressed on these therapies before being eligible for enrollment in Parts B and C. Patients cannot have received more than one anti-PD-1 or anti-PD-L1 based regimen.
• Disease accessible for core needle biopsy both pre- and post-treatment with KBA1412. Biopsies will be mandatory for patients with melanoma and required for other tumor types depending on feasibility of obtaining tissue.
• Measurable disease defined as: At least 1 lesion of ≥10 mm in the longest diameter for a non lymph node or ≥15 mm in the short-axis diameter for a lymph node that is serially measurable according to iRECIST using CT/MRI and will not be used for on-study paired biopsies.
• ECOG Performance Status of 0-1.
• Adequate hematologic, renal and hepatic function

Exclusion criteria:

• History of severe hypersensitivity reactions to other monoclonal antibodies.

• Prior treatment with:

  • Any chemotherapy, anticancer small molecule therapy or investigational drug or device within 14 days or 5 half-lives (whichever is longer) prior to study treatment administration
  • Biological agents (including monoclonal antibodies) within 28 days prior to study treatment administration
  • Radiation, within 14 days prior to study treatment administration
  • Treatment with nitrosoureas or mitomycin C require a 42-day washout prior to study treatment administration
  • Anti-CD40 antibody or with FMS-like tyrosine kinase 3 ligand (FLT3L)
  • KBA1412.

• Major surgery or significant traumatic injury within 4 weeks prior to study treatment administration.

• Excluding the primary tumor leading to enrollment in this study, any other active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the bladder or cervix) within 24 months prior to study treatment administration.

• Untreated primary central nervous system (CNS) malignancy.

• Use of immunosuppressive medications within 4 weeks or systemic corticosteroids at doses exceeding 10 mg/ day (prednisone equivalent) within 2 weeks prior to study treatment administration.

• Active autoimmune disease that has required systemic treatment within 2 years prior to study treatment administration.

• Clinically significant cardiovascular disease, e.g., cerebral vascular accident/stroke or myocardial infarction, within 6 months prior to study treatment administration, unstable angina, congestive heart failure (New York Heart Association [NYHA] Class ≥III), or unstable cardiac arrhythmia requiring medication.

• History of a major bleeding event (requiring a blood transfusion of >2 units) not related to a tumor within 12 months prior to study treatment administration.

• Ongoing Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 toxicity related to a previously administered anticancer agent with the following exceptions:

  • CTCAE Grade 2 neuropathy or alopecia
  • CTCAE Grade 2 immune-related endocrinopathy attributed to a checkpoint inhibitor and controlled with hormone replacement alone.