A Phase I, first-in-human, multicenter, open-label, dose escalation followed by an expansion phase clinical study of KBA1412 given as monotherapy or in combination with pembrolizumab in adults with advanced solid malignant tumors

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 22

Inclusion Criteria

• Male or female patients aged >=18 years with 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, tumor types are initially restricted to melanoma, ovarian
cancer, gastric cancer, and colorectal. Any additional tumor types may be added
as defined by the SRC.
• 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 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 Response Evaluation Criteria in
Solid Tumors for immunotherapy (iRECIST) using computerized tomography/magnetic
resonance imaging (CT/MRI) and will not be used for on-study paired biopsies.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.
• Adequate hematologic function as defined by:
- Absolute neutrophil count >= 1500/µL.
- Platelet count >=175.000/µL.
- Hemoglobin >= 9.0 g/dL (transfusion and growth factor independent).
- Prothrombin time/international normalized ratio (PT/INR) and partial
thromboplastin time (PTT) <=1.5 × upper limit of normal (ULN).

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.
• Primary central nervous system (CNS) malignancy.
Patients with stable CNS metastases post radiotherapy and no longer receiving
corticosteroids prior to study treatment administration, may be considered for
this study.
• 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.
• History of clinically significant coagulation or platelet disorder or a
history of being refractory to platelet transfusions within 12 months prior to
study treatment administration.
• Receiving or requiring anticoagulation therapy or any drug or herbal
supplements that affect platelet function, with exception of low-dose
anticoagulation medications that are used to maintain the patency of a central
IV catheter. Enrolment of a patient is allowed 2 weeks after stop of use of
anticoagulation therapy or medications.