melanoma Solid Tumors
Conditions
Interventions
The IMP will be administered
Sponsors
Kling Biotherapeutics B.V.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
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)
Exclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Escalation Phase: Part A & mini-dose escalation part C: Primary endpoint: • To determine the DLT's. • To establish the MTD and/or RP2D of single agent KBA1412 and KBA1412 plus pembrolizumab Expansion Phase: Parts B and C: Primary endpoint: • To determine safety and tolerability using the secondary safety outcome measures: Incidence, nature, and severity of adverse events; changes in physical examination findings, laboratory test results, and vital signs over time. • To establish the MTD and/or RP2D of single agent KBA1412 and KBA1412 plus pembrolizumab. • To evaluate the objective response rate (ORR) in each of the cohorts using iRECIST. Dose Escalation Phase: Part A & mini-dose escalation part C: Timepoint of evaluation: • at completion of DLT observation period Expansion Phase: Parts B and C: Timepoint of evaluation: • at completion of cycle 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Dose Escalation Phase: Part A & mini-dose escalation part C: Secondary endpoint: • To determine the serum PK profile of KBA1412 monotherapy and KBA1412 plus pembrolizumab. • To determine the Incidence of antibody formation to KBA1412 monotherapy and KBA1412 plus pembrolizumab. •To determine the objective response rate (ORR) in each of the cohorts using iRECIST. Expansion Phase: Parts B and C: Secondary endpoint: • To determine the serum PK profile of KBA1412 monotherapy and KBA1412 plus pembrolizumab. • To determine the Incidence of antibody formation to KBA1412 monotherapy and KBA1412 plus pembrolizumab. Timepoint of evaluation: • at completion of treatment of the last patient in Part A (patients of Part C mini-dose escalation will continue in dose expansion) Expansion Phase: Parts B and C: Timepoint of evaluation: • at completion of treatment of the last patient in Part B and Part C | — |
Countries
Netherlands
Outcome results
None listed