Clinical trial NCT05501821: Study of KBA1412 in Participants With Advanced Solid Malignant Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumor Malignancy
Keywords: solid tumor adult
refractory cancer
Lead sponsor: Kling Biotherapeutics B.V.
Sponsor class: INDUSTRY
First posted: 2022-08-15
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part A will consist of multiple cohorts, each at an escalated dose level of KBA1412.

Part B will consist of disease specific cohorts, each cohort treated with KBA1412 at a fixed dose level.

Part C will consist of disease specific cohorts, each cohort treated with KBA1412 at a fixed dose in combination with pembrolizumab at a fixed dose.
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Part A & B & C: Frequency and severity of AEs as assessed by CTCAE v5.0
timeFrame: Through study completion, an average of 1 year
measure: Part A: Frequency and type of DLT s using the CTCAE v5.0
timeFrame: First 21 days of treatment
measure: Number of participants with an antitumor response to KBA1412 monotherapy (Part B) or to KBA1412 in combination with pembrolizumab (Part C)
timeFrame: Approximately 24 weeks
Secondary outcomes:
measure: Part A: Number of participants with an antitumor response to KBA1412 monotherapy
timeFrame: Approximately 24 weeks
measure: Pharmacokinetic of KBA1412 monotherapy (Part A & B) and KBA1412 in combination with pembrolizumab (Part C), area under the concentration versus time curve (AUC)
timeFrame: Approximately 24 weeks
measure: Incidence and prevalence of anti-KBA1412 antibodies for KBA1412 monotherapy (Part A & B) and KBA1412 in combination with pembrolizumab (Part C)
timeFrame: Approximately 24 weeks
measure: Change in biomarkers for KBA1412 monotherapy (Part A & B) and KBA1412 in combination with pembrolizumab (Part C) pre- and post-dose in tumor tissue
timeFrame: Approximately 24 weeks
Other outcomes:
Locations:
city: Antwerp
country: Belgium
facility: University Hospital Antwerp
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Amsterdam
country: Netherlands
facility: Dutch Cancer Institute AVL
city: Leiden
country: Netherlands
facility: University Hospital Leiden (LUMC)
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center Rotterdam
Study officials:
References: