Study of KBA1412 in Participants With Advanced Solid Malignant Tumors

Advanced Solid Tumor Malignancy Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05501821
• Other study ID #: KBA1412-101
• Status: Recruiting
• Phase: Phase 1
• Start date: August 8, 2022
• Est. completion date: January 2025

Study information

• Verified date: November 2023
• Source: Kling Biotherapeutics B.V.
• Contact: Peter Holleman
• Phone: +31629534888
• Email: peter[@]klingbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 106
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumor Malignancy
• Neoplasms

Intervention

Drug:
• KBA1412
Part A, B, C
• Pembrolizumab
Part C only

Locations

Country	Name	City	State
Belgium	University Hospital Antwerp	Antwerp
Belgium	University Hospital Ghent	Ghent
Netherlands	Dutch Cancer Institute AVL	Amsterdam
Netherlands	University Hospital Leiden (LUMC)	Leiden
Netherlands	Erasmus Medical Center Rotterdam	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Kling Biotherapeutics B.V.

Countries where clinical trial is conducted

Belgium,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A & B & C: Frequency and severity of AEs as assessed by CTCAE v5.0	Monitoring incidence and severity of Adverse Events during trial participation for each participant	Through study completion, an average of 1 year
Primary	Part A: Frequency and type of DLT s using the CTCAE v5.0	A DLT is defined as an adverse event that is unrelated to disease progression, intercurrent illness, or concomitant medications and is occurring during the first 21 days of treatment. These events will be classified according to the CTCAE v5.0	First 21 days of treatment
Primary	Number of participants with an antitumor response to KBA1412 monotherapy (Part B) or to KBA1412 in combination with pembrolizumab (Part C)	Response according to immune Response Evaluation Criteria in Solid Tumors (iRECIST)	Approximately 24 weeks
Secondary	Part A: Number of participants with an antitumor response to KBA1412 monotherapy	Response according to immune Response Evaluation Criteria in Solid Tumors (iRECIST)	Approximately 24 weeks
Secondary	Pharmacokinetic of KBA1412 monotherapy (Part A & B) and KBA1412 in combination with pembrolizumab (Part C), area under the concentration versus time curve (AUC)	Area under the plasma concentration versus time curve (AUC) of KBA1412 will be assessed in all participants	Approximately 24 weeks
Secondary	Incidence and prevalence of anti-KBA1412 antibodies for KBA1412 monotherapy (Part A & B) and KBA1412 in combination with pembrolizumab (Part C)	Development of antibodies (anti-drug antibodies) to KBA1412 will be evaluated for all participants	Approximately 24 weeks
Secondary	Change in biomarkers for KBA1412 monotherapy (Part A & B) and KBA1412 in combination with pembrolizumab (Part C) pre- and post-dose in tumor tissue	Change in pharmacodynamic properties of KBA1412 pre- and post-dose in immune infiltration, activation and cytotoxicity assessed by Immunohistochemistry	Approximately 24 weeks