A Study to Assess the Safety, Pharmacokinetics and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to characterize the safety and pharmacokinetic (PK) profile of UCB6114 administered as monotherapy or in combination with selected standard of care (SOC) regimens.

Official Title
-----------------
A Phase 1/2 Open-Label, Multicenter Study to Assess the Safety, Pharmacokinetics, and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors

Conditions
-----------------
Advanced Solid Tumors

Intervention / Treatment
-----------------
* Drug: ginisortamab
* Drug: trifluridine/tipiracil
* Drug: mFOLFOX6


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant must be at least 18 years of age inclusive, at the time of signing the informed consent Participant has advanced disease (ie, locally advanced or metastatic) Participant has measurable or non-measurable disease as defined by the relevant Response Evaluation Criteria in Solid Tumors (RECIST) Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 Part A specific: - Participant has a histologically and/or cytologically confirmed diagnosis of one of the following advanced solid tumor types: colorectal adenocarcinoma, esophageal carcinoma, head and neck squamous cell carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, pancreatic adenocarcinoma, prostate adenocarcinoma, stomach adenocarcinoma, bladder urothelial carcinoma, or breast invasive carcinoma Part B and C specific: - Participant has a histologically and/or cytologically confirmed diagnosis of one of the following advanced solid tumor types: colorectal adenocarcinoma, gastric adenocarcinoma, or adenocarcinoma of the gastroesophageal junction Part A1 specific: - Participant has histologically and/or cytologically confirmed diagnosis of one of the following advanced solid tumor types: colorectal adenocarcinoma, gastric adenocarcinoma, adenocarcinoma of the gastroesophageal junction, or pancreatic cancer Exclusion Criteria: Participant has a known hypersensitivity to any components of the study medications or comparable drugs Active and clinically significant bacterial, fungal, or viral infection, known infections with hepatitis B, hepatitis C, known human immunodeficiency virus, or acquired immunodeficiency syndrome related illness Symptomatic central nervous system (CNS) malignancy or metastases. Screening of asymptomatic participants without history of CNS metastases is not required. Participants with asymptomatic CNS lesions should have completed standard therapy for their CNS lesions prior to study enrolment Current hematologic malignancies Prior organ or allogeneic stem-cell transplantation QT interval corrected (QTc) >450 msec Participant has impaired renal function Alanine transaminase or AST are ≥2xULN (if liver metastases are present: ≥5xULN) Participant has moderate or severe cardiovascular disease Current or chronic history of liver disease or known hepatic or biliary abnormalities other than liver metastases

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Modular design, escalation & expansion modules. Depending on emerging data, not all modules may open
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A<br>Study participants assigned this arm will receive UCB6114 as monotherapy in escalating cohorts at pre-specified dose levels. | Drug: ginisortamab<br>* Study participants will receive predefined doses of ginisortamab (UCB6114) administered intravenously at pre-specified time points.<br>* Other names: UCB6114;|
| Experimental: Part A1<br>Study participants will receive predefined doses of UCB6114 as monotherapy administered intravenously at pre-specified time points. | Drug: ginisortamab<br>* Study participants will receive predefined doses of ginisortamab (UCB6114) administered intravenously at pre-specified time points.<br>* Other names: UCB6114;|
| Experimental: Part B<br>Study participants assigned to this arm will receive UCB6114 in escalating cohorts at pre-specified dose levels in combination with trifluridine/tipiracil (TFD/TPI). | Drug: ginisortamab<br>* Study participants will receive predefined doses of ginisortamab (UCB6114) administered intravenously at pre-specified time points.<br>* Other names: UCB6114;Drug: trifluridine/tipiracil<br>* Study participants will receive predefined doses of trifluridine/tipiracil (TFD/TPI) administered as film-coated tablets at pre-specified time points.<br>* Other names: Lonsurf®;|
| Experimental: Part C<br>Study participants assigned to this arm will receive UCB6114 in escalating cohorts at pre-specified dose levels in combination with oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) regimen. | Drug: ginisortamab<br>* Study participants will receive predefined doses of ginisortamab (UCB6114) administered intravenously at pre-specified time points.<br>* Other names: UCB6114;Drug: mFOLFOX6<br>* Study participants will receive predefined doses of oxaliplatin, Leucovorin and 5-fluorouracil as part of the mFOLFOX6 chemotherapy regimen administered as intravenous (iv) infusion at prespecified time points.<br>* Other names: fluorouracil;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose-limiting toxicities (DLTs) | Dose-limiting toxicity is defined as any adverse event at least possibly related to UCB6114, and meeting specified DLT criteria. | From Baseline throughout 28 days (Cycle 1) | 
| Incidence of treatment-emergent adverse events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. | From Baseline through study completion, an average of 12 weeks | 
| Severity of TEAEs | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. | From Baseline through study completion, an average of 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UCB6114 concentration by scheduled assessment and cohort for Part A and A1 | Blood samples will be taken at selected times throughout the study to determine UCB6114 concentration following study drug administration. | From Baseline through study completion, an average of 12 weeks | 
| UCB6114 concentration by scheduled assessment and dose level for Part B and C | Blood samples will be taken at selected times throughout the study to determine UCB6114 concentration following study drug administration. | From Baseline through study completion, an average of 12 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced solid tumors, UCB6114, Phase 1/2