A Study to Assess the Safety, Pharmacokinetics and Anti Tumor Activity of UCB6114 Administered Intravenously to Participants With Advanced Solid Tumors
- Conditions
- Advanced Solid Tumors
- Interventions
- Registration Number
- NCT04393298
- Lead Sponsor
- UCB Biopharma SRL
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 93
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part B trifluridine/tipiracil Study participants assigned to this arm will receive UCB6114 in escalating cohorts at pre-specified dose levels in combination with trifluridine/tipiracil (TFD/TPI). Part C mFOLFOX6 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. Part A ginisortamab Study participants assigned this arm will receive UCB6114 as monotherapy in escalating cohorts at pre-specified dose levels. Part B ginisortamab Study participants assigned to this arm will receive UCB6114 in escalating cohorts at pre-specified dose levels in combination with trifluridine/tipiracil (TFD/TPI). Part C ginisortamab 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. Part A1 ginisortamab Study participants will receive predefined doses of UCB6114 as monotherapy administered intravenously at pre-specified time points.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From Baseline until the End of Study (up to 3.8 years) An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. 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 study medication. A treatment-emergent adverse event (TEAE) was defined as any AE with a start date on or after the first dose of UCB6114 up until the last dose of Ginisortamab (UCB6114) +30 days (i.e. up to 3.8 years).
Percentage of Participants Based on Severity of Treatment-emergent Adverse Events From Baseline until the End of Study (up to 3.8 years) AE is any untoward medical occurrence in patient or clinical study participant, temporally associated with use of study medication, whether or not considered related to study medication. AE can therefore be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of study medication. TEAE: any AE with start date on or after first dose of UCB6114 up until last dose of Ginisortamab(UCB6114)+30 days. Event for which no Common Terminology Criteria for AE (CTCAE) severity grade was recorded by investigator but intensity was recorded instead was assigned as follows to CTCAE severity grade:Severe=Grade 3, Life Threatening (indicated on electronic case report form (eCRF) for event that is serious)=Grade 4, Death (indicated on the eCRF for event that is serious or has outcome of death)=Grade 5. As planned, data reported for National Cancer Institute (NCI) CTCAE grade \>=3 TEAEs and related TEAEs.
Number of Participants With Dose-limiting Toxicities (DLTs) From Baseline throughout 28 days (Cycle 1) DLT defined as any AE at least related to study medication that occurs during Cycle 1 and met following criteria: Grade (Gr) 3 or 4 nonhematological toxicity according to NCI CTCAE (Version 5.0) except for alopecia, or nausea, vomiting, or diarrhea that reverses to Gr ≤2 within 24 hours (hr) with appropriate medical therapy; Gr 3 or 4 biochemical abnormality that persists despite maximal supportive treatment or biochemical abnormalities that is symptomatic and nontransient; Any Gr ≥3 hematological toxicity of \>5 days duration or febrile neutropenia (absolute neutrophil count \[ANC\]\<1000/cubic millimeter\[mm3\] with single temperature of \>38.3°C or sustained temperature ≥38°C for more than one hr), infection with Gr 3 or 4 neutropenia, thrombocytopenia with bleeding or requiring platelet transfusion, or Gr 4 thrombocytopenia; Prolonged Gr 2 diarrhea (\>7 days) despite adequate antidiarrheal medication, or multiple Grade 1or 2 toxicities(eg, Gr 1 or 2 diarrhea, vomiting, rash, and fatigue).
- Secondary Outcome Measures
Name Time Method Part A and A1: UCB6114 Serum Concentration by Scheduled Assessment and Cohort Parts A: Cycle 1 (Day 1 end of infusion [EOI] and Day 15 Predose), Cycle 2 (Day 1 Predose and Day 15 Predose); Part A 1: Cycle 1 (Day 1 EOI and Day 15 Predose), Cycle 2 (Day 1 Predose) Blood samples for ginisortamab serum concentration analysis were collected at different timepoints following the first dose of ginisortamab. The data is reported for Part A and A1. Pharmacokinetic Set (PKS). Lower Limit of Quantitation (LLOQ).
Part B and C: UCB6114 Concentration by Scheduled Assessment and Dose Level Part B and C: Cycle 1 (Day 1 EOI and Day 15 Predose), Cycle 2 (Day 1 Predose and Day 15 Predose) Blood samples for ginisortamab serum concentration analysis were collected at timepoints following (Cycle 1 Day 1) and the (Cycle 2 Day 1) administration of ginisortamab. Data is reported for Part B and Part C.
Trial Locations
- Locations (9)
Onc001 50414
🇺🇸Los Angeles, California, United States
Onc001 50470
🇺🇸Charleston, South Carolina, United States
Onc001 50471
🇺🇸Houston, Texas, United States
Onc001 40305
🇬🇧Glasgow, United Kingdom
Onc001 40113
🇬🇧London, United Kingdom
Onc001 40304
🇬🇧Manchester, United Kingdom
Onc001 40306
🇬🇧Newcastle Upon Tyne, United Kingdom
Onc001 40303
🇬🇧Oxford, United Kingdom
Onc001 40302
🇬🇧Sutton, United Kingdom
Onc001 50414🇺🇸Los Angeles, California, United States