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

NCT04393298 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: ONC0012019-002598-78
• Study Type: interventional
• Target: 93
• Locations: 2 countries
• Sites: 9

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.

Conditions

Advanced Solid Tumors

Keywords

Advanced solid tumors; UCB6114; Phase 1/2

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With 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 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).

  From Baseline until the End of Study (up to 3.8 years)

• Percentage of Participants Based on Severity of Treatment-emergent Adverse Events

  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.

  From Baseline until the End of Study (up to 3.8 years)

• Number of Participants With Dose-limiting Toxicities (DLTs)

  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).

  From Baseline throughout 28 days (Cycle 1)

Secondary Outcomes (2)

• 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)

• 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)

Study Arms (4)

Part A

EXPERIMENTAL

Study participants assigned this arm will receive UCB6114 as monotherapy in escalating cohorts at pre-specified dose levels.

Drug: ginisortamab

Part A1

EXPERIMENTAL

Study participants will receive predefined doses of UCB6114 as monotherapy administered intravenously at pre-specified time points.

Drug: ginisortamab

Part B

EXPERIMENTAL

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; Drug: trifluridine/tipiracil

Part C

EXPERIMENTAL

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; Drug: mFOLFOX6

Interventions

ginisortamab DRUG

Study participants will receive predefined doses of ginisortamab (UCB6114) administered intravenously at pre-specified time points.

Also known as: UCB6114

Part A; Part A1; Part B; Part C

trifluridine/tipiracil DRUG

Study participants will receive predefined doses of trifluridine/tipiracil (TFD/TPI) administered as film-coated tablets at pre-specified time points.

Also known as: TAS-102, Lonsurf®

Part B

mFOLFOX6 DRUG

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.

Also known as: Calcium folinate, 5-FU, fluorouracil

Part C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UCB Biopharma SRL: lead

Study Sites (9)

Onc001 50414

Los Angeles, California, 90033, United States

Location

Onc001 50470

Charleston, South Carolina, 29425, United States

Location

Onc001 50471

Houston, Texas, 77030, United States

Location

Onc001 40305

Glasgow, United Kingdom

Location

Onc001 40113

London, United Kingdom

Location

Onc001 40304

Manchester, United Kingdom

Location

Onc001 40306

Newcastle upon Tyne, United Kingdom

Location

Onc001 40303

Oxford, United Kingdom

Location

Onc001 40302

Sutton, United Kingdom

Location

Related Publications (1)

• Davies GCG, Dedi N, Jones PS, Kevorkian L, McMillan D, Ottone C, Schulze MED, Scott-Tucker A, Tewari R, West S, Wright M, Rowley TF. Discovery of ginisortamab, a potent and novel anti-gremlin-1 antibody in clinical development for the treatment of cancer. MAbs. 2023 Jan-Dec;15(1):2289681. doi: 10.1080/19420862.2023.2289681. Epub 2023 Dec 12.

  PMID: 38084840 DERIVED

MeSH Terms

Interventions

trifluridine tipiracil drug combination; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

001 844 599 2273

Study Officials

• UCB Cares

  001 844 599 2273

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Modular design, escalation \& expansion modules. Depending on emerging data, not all modules may open

Study Record Dates

• First Submitted: March 3, 2020
• First Posted: May 19, 2020
• Study Start: July 9, 2020
• Primary Completion: April 11, 2024
• Study Completion: April 11, 2024
• Last Updated: May 29, 2025
• Results First Posted: May 29, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data from this study may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.

Locations

GB (6); US (3)