search
Back to results

First in Human Study of EMB-07 in Locally Advanced/Metastatic Solid Tumors or Relapse/Refractory Lymphoma

Primary Purpose

Advanced/Metastatic Solid Tumors, Relapse/Refractory Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
EMB07
Sponsored by
EpimAb Biotherapeutics (Suzhou)Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced/Metastatic Solid Tumors focused on measuring Phase I, Bispecific antibody, CD3, ROR1, EMB07, Dose escalation, Advanced/Metastatic Solid Tumors, Relapse/Refractory Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures. Male or female, and aged ≥ 18 years Treatment group A: Patients with histologically or cytologically locally advanced unresectable or metastatic solid tumors limiting to triple-negative breast cancer, lung adenocarcinoma, ovarian cancer, pancreatic cancer, colorectal cancer, gastric cancer, prostate cancer, bladder cancer, and uterus cancer. Treatment group B: Patients with histologically or cytologically relapse/refractory lymphoma limiting to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL) and diffuse large B cell lymphoma (DLBCL). Treatment group A: Standard therapies do not exist, or are no longer effective, or are not tolerable or accessible to the patient measurable or evaluable disease per RECIST V1.1. Treatment group B: Presence of at least one two-dimensional measurable lesion confirmed by imaging (CT or MRI) (either lymph nodes lesions with any long diameter > 1.5 cm or extranodal lesions with any long diameter > 1.0 cm); for CLL patients whose baseline imaging evaluation determined that no two-dimensional measurable lesions, their peripheral blood monoclonal B lymphocytes should be ≥ 5.0×109/L. Patients must provide archival tumor samples, or a biopsy will be required if archival tumor sample is not available. Archival tumor sample must be taken ≤ 2 years prior to screening, otherwise a fresh tumor biopsy at screening is required. ECOG performance status 0 or 1 Adequate organ function to participate in the trial. Recovery from adverse events (AEs) related to prior anticancer therapy. Exclusion Criteria: Prior treatment with any agent targeting ROR1. History of Grade 4 immune-related adverse events (irAEs) or irAEs requiring discontinuation of prior therapies. Patient with primary central nervous system (CNS) malignancy or symptomatic CNS metastases. Patients with solid tumors with CNS metastases are eligible if they do not need to receive local radiation treatment at the discretion of investigator or if radiation therapy for CNS metastases is completed ≥ 4 weeks prior to study treatment. Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) prior to study treatment. Abuse on alcohol, cannabis-derived products, or other drugs.

Sites / Locations

  • Peninsula and South Eastern Haematology and Oncology GroupRecruiting
  • One Clinical ResearchRecruiting
  • Hunan Cancer HospitalRecruiting
  • Affiliated Hospital of Hebei UniversityRecruiting
  • Cancer Hospital Chinese Academy of Medical SciencesRecruiting
  • The First Affiliated Hospital of Bengbu Medical CollegeRecruiting
  • Zhujiang Hospital of Southern Medical UniversityRecruiting
  • The Affiliated Tumour Hospital of Harbin Medical UniversityRecruiting
  • Shandong Cancer HospitalRecruiting
  • Tianjin Medical University Cancer Institue & HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

EMB-07-Patients with solid tumor

EMB07-Patients with lymphoma

Arm Description

Patients with solid tumor will receive intravenous infusions of EMB-07 weekly (QW). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is reached or all planned doses are administered.

Patients with lymphoma will receive intravenous infusions of EMB-07 weekly (QW). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is reached or all planned doses are administered.

Outcomes

Primary Outcome Measures

Incidence and severity of adverse events as assessed by CTCAE V5.0.
Incidence and severity of AE.
Incidence of serious adverse events (SAE).
Incidence of SAE.
Incidence of dose interruptions.
Incidence of dose interruptions of EMB-07 during treatment as a measure of tolerability.
Dose intensity.
Actual amount of drug taken by patients divided by the planned amount.
The incidence of DLTs during the first cycle of treatment.
The dose limiting toxicities are based on drug related adverse events and are specifically defined in study protocol.

Secondary Outcome Measures

Overall response rate.
Overall response rate measured by RECIST V1.1, iWCLL-2018, Lugano 2014
Area under the serum concentration-time curve (AUC) of EMB-07.
Blood samples for serum PK analysis will be obtained (AUC).
Maximum serum concentration (Cmax) of EMB-07.
Blood samples for serum PK analysis will be obtained (Cmax).
Trough concentration (Ctrough) of EMB-07.
Blood samples for serum PK analysis will be obtained (Ctrough).
Average concentration over a dosing interval (Css, avg) of EMB-07.
Blood samples for serum PK analysis will be obtained (Css,avg).
Terminal half-life (T1/2) of EMB-07.
Blood samples for serum PK analysis will be obtained (T1/2).
Systemic clearance (CL) of EMB-07.
Blood samples for serum PK analysis will be obtained (CL).
Steady state volume of distribution (Vss) of EMB-07.
Blood samples for serum PK analysis will be obtained (Vss).
Progression free survival (PFS) of EMB-07 as assessed by RECIST 1.1, iWCLL-2018, Lugano 2014
From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months.
Incidence and titer of anti-drug antibodies stimulated by EMB-07.
Antibodies to EMB-07 will be assessed to evaluate potential immunogenicity.

Full Information

First Posted
October 27, 2022
Last Updated
September 21, 2023
Sponsor
EpimAb Biotherapeutics (Suzhou)Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT05607498
Brief Title
First in Human Study of EMB-07 in Locally Advanced/Metastatic Solid Tumors or Relapse/Refractory Lymphoma
Official Title
A First-in-human, Phase I, Open-Label Study of EMB-07, a Bi-specific Antibody Anti-CD3 and Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) in Patients With Locally Advanced/Metastatic Solid Tumors or Relapse/Refractory Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2023 (Actual)
Primary Completion Date
October 31, 2025 (Anticipated)
Study Completion Date
March 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EpimAb Biotherapeutics (Suzhou)Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
For solid tumors and lymphoma, respectively: This study is to evaluate the safety and tolerability of EMB-07 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D). Pharmacokinetics (PK), immunogenicity, and the anti-multiple myeloma activity of EMB-07 will also be assessed.
Detailed Description
This is a phase I, multicenter, open label, dose escalation, first in human study, designed to assess safety and tolerability, and to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose for EMB-07 in patient with locally advanced/metastatic solid tumors or relapse/refractory Lymphoma . Pharmacokinetics, pharmacodynamics, immunogenicity and response will also be assessed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced/Metastatic Solid Tumors, Relapse/Refractory Lymphoma
Keywords
Phase I, Bispecific antibody, CD3, ROR1, EMB07, Dose escalation, Advanced/Metastatic Solid Tumors, Relapse/Refractory Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
EMB-07-Patients with solid tumor
Arm Type
Experimental
Arm Description
Patients with solid tumor will receive intravenous infusions of EMB-07 weekly (QW). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is reached or all planned doses are administered.
Arm Title
EMB07-Patients with lymphoma
Arm Type
Experimental
Arm Description
Patients with lymphoma will receive intravenous infusions of EMB-07 weekly (QW). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is reached or all planned doses are administered.
Intervention Type
Drug
Intervention Name(s)
EMB07
Intervention Description
EMB07 is a MAT-Fab bispecific antibody against CD3 and RORI
Primary Outcome Measure Information:
Title
Incidence and severity of adverse events as assessed by CTCAE V5.0.
Description
Incidence and severity of AE.
Time Frame
Screening up to 30 days after the last dose.
Title
Incidence of serious adverse events (SAE).
Description
Incidence of SAE.
Time Frame
Screening up to 30 days after the last dose, or beyond 30 days if SAE is confirmed to be treatment related.
Title
Incidence of dose interruptions.
Description
Incidence of dose interruptions of EMB-07 during treatment as a measure of tolerability.
Time Frame
Screening up to 30 days after the last dose.
Title
Dose intensity.
Description
Actual amount of drug taken by patients divided by the planned amount.
Time Frame
Screening up to 30 days after the last dose.
Title
The incidence of DLTs during the first cycle of treatment.
Description
The dose limiting toxicities are based on drug related adverse events and are specifically defined in study protocol.
Time Frame
First infusion to the end of cycle 1. (each cycle is 28 days).
Secondary Outcome Measure Information:
Title
Overall response rate.
Description
Overall response rate measured by RECIST V1.1, iWCLL-2018, Lugano 2014
Time Frame
From the date of dosing untill the date of first documented progression or date of death from any casue, whichever case first, expected average 6 months.
Title
Area under the serum concentration-time curve (AUC) of EMB-07.
Description
Blood samples for serum PK analysis will be obtained (AUC).
Time Frame
Through treatment until EOT visit, expected average 6 months.
Title
Maximum serum concentration (Cmax) of EMB-07.
Description
Blood samples for serum PK analysis will be obtained (Cmax).
Time Frame
Through treatment until EOT visit, expected average 6 months.
Title
Trough concentration (Ctrough) of EMB-07.
Description
Blood samples for serum PK analysis will be obtained (Ctrough).
Time Frame
Through treatment until EOT visit, expected average 6 months.
Title
Average concentration over a dosing interval (Css, avg) of EMB-07.
Description
Blood samples for serum PK analysis will be obtained (Css,avg).
Time Frame
Through treatment until EOT visit, expected average 6 months.
Title
Terminal half-life (T1/2) of EMB-07.
Description
Blood samples for serum PK analysis will be obtained (T1/2).
Time Frame
Through treatment until EOT visit, expected average 6 months.
Title
Systemic clearance (CL) of EMB-07.
Description
Blood samples for serum PK analysis will be obtained (CL).
Time Frame
Through treatment until EOT visit, expected average 6 months.
Title
Steady state volume of distribution (Vss) of EMB-07.
Description
Blood samples for serum PK analysis will be obtained (Vss).
Time Frame
Through treatment until EOT visit, expected average 6 months.
Title
Progression free survival (PFS) of EMB-07 as assessed by RECIST 1.1, iWCLL-2018, Lugano 2014
Description
From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months.
Time Frame
Through treatment discontinuation: an average of 6 months
Title
Incidence and titer of anti-drug antibodies stimulated by EMB-07.
Description
Antibodies to EMB-07 will be assessed to evaluate potential immunogenicity.
Time Frame
Up to End of Treatment Follow Up Period (30 days after the last dose)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures. Male or female, and aged ≥ 18 years Treatment group A: Patients with histologically or cytologically locally advanced unresectable or metastatic solid tumors limiting to triple-negative breast cancer, lung adenocarcinoma, ovarian cancer, pancreatic cancer, colorectal cancer, gastric cancer, prostate cancer, bladder cancer, and uterus cancer. Treatment group B: Patients with histologically or cytologically relapse/refractory lymphoma limiting to chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL) and diffuse large B cell lymphoma (DLBCL). Treatment group A: Standard therapies do not exist, or are no longer effective, or are not tolerable or accessible to the patient measurable or evaluable disease per RECIST V1.1. Treatment group B: Presence of at least one two-dimensional measurable lesion confirmed by imaging (CT or MRI) (either lymph nodes lesions with any long diameter > 1.5 cm or extranodal lesions with any long diameter > 1.0 cm); for CLL patients whose baseline imaging evaluation determined that no two-dimensional measurable lesions, their peripheral blood monoclonal B lymphocytes should be ≥ 5.0×109/L. Patients must provide archival tumor samples, or a biopsy will be required if archival tumor sample is not available. Archival tumor sample must be taken ≤ 2 years prior to screening, otherwise a fresh tumor biopsy at screening is required. ECOG performance status 0 or 1 Adequate organ function to participate in the trial. Recovery from adverse events (AEs) related to prior anticancer therapy. Exclusion Criteria: Prior treatment with any agent targeting ROR1. History of Grade 4 immune-related adverse events (irAEs) or irAEs requiring discontinuation of prior therapies. Patient with primary central nervous system (CNS) malignancy or symptomatic CNS metastases. Patients with solid tumors with CNS metastases are eligible if they do not need to receive local radiation treatment at the discretion of investigator or if radiation therapy for CNS metastases is completed ≥ 4 weeks prior to study treatment. Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) prior to study treatment. Abuse on alcohol, cannabis-derived products, or other drugs.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xiaodong Sun
Phone
+8618512158506
Email
xdsun@epimab.com
First Name & Middle Initial & Last Name or Official Title & Degree
Xuemei Xie
Phone
+8615721294395
Email
xmxie@epimab.com
Facility Information:
Facility Name
Peninsula and South Eastern Haematology and Oncology Group
City
Frankston
State/Province
Victoria
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ganju
Facility Name
One Clinical Research
City
Nedlands
State/Province
Western Australia
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ariyapperuma
Facility Name
Hunan Cancer Hospital
City
Changsha
State/Province
Hunan
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Quchang Ouyang
Facility Name
Affiliated Hospital of Hebei University
City
Baoding
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Youchao Jia
Facility Name
Cancer Hospital Chinese Academy of Medical Sciences
City
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yuankai Shi
Facility Name
The First Affiliated Hospital of Bengbu Medical College
City
Bengbu
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yanli Yang
First Name & Middle Initial & Last Name & Degree
Huan Zhou
Facility Name
Zhujiang Hospital of Southern Medical University
City
Guangzhou
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sanfang Tu
Facility Name
The Affiliated Tumour Hospital of Harbin Medical University
City
Harbin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qingyuan Zhang
Facility Name
Shandong Cancer Hospital
City
Shandong
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zengjun Li
First Name & Middle Initial & Last Name & Degree
Yuping Sun
Facility Name
Tianjin Medical University Cancer Institue & Hospital
City
Tianjin
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lanfang Li

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

First in Human Study of EMB-07 in Locally Advanced/Metastatic Solid Tumors or Relapse/Refractory Lymphoma

We'll reach out to this number within 24 hrs