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

Advanced/Metastatic Solid Tumors Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05607498
• Other study ID #: EMB07X101
• Status: Recruiting
• Phase: Phase 1
• Start date: March 1, 2023
• Est. completion date: March 31, 2026

Study information

• Verified date: September 2023
• Source: EpimAb Biotherapeutics (Suzhou)Co., Ltd.
• Contact: Xiaodong Sun
• Phone: +8618512158506
• Email: xdsun[@]epimab.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: March 31, 2026
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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.

2. Male or female, and aged = 18 years

3. 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).

4. 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.

5. 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.

6. ECOG performance status 0 or 1

7. Adequate organ function to participate in the trial.

8. Recovery from adverse events (AEs) related to prior anticancer therapy.

Exclusion Criteria:

1. Prior treatment with any agent targeting ROR1.

2. History of Grade 4 immune-related adverse events (irAEs) or irAEs requiring discontinuation of prior therapies.

3. 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.

4. Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) prior to study treatment.

5. Abuse on alcohol, cannabis-derived products, or other drugs.

Related Conditions & MeSH terms

• Advanced/Metastatic Solid Tumors
• Lymphoma
• Recurrence

Intervention

Drug:
• EMB07
EMB07 is a MAT-Fab bispecific antibody against CD3 and RORI

Locations

Country	Name	City	State
Australia	Peninsula and South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	One Clinical Research	Nedlands	Western Australia
China	Affiliated Hospital of Hebei University	Baoding
China	Cancer Hospital Chinese Academy of Medical Sciences	Beijing
China	The First Affiliated Hospital of Bengbu Medical College	Bengbu
China	Hunan Cancer Hospital	Changsha	Hunan
China	Zhujiang Hospital of Southern Medical University	Guangzhou
China	The Affiliated Tumour Hospital of Harbin Medical University	Harbin
China	Shandong Cancer Hospital	Shandong
China	Tianjin Medical University Cancer Institue & Hospital	Tianjin

Sponsors (1)

Lead Sponsor	Collaborator
EpimAb Biotherapeutics (Suzhou)Co., Ltd.

Countries where clinical trial is conducted

Australia,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of adverse events as assessed by CTCAE V5.0.	Incidence and severity of AE.	Screening up to 30 days after the last dose.
Primary	Incidence of serious adverse events (SAE).	Incidence of SAE.	Screening up to 30 days after the last dose, or beyond 30 days if SAE is confirmed to be treatment related.
Primary	Incidence of dose interruptions.	Incidence of dose interruptions of EMB-07 during treatment as a measure of tolerability.	Screening up to 30 days after the last dose.
Primary	Dose intensity.	Actual amount of drug taken by patients divided by the planned amount.	Screening up to 30 days after the last dose.
Primary	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.	First infusion to the end of cycle 1. (each cycle is 28 days).
Secondary	Overall response rate.	Overall response rate measured by RECIST V1.1, iWCLL-2018, Lugano 2014	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.
Secondary	Area under the serum concentration-time curve (AUC) of EMB-07.	Blood samples for serum PK analysis will be obtained (AUC).	Through treatment until EOT visit, expected average 6 months.
Secondary	Maximum serum concentration (Cmax) of EMB-07.	Blood samples for serum PK analysis will be obtained (Cmax).	Through treatment until EOT visit, expected average 6 months.
Secondary	Trough concentration (Ctrough) of EMB-07.	Blood samples for serum PK analysis will be obtained (Ctrough).	Through treatment until EOT visit, expected average 6 months.
Secondary	Average concentration over a dosing interval (Css, avg) of EMB-07.	Blood samples for serum PK analysis will be obtained (Css,avg).	Through treatment until EOT visit, expected average 6 months.
Secondary	Terminal half-life (T1/2) of EMB-07.	Blood samples for serum PK analysis will be obtained (T1/2).	Through treatment until EOT visit, expected average 6 months.
Secondary	Systemic clearance (CL) of EMB-07.	Blood samples for serum PK analysis will be obtained (CL).	Through treatment until EOT visit, expected average 6 months.
Secondary	Steady state volume of distribution (Vss) of EMB-07.	Blood samples for serum PK analysis will be obtained (Vss).	Through treatment until EOT visit, expected average 6 months.
Secondary	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.	Through treatment discontinuation: an average of 6 months
Secondary	Incidence and titer of anti-drug antibodies stimulated by EMB-07.	Antibodies to EMB-07 will be assessed to evaluate potential immunogenicity.	Up to End of Treatment Follow Up Period (30 days after the last dose)