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

• ClinicalTrials.gov Identifier: NCT05607498
• Recruitment Status: Recruiting
• First Posted: November 7, 2022
• Last Update Posted: September 22, 2023
• Sponsor: EpimAb Biotherapeutics (Suzhou)Co., Ltd.
• Information provided by (Responsible Party): EpimAb Biotherapeutics (Suzhou)Co., Ltd.

Tracking Information

• First Submitted Date: October 27, 2022
• First Posted Date: November 7, 2022
• Last Update Posted Date: September 22, 2023
• Actual Study Start Date: March 1, 2023
• Estimated Primary Completion Date: October 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 3, 2022)

• Incidence and severity of adverse events as assessed by CTCAE V5.0. [ Time Frame: Screening up to 30 days after the last dose. ]
  Incidence and severity of AE.
• Incidence of serious adverse events (SAE). [ Time Frame: Screening up to 30 days after the last dose, or beyond 30 days if SAE is confirmed to be treatment related. ]
  Incidence of SAE.
• Incidence of dose interruptions. [ Time Frame: Screening up to 30 days after the last dose. ]
  Incidence of dose interruptions of EMB-07 during treatment as a measure of tolerability.
• Dose intensity. [ Time Frame: Screening up to 30 days after the last dose. ]
  Actual amount of drug taken by patients divided by the planned amount.
• The incidence of DLTs during the first cycle of treatment. [ Time Frame: First infusion to the end of cycle 1. (each cycle is 28 days). ]
  The dose limiting toxicities are based on drug related adverse events and are specifically defined in study protocol.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: September 21, 2023)

• Overall response rate. [ 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. ]
  Overall response rate measured by RECIST V1.1, iWCLL-2018, Lugano 2014
• Area under the serum concentration-time curve (AUC) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (AUC).
• Maximum serum concentration (Cmax) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (Cmax).
• Trough concentration (Ctrough) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (Ctrough).
• Average concentration over a dosing interval (Css, avg) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (Css,avg).
• Terminal half-life (T1/2) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (T1/2).
• Systemic clearance (CL) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (CL).
• Steady state volume of distribution (Vss) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  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 [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  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. [ Time Frame: Up to End of Treatment Follow Up Period (30 days after the last dose) ]
  Antibodies to EMB-07 will be assessed to evaluate potential immunogenicity.

Original Secondary Outcome Measures (submitted: November 3, 2022)

• Overall response rate. [ 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. ]
  Overall response rate measured by RECIST V1.1.
• Area under the serum concentration-time curve (AUC) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (AUC).
• Maximum serum concentration (Cmax) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (Cmax).
• Trough concentration (Ctrough) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (Ctrough).
• Average concentration over a dosing interval (Css, avg) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (Css,avg).
• Terminal half-life (T1/2) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (T1/2).
• Systemic clearance (CL) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (CL).
• Steady state volume of distribution (Vss) of EMB-07. [ Time Frame: Through treatment until EOT visit, expected average 6 months. ]
  Blood samples for serum PK analysis will be obtained (Vss).
• Progression free survival (PFS) of EMB-07 as assessed by RECIST 1.1. [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  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. [ Time Frame: Up to End of Treatment Follow Up Period (30 days after the last dose) ]
  Antibodies to EMB-07 will be assessed to evaluate potential immunogenicity.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Advanced/Metastatic Solid Tumors
• Relapse/Refractory Lymphoma

Intervention

Drug: EMB07

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

Study Arms

• Experimental: EMB-07-Patients with solid tumor
  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.
  Intervention: Drug: EMB07
• Experimental: EMB07-Patients with lymphoma
  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: Drug: EMB07

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: September 21, 2023): 150
• Original Estimated Enrollment (submitted: November 3, 2022): 75
• Estimated Study Completion Date: March 31, 2026
• Estimated Primary Completion Date: October 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Xiaodong Sun; +8618512158506; xdsun@epimab.com

Contact: Xuemei Xie; +8615721294395; xmxie@epimab.com

• Listed Location Countries: Australia, China

Administrative Information

• NCT Number: NCT05607498
• Other Study ID Numbers: EMB07X101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: EpimAb Biotherapeutics (Suzhou)Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: EpimAb Biotherapeutics (Suzhou)Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: EpimAb Biotherapeutics (Suzhou)Co., Ltd.
• Verification Date: September 2023