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

Overview

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.

Interventions

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

Primary outcome measures

• Incidence and severity of adverse events as assessed by CTCAE V5.0. [Time frame: Screening up to 30 days after the last dose.]
• 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 dose interruptions. [Time frame: Screening up to 30 days after the last dose.]
• Dose intensity. [Time frame: Screening up to 30 days after the last dose.]
• 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).]

Secondary outcome measures (10)

• 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.]
• Area under the serum concentration-time curve (AUC) of EMB-07. [Time frame: Through treatment until EOT visit, expected average 6 months.]
• Maximum serum concentration (Cmax) of EMB-07. [Time frame: Through treatment until EOT visit, expected average 6 months.]
• Trough concentration (Ctrough) of EMB-07. [Time frame: Through treatment until EOT visit, expected average 6 months.]
• Average concentration over a dosing interval (Css, avg) of EMB-07. [Time frame: Through treatment until EOT visit, expected average 6 months.]
• Terminal half-life (T1/2) of EMB-07. [Time frame: Through treatment until EOT visit, expected average 6 months.]
• Systemic clearance (CL) of EMB-07. [Time frame: Through treatment until EOT visit, expected average 6 months.]
• Steady state volume of distribution (Vss) of EMB-07. [Time frame: Through treatment until EOT visit, expected average 6 months.]
• 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]
• 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)]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 8 centers

• Hunan Cancer Hospital — Changsha
• Affiliated Hospital of Hebei University — Baoding
• Cancer Hospital Chinese Academy of Medical Sciences — Beijing
• The First Affiliated Hospital of Bengbu Medical College — Bengbu
• Zhujiang Hospital of Southern Medical University — Guangzhou
• The Affiliated Tumour Hospital of Harbin Medical University — Harbin
• Shandong Cancer Hospital — Shandong
• Tianjin Medical University Cancer Institue & Hospital — Tianjin

Australia · 2 centers

• Peninsula and South Eastern Haematology and Oncology Group — Frankston
• One Clinical Research — Nedlands

Identifiers

NCT: NCT05607498 · EMB07X101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗