Advanced/Metastatic Solid Tumors, Relapse/Refractory Lymphoma
Conditions
Keywords
Phase I, Bispecific antibody, CD3, ROR1, EMB07, Dose escalation, Advanced/Metastatic Solid Tumors, 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.
Interventions
DRUGEMB07
EMB07 is a MAT-Fab bispecific antibody against CD3 and RORI
Sponsors
EpimAb Biotherapeutics (Suzhou)Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events as assessed by CTCAE V5.0. | Screening up to 30 days after the last dose. | Incidence and severity of AE. |
| Incidence of serious adverse events (SAE). | 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. | 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. | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal half-life (T1/2) of EMB-07. | 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. | Through treatment until EOT visit, expected average 6 months. | Blood samples for serum PK analysis will be obtained (CL). |
| Overall response rate. | 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 |
| Progression free survival (PFS) of EMB-07 as assessed by RECIST 1.1, iWCLL-2018, Lugano 2014 | 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. | 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. |
| Steady state volume of distribution (Vss) of EMB-07. | Through treatment until EOT visit, expected average 6 months. | Blood samples for serum PK analysis will be obtained (Vss). |
| Area under the serum concentration-time curve (AUC) of EMB-07. | 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. | 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. | 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. | Through treatment until EOT visit, expected average 6 months. | Blood samples for serum PK analysis will be obtained (Css,avg). |
Countries
Australia, China
Contacts
Primary ContactSai Lou
Backup ContactJunqiang He
Outcome results
None listed