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The primary purpose of this study is to evaluate safety and tolerability profile of EMB-15, identify the recommended Phase 2 dose(s) (RP2Ds) for EMB-15. Pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and the anti-tumor activity of EMB-15 will also be assessed.
This is a first-in-human (FIH), open-label, Phase I, multicenter dose escalation study to identify the RP2D and to evaluate the safety, tolerability, pharmacokinetics, and antitumor activities of EMB-15 in adult patients with locally advanced/metastatic solid tumors who have progressed on available standard of care or for which no standard therapy exists.This is an open-label, non-randomized dose-escalation study comprising a dose-escalation phase and a dose-expansion phase. It's planned to recruit approximately 50 patients (the final number will be determined depending on the number of dose levels) with locally advanced or metastatic solid tumors. The trial consists of a screening period (Day -28 to Day -1), a step-up dose period (applicable only to doses with higher CRS risk, lasting 7 days or longer), a treatment period (28 days per cycle, up to 2 years), and a safety follow-up period (30 days after the last dose).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EMB-15 | Experimental | This is an open-label, non-randomized dose-escalation study comprising a dose-escalation phase and a dose-expansion phase. It's planned to recruit approximately 50 patients (the final number will be determined depending on the number of dose levels) with locally advanced or metastatic solid tumors. The trial consists of a screening period (Day -28 to Day -1), a step-up dose period (applicable only to doses with higher CRS risk, lasting 7 days or longer), a treatment period (28 days per cycle, up to 2 years), and a safety follow-up period (30 days after the last dose). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EMB-15 | Biological | EMB-15 is a recombinant humanized bi-specific antibody against ALPP/ALPG and CD3 |
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| Measure | Description | Time Frame |
|---|---|---|
| incidence and severity of adverse events as assessed by CTCAE v6.0 and ASTCT. | Incidence and severity of AE. | Screening up to follow-up (30 days after the last dose) |
| Incidence of serious adverse events (SAE) | Incidence of SAE. | Screening up to follow-up (30 days after the last dose) |
| Incidence of dose interruptions | Incidence of dose interruptions of EMB-15 during treatment as a measure of tolerability. | Screening up to follow-up (30 days after the last dose) |
| Dose intensity | Actual amount of drug taken by patients divided by the planned amount. | Screening up to follow-up (30 days after the last dose) |
| The incidence of DLTs during the DLT evaluation period. | The Dose Limiting Toxicities (DLTs) 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the serum concentration-time curve (AUC) of EMB-15 | Blood samples for serum PK analysis will be obtained (AUC). | Through treatment until EOT visit, expected average 6 months |
| Maximum serum concentration (Cmax) of EMB-15 |
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Inclusion Criteria:
- 1) Able to understand and willing to sign an ICF 2) Males or females with the age ≥ 18 years 3) Life expectancy > 3 months. 4) ECOG performance status 0 or 1 5) Patients must have histologically or cytologically confirmed locally advanced or metastatic solid tumors, without standard therapy.
6) Patients must provide archived tumor samples collected within 1 year. 7) Adequate hematological and organ function.
Exclusion Criteria:
Patients meeting any of the following criteria will not be enrolled:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Xi Yang | Contact | 86-21-61951000 | xyang@epimab.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sixth Affiliated Hospital of Sun Yat-sen University | Recruiting | Guangzhou | Guangdong | 510655 | China |
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Blood samples for serum PK analysis will be obtained (Cmax)
| Through treatment until EOT visit, expected average 6 months |
| Trough concentration (Ctrough) of EMB-15 | Blood samples for serum PK analysis will be obtained (Ctrough) | Through treatment until EOT visit, expected average 6 months |
| Average concentration over a dosing interval (Css, avg)of EMB-15 | Blood samples for serum PK analysis will be obtained (Css, avg). | Through treatment until EOT visit, expected average 6 months |
| Terminal half-life (T1/2) of EMB-15 | Blood samples for serum PK analysis will be obtained (T1/2) | Through treatment until EOT visit, expected average 6 months. |
| Systemic clearance (CL) of EMB-15 | Blood samples for serum PK analysis will be obtained (CL). | Through treatment until EOT visit, expected average 6 months. |
| Steady state volume of distribution (Vss) of EMB-15 | Blood samples for serum PK analysis will be obtained (Vss). | Through treatment until EOT visit, expected average 6 months |
| Progression free survival (PFS) of EMB-15 as assessed by RECIST 1.1 | Preliminary anti-tumor activity of EMB-15 will be obtained (PFS). | 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 |
| Duration of response of EMB-15 as assessed by RECIST 1.1 | Preliminary anti-tumor activity of EMB-15 will be obtained (DOR). | 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-15 | Antibodies to EMB-15 will be assessed to evaluate potential immunogenicity. | Up to End of Treatment Follow Up Period (30 days after the last dose) |