Locally Advanced or Metastatic Solid Tumors
Conditions
Keywords
Phase 1, EMB-15
Brief summary
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.
Detailed description
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).
Interventions
BIOLOGICALEMB-15
EMB-15 is a recombinant humanized bi-specific antibody against ALPP/ALPG and CD3
Sponsors
Shanghai EpimAb Biotherapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. Any prior ALPP/ALPG targeting therapy 2. Has received anticancer therapy, radiotherapy, or investigational drug within \< 5 half-lives or 4 weeks (whichever is shorter) prior to study treatment; 3. Active autoimmune disease or history of autoimmune disease 4. Concurrent malignancy \< 5 years prior to study entry 5. active infection 6. Severe or uncontrolled cardiovascular disease requiring treatment 7. Other severe medical conditions
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| incidence and severity of adverse events as assessed by CTCAE v6.0 and ASTCT. | Screening up to follow-up (30 days after the last dose) | Incidence and severity of AE. |
| Incidence of serious adverse events (SAE) | Screening up to follow-up (30 days after the last dose) | Incidence of SAE. |
| Incidence of dose interruptions | Screening up to follow-up (30 days after the last dose) | Incidence of dose interruptions of EMB-15 during treatment as a measure of tolerability. |
| Dose intensity | Screening up to follow-up (30 days after the last dose) | Actual amount of drug taken by patients divided by the planned amount. |
| The incidence of DLTs during the DLT evaluation period. | First infusion to the end of Cycle 1 (each cycle is 28 days) | The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and are specifically defined in study protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the serum concentration-time curve (AUC) of EMB-15 | 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-15 | Through treatment until EOT visit, expected average 6 months | Blood samples for serum PK analysis will be obtained (Cmax) |
| Trough concentration (Ctrough) of EMB-15 | 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-15 | 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-15 | 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-15 | 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-15 | 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-15 as assessed by RECIST 1.1 | 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 | Preliminary anti-tumor activity of EMB-15 will be obtained (PFS). |
| Duration of response of EMB-15 as assessed by RECIST 1.1 | 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 | Preliminary anti-tumor activity of EMB-15 will be obtained (DOR). |
| Incidence and titer of anti-drug antibodies stimulated by EMB-15 | Up to End of Treatment Follow Up Period (30 days after the last dose) | Antibodies to EMB-15 will be assessed to evaluate potential immunogenicity. |
Countries
China
Contacts
CONTACTXi Yang
Outcome results
None listed