Advanced Solid Tumors
Conditions
Keywords
Phase I/II, Bispecific antibody, PD-1, LAG-3, EMB-02, Immuno-oncology, dose escalation, cohort expansion, Neoplasms, Neoplasm Metastasis, advanced solid tumor
Brief summary
The primary purpose of this study is to identify the recommended Phase 2 dose(s) (RP2Ds) and schedule assessed to be safe for EMB-02 and to characterize the safety and tolerability of EMB-02 at the RP2Ds. Pharmacokinetics (PK), immunogenicity, and the anti-tumor activity of EMB-02 will also be assessed.
Detailed description
This is a Phase I/II, multi-center, open label, multiple-dose, first in human study, designed to assess safety and tolerability, and to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dos(s)e (RP2D\[s\]) for EMB-02 in patients with advanced solid tumors. Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.
Interventions
BIOLOGICALEMB-02
EMB-02 is a FIT-Ig® bispecific antibody against PD-1 and LAG-3.
Sponsors
Shanghai EpimAb Biotherapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation followed by Cohort Expansion Phase at the RP2D.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Willing and able to provide written informed consent. * Phase I: Patients with histologically or cytologically confirmed locally advanced/metastatic solid tumors and have failed (progressed on, or are intolerant of) standard therapies. Moreover, the disease should be measurable or evaluable per RECIST v1.1 * Phase II Cohort A: Patients with histologically or cytologically confirmed locally advanced/metastatic melanoma, excluding uveal melanoma. \> 1 prior therapy, including prior treatment with PD-1/L1(mandatory) and/or CTLA-4 inhibitors(optional). And the disease is measurable or evaluable per RECIST v1.1 * Archival tumor samples available for retrospective analysis or biopsy will be taken. * ECOG performance status 0 or 1 for phase I, and ≤2 for phase II; life expectancy \> 3 Months * Adequate organ function to participate in the trial. * Recovery from adverse events (AEs) related to prior anticancer therapy. * Highly effective contraception
Exclusion criteria
* Patients who have active autoimmune disease or history of autoimmune disease * History of severe irAE. * History of severe allergic reactions * Use of systemic corticosteroids. * Symptomatic central nervous system metastases. * Patients with cardiac dysfunction * Uncontrolled diabetes mellitus with hemoglobin A1c \> 8% (via medical history) * Prior treatment with a LAG-3 inhibitor * Anticancer therapy or radiation \< 5 half-lives or 4 weeks (whichever is shorter) prior to study treatment; * Prior organ or stem cell/bone marrow transplant. * Concurrent malignancy \< 5 years prior to entry. * Patients with active infections. * Major surgery \< 4 weeks or minor surgery \< 2 weeks prior to study treatment * Live virus vaccines \< 30 days prior to screening * Pregnant or breast-feeding females * Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment * Any other serious underlying medical conditions * 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 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-02 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 first cycle of treatment. | 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. |
| Antitumor activity(Objective Response Rate (ORR) | 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 | Measured by RECIST 1.1, only applicable in Phase II part |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Steady state volume of distribution (Vss) of EMB-02 | 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-02 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-02 will be obtained (PFS). |
| Area under the serum concentration-time curve (AUC) of EMB-02 | Through treatment until EOT visit, expected average 6 months | Blood samples for serum PK analysis will be obtained (AUC). |
| Incidence and titer of anti-drug antibodies stimulated by EMB-02 | Up to End of Treatment Follow Up Period (30 days after the last dose) | Antibodies to EMB-02 will be assessed to evaluate potential immunogenicity. |
| Duration of response of EMB-02 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-02 will be obtained (DOR). |
| Maximum serum concentration (Cmax) of EMB-02 | Through treatment until EOT visit, expected average 6 months | Blood samples for serum PK analysis will be obtained (Cmax) |
| Trough concentration (Ctrough) of EMB-02 | 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-02. | 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-02 | 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-02 | Through treatment until EOT visit, expected average 6 months | Blood samples for serum PK analysis will be obtained (CL). |
Countries
Australia, China, United States
Outcome results
None listed