A Study of EMB-09 in Participants With Advanced or Metastatic Solid Tumors.

Study Overview
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Brief Summary
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This study is to evaluate the safety and tolerability of EMB-09 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-09 will also be assessed.

Detailed Description
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This is a phase I, 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 dose for EMB-09 in patient with advanced or metastatic solid tumors. Pharmacokinetics,pharmacodynamics, immunogenicity and response will also be assessed.

Official Title
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A First-in-human, Phase I Trial of EMB-09, a Bispecific Antibody Targeting PD-L1 and OX-40 in Patients With Advanced or Metastatic Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Biological: EMB-09


Participation Criteria
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Eligibility Criteria
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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. Phase I subjects: Patients with histologically or cytologically confirmed locally advanced/metastatic solid tumors including but not limited to melanoma, non-small cell lung cancer (NSCLC), triple negative breast cancer (TNBC), head and neck squamous cell carcinoma (HNSCC), nasopharyngeal cancer (NPC), hepatocellular carcinoma (HCC), gastric cancer (GC), endometrium cancer (EC), ovarian cancer (OC), renal cell carcinoma (RCC) and small cell lung cancer (SCLC), colorectal cancer (CRC). Patients who have failed (progressed on, or are intolerant of) standard therapies or no available standard treatment Measurable or evaluable disease per RECIST v1.1. Patients must provide archival tumor, or a fresh tumor 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; 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 TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR), CD40. Anticancer therapy or radiation < 5 half-lives or 4 weeks (whichever is shorter) prior to study treatment; Current or history of idiopathic pulmonary fibrosis, interstitial lung disease, or organizing pneumonia. 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 of alcohol, cannabis-derived products, or other drugs.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group Assignment Dose escalation followed by Cohort Expansion Phase at the RP2D.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: EMB-09<br>Participants enrolled at different time will receive EMB-09 once a week (IV) at different ascending dose levels. | Biological: EMB-09<br>* EMB-09 is a FIT-Ig® bispecific antibody against PD-L1 and OX40.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events as assessed by CTCAE V5.0 | Incidence and severity of AE. | Screening up to 30 days after the last dose. | 
| Incidence of serious adverse events. (SAE) | Incidence of SAE. | 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. | Incidence of dose interruptions of EMB-09 during treatment as a measure of tolerability. | Screening up to 30 days after the las dose. | 
| Dose intensity. | Actual amount of drug taken by patients divided by the planned amount. | Screening up to 30 days after the last dose. | 
| The incidence of DLTs during the first cycle of treatment. | The dose limiting toxicities 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Measured by RECIST 1.1. | From the date of dosing until the date of first documented progression or date of death from any cause, whichever case first, expected average 6 months. | 
| Area under the serum concentration-time curve (AUC) of EMB-09 | 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-09 | Blood samples for serum PK analysis will be obtained (Cmax) | Through treatment until EOT visit, expected average 6 months | 
| Trough concentration (Ctrough) of EMB-09 | 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-09. | 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-09 | 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-09 | 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-09 | 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-09 as assessed by RECIST 1 | Preliminary anti-tumor activity of EMB-09 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-09 | Antibodies to EMB-09 will be assessed to evaluate potential immunogenicity. | Up to End of Treatment Follow Up Period (30 days after the last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, Bispecific antibody, OX40, PD-L1, EMB-09, Immuno-oncology, dose escalation, cohort expansion, advanced solid tumor