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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05263180
• Other study ID #: EMB09X101
• Status: Recruiting
• Phase: Phase 1
• Start date: July 25, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: October 2023
• Source: Shanghai EpimAb Biotherapeutics Co., Ltd.
• Contact: Shuqi Zeng, MD.
• Phone: +86-21-61043299
• Email: shqzeng[@]epimab.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

1. 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).

2. Patients who have failed (progressed on, or are intolerant of) standard therapies or no available standard treatment

3. 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Neoplasms

Intervention

Biological:
• EMB-09
EMB-09 is a FIT-Ig® bispecific antibody against PD-L1 and OX40.

Locations

Country	Name	City	State
Australia	Peninsula and South Eastern Haematology & Oncology Group	Frankston
Australia	GenesisCareNorthShore	Leonards Hill
Australia	Blacktown Hospital	Sydney
China	FUSCC	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai EpimAb Biotherapeutics Co., Ltd.

Countries where clinical trial is conducted

Australia,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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.
Primary	Dose intensity.	Actual amount of drug taken by patients divided by the planned amount.	Screening up to 30 days after the last dose.
Primary	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	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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