A Study of EMB-02 in Participants With Advanced Solid Tumors

Advanced Solid Tumors Clinical Trial

Official title:

A Phase I/II Trial of EMB-02, a Bi-specific Antibody Against PD-1 and LAG-3, in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04618393
• Other study ID #: EMB02X101
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: March 11, 2021
• Est. completion date: March 21, 2024

Study information

• Verified date: May 2024
• Source: Shanghai EpimAb Biotherapeutics Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 47
• Est. completion date: March 21, 2024
• Est. primary completion date: July 12, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

Biological:
• EMB-02
EMB-02 is a FIT-Ig® bispecific antibody against PD-1 and LAG-3.

Locations

Country	Name	City	State
Australia	Monash Health	Clayton	Victoria
Australia	Peninsula & South Eastern Haematology & Oncology Group (PASO)	Frankston	Victoria
Australia	Southern Medical Day Care Centre	Wollongong	New South Wales
China	Beijing Cancer Hospital	Beijing	Beijing
China	HanDan Central Hospital	Handan	Hebei
China	SuiNing Central Hospital	Suining	Sichuan
China	The first Affiliated Hospital of Xiamen University	Xiamen	Fujian
China	HeNan Provincial People's Hospital	Zhengzhou	Henan
United States	University of Colorado Health Medical Group	Colorado Springs	Colorado
United States	Prisma Health-Upstate	Greenville	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai EpimAb Biotherapeutics Co., Ltd.

Countries where clinical trial is conducted

United States,  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 follow-up (30 days after the last dose)
Primary	Incidence of serious adverse events (SAE)	Incidence of SAE.	Screening up to follow-up (30 days after the last dose)
Primary	Incidence of dose interruptions	Incidence of dose interruptions of EMB-02 during treatment as a measure of tolerability.	Screening up to follow-up (30 days after the last dose)
Primary	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)
Primary	The incidence of DLTs during the first cycle of treatment.	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)
Primary	Antitumor activity(Objective Response Rate (ORR)	Measured by RECIST 1.1, only applicable in Phase II part	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	Area under the serum concentration-time curve (AUC) of EMB-02	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-02	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-02	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-02.	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-02	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-02	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-02	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-02 as assessed by RECIST 1.1	Preliminary anti-tumor activity of EMB-02 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
Secondary	Duration of response of EMB-02 as assessed by RECIST 1.1	Preliminary anti-tumor activity of EMB-02 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-02	Antibodies to EMB-02 will be assessed to evaluate potential immunogenicity.	Up to End of Treatment Follow Up Period (30 days after the last dose)