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

Sponsor

Shanghai EpimAb Biotherapeutics Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04618393

Collaborator

(none)

Enrollment

Locations

Arm

57.7

Anticipated Duration (Months)

7.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Biological: EMB-02	Phase 1/Phase 2

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 dose (RP2D) for EMB-02 in patients with advanced solid tumors. Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

43 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Dose escalation followed by Cohort Expansion Phase at the RP2D.Dose escalation followed by Cohort Expansion Phase at the RP2D.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Mar 11, 2021

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EMB-02 In Phase I part: participants enrolled in the different time will receive EMB-02 once weekly (IV) at different ascending dose levels. In Phase II part: participants will receive EMB-02 once weekly (IV) at previously defined RP2D.	Biological: EMB-02 EMB-02 is a FIT-Ig® bispecific antibody against PD-1 and LAG-3.

Arm

Intervention/Treatment

Experimental: EMB-02

In Phase I part: participants enrolled in the different time will receive EMB-02 once weekly (IV) at different ascending dose levels. In Phase II part: participants will receive EMB-02 once weekly (IV) at previously defined RP2D.

Biological: EMB-02

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

Outcome Measures

Primary Outcome Measures

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.
Overall 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 Outcome Measures

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).
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).
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).
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).
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Health Medical Group	Colorado Springs	Colorado	United States	80909
2	Prisma Health-Upstate	Greenville	South Carolina	United States	29605
3	Southern Medical Day Care Centre	Wollongong	New South Wales	Australia	2500
4	Monash Health	Clayton	Victoria	Australia	3168
5	Peninsula & South Eastern Haematology & Oncology Group (PASO)	Frankston	Victoria	Australia	3199
6	Beijing Cancer Hospital	Beijing	Beijing	China	100000