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

NCT04618393 | Terminated Phase 1 FDA Drug

• 1 other identifier: EMB02X101
• Study Type: interventional
• Target: 47
• Locations: 3 countries
• Sites: 10

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.

Conditions

Advanced Solid Tumors

Keywords

Phase I/II; Bispecific antibody; PD-1; LAG-3; EMB-02; Immuno-oncology; dose escalation; cohort expansion; Neoplasms; Neoplasm Metastasis; advanced solid tumor

Outcome Measures

Primary Outcomes (6)

• 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)

• Incidence of serious adverse events (SAE)

  Incidence of SAE.

  Screening up to follow-up (30 days after the last dose)

• 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)

• 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)

• 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)

• 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 Outcomes (10)

• Area under the serum concentration-time curve (AUC) of EMB-02

  Through treatment until EOT visit, expected average 6 months

• Maximum serum concentration (Cmax) of EMB-02

  Through treatment until EOT visit, expected average 6 months

• Trough concentration (Ctrough) of EMB-02

  Through treatment until EOT visit, expected average 6 months

• Average concentration over a dosing interval (Css, avg)of EMB-02.

  Through treatment until EOT visit, expected average 6 months

• Terminal half-life (T1/2) of EMB-02

  Through treatment until EOT visit, expected average 6 months.

Study Arms (1)

EMB-02

EXPERIMENTAL

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

Interventions

EMB-02 BIOLOGICAL

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

EMB-02

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai EpimAb Biotherapeutics Co., Ltd.: lead

Study Sites (10)

University of Colorado Health Medical Group

Colorado Springs, Colorado, 80909, United States

Location

Prisma Health-Upstate

Greenville, South Carolina, 29605, United States

Location

Southern Medical Day Care Centre

Wollongong, New South Wales, 2500, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Peninsula & South Eastern Haematology & Oncology Group (PASO)

Frankston, Victoria, 3199, Australia

Location

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100000, China

Location

The first Affiliated Hospital of Xiamen University

Xiamen, Fujian, China

Location

HanDan Central Hospital

Handan, Hebei, China

Location

HeNan Provincial People's Hospital

Zhengzhou, Henan, China

Location

SuiNing Central Hospital

Suining, Sichuan, China

Location

Related Publications (2)

• Day D, Ganju V, Chung K, Si L, Mao L, Aghmesheh M, Hoyer R, Brewin K, Zeng S, Zhang M, Lu Q, Jiang C, Ren F, Zhu Y, Guo J. First-in-human phase I study of EMB-02, a bispecific antibody targeting PD-1 and LAG-3 in patients with advanced solid tumors. Br J Cancer. 2025 Jun;132(10):905-912. doi: 10.1038/s41416-025-02990-x. Epub 2025 Apr 15.

  PMID: 40234667 DERIVED

• Jiang C, Ren F, Zhang M, Lu Q, Zeng S, Yang G, Zhu Y. Using Pharmacokinetic and Pharmacodynamic Analysis to Optimize the Dosing Regimens of Fanastomig (EMB-02) in Patients With Advanced Solid Tumors. CPT Pharmacometrics Syst Pharmacol. 2025 May;14(5):975-986. doi: 10.1002/psp4.70011. Epub 2025 Mar 11.

  PMID: 40067130 DERIVED

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose escalation followed by Cohort Expansion Phase at the RP2D.

Study Record Dates

• First Submitted: October 18, 2020
• First Posted: November 5, 2020
• Study Start: March 11, 2021
• Primary Completion: July 12, 2023
• Study Completion: March 21, 2024
• Last Updated: May 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5); US (2); AU (3)