A Dose Escalation With Expansion Study of EMB-01 in Participants With Advanced/Metastatic Solid Tumors

Neoplasms Clinical Trial

Official title:

First-in-human, Phase I/II, Multicenter, Open-Label Study of EMB-01 in Patients With Advanced/Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03797391
• Other study ID #: EMB01X101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 13, 2018
• Est. completion date: January 15, 2026

Study information

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

Clinical Trial Summary

First-in-human, Phase I/II, Multicenter, Open-Label Study of EMB-01 in Patients with Advanced/Metastatic Solid Tumors

Description:

This is a first-in-human (FIH), open-label, Phase I/II study of EMB-01, a bispecific Epidermal growth factor receptor (EGFR) and c-Mesenchymal-Epithelial Transition (cMet) antibody, in patients with advanced solid tumors who have progressed on available standard therapies or for which no standard therapy exists. The study consists of two parts: Phase I (dose escalation) and Phase II (cohort expansion). The study is planning to recruit tentatively 33-66 subjects with advanced/metastatic solid tumors in phase I and approximately 42-120 subjects with EGFR mutant and/or cMET aberrated NSCLC who have progressed on or are intolerant to standard treatment(s) (including platinum-based therapy) will be enrolled at the RP2D(s) in phase II part of the study. In phase II, patients will be assigned to five groups according to their molecular status at baseline. The trial will consist of molecular pre-screening period (Phase II only), clinical screening period (-28 to -1 days), treatment cycles (each cycle is 28 days, maximum up to 2 years), and safety follow-up period (30 days after the last dose).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 186
• Est. completion date: January 15, 2026
• Est. primary completion date: March 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

Molecular Pre-screening Inclusion criteria (Phase II only)

1. The patient must sign the molecular pre-screening Inform Consent to allow for the molecular pre-screening process. All patients must have documented evidence of EGFR and/or cMet aberrations.

Screening Inclusion Criteria

1. Able to understand and willing to sign the Informed Consent Form (ICF).

2. Histologically/cytologically confirmed advanced/metastatic solid tumors with measurable disease [Response Evaluation Criteria in Solid Tumors (RECIST) v1.1]:

Phase I: advanced/metastatic solid tumors including but not limited to NSCLC, colorectal cancer, gastric cancer and liver cancer refractory to standard therapy or for which no standard therapy is available or accessible.

Phase II: Advanced/metastatic NSCLC Patients have confirmed EGFR mutant and/or cMET aberration, and have progressed after standard treatment (including platinum-based therapy) or are intolerant to standard treatment. Additionally, patients with T790M mutation have received FDA/Health Authority approved therapies (if accessible) for this indication (i.e., osimertinib) and have progressed or became intolerant.

A patient who has refused all currently available therapy is allowed to enroll, but must be documented in the source record.

3. Must have adequate organ function.

4. Regarding prior anti-tumor therapy:

1. Must have stopped treatment at least 4 weeks or within 5 half-lives.

2. Generalized radiation therapy must have stopped 3 weeks before first dose of EMB 01, or local radiotherapy or radiation therapy for bone metastases must have stopped 2 weeks before first dose of EMB-01. No therapeutic radiopharmaceuticals are taken within 8 weeks before first dose of EMB-01.

3. Patients must have recovered to =Grade 1 from the adverse effects of such above treatment before beginning study treatment.

5. Female patient with fertility or male patient whose partner has fertility should use one or more contraceptive methods for contraception starting from screening period and continue throughout the study treatment and for 3 months.

6. ECOG score 0 or 1 for phase I, and =2 for phase II.

Exclusion Criteria:

Molecular Pre-screening Exclusion Criteria (Phase II only)

Subject who meets any of the follow criteria can't be proceeded to clinical screening:

1. Patients who are unwilling to sign the molecular pre-screening ICF.

2. Patients for whom local EGFR and/or cMET data or the results of central laboratory testing do not meet the molecular pre-screening inclusion criteria.

Screening Exclusion Criteria

1. Life expectancy < 3 months.

2. Subject with primacy central nervous system (CNS) malignancy or symptomatic CNS (leptomeningeal or brain) metastases.

3. Pregnant or nursing females.

4. Subjects who have had major surgery within 28 days prior to screening.

5. Serious underlying medical conditions, including but not limited to un-controlled hypertension, other cardiovascular disease or diabetes, ongoing or active infection, psychiatric, psychological, familial or geographical condition that, in the judgment of the investigator, may interfere the compliance with study treatment.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Neoplasm Metastasis
• Neoplasms
• Non-Small-Cell Lung Cancer

Intervention

Drug:
• EMB-01
In part 1, patients will receive intravenous infusions of EMB01 weekly (QW). Dose escalation will continue until the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) is reached or all planned doses are administered. In part 2, participants will receive intravenous infusion of EMB-01 at RP2D The duration of each treatment cycle in both part 1 and part 2 is 28 days (4 weeks). Participants may continue to receive study drug until discontinuation criteria are met.

Locations

Country	Name	City	State
China	Guangdong General Hospital	Guangzhou	Guang Dong
China	Shanghai Chest Hosptial	Shanghai	Shanghai
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Gabrail Cancer Center Research	Canton	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai EpimAb Biotherapeutics Co., Ltd.	Covance

Countries where clinical trial is conducted

United States,  China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pharmacodynamic (Soluble EGFR and cMET concentration)	Pharmacodynamic (Soluble EGFR and cMET concentration)	Through treatment discontinuation: an average of 6 months
Primary	Maximum tolerated dose (MTD) (phase 1 only)	Maximum tolerated dose	cycle 1 (1cycle = 28 days)
Primary	Adverse Events (AEs), and Serious Adverse Events (SAEs)	Adverse Events, and Serious Adverse Events	Screening up to follow-up (30 days after the last dose)
Primary	Overall Response Rate (ORR) (phase 2 only)	Overall Response Rate	From the date fo dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Secondary	Maximum Serum Concentration (Cmax)	Maximum Serum Concentration	Through treatment discontinuation: an average of 6 months
Secondary	Area Under the Plasma Concentration-Time Curve (AUC)	Area Under the Plasma Concentration-Time Curve	Through treatment discontinuation: an average of 6 months
Secondary	Trough Serum Concentration (Ctrough)	Trough Serum Concentration	Through treatment discontinuation: an average of 6 months
Secondary	Elimination half-life (t1/2)	Elimination half-life	Through treatment discontinuation: an average of 6 months
Secondary	Clearance (CL)	Clearance	Through treatment discontinuation: an average of 6 months
Secondary	Volume of distribution at steady state (Vss)	volume of distribution at steady state	Through treatment discontinuation: an average of 6 months
Secondary	Accumulation Ratio (AR)	Accumulation Ratio	hrough treatment discontinuation: an average of 6 months
Secondary	Dose Proportionality	Dose Proportionality	Through treatment discontinuation: an average of 6 months
Secondary	Anti-Drug Antibodies (ADA)	Anti-Drug Antibodies	Through study completion, an average of 7 months
Secondary	Duration Of Response (DOR)	Duration Of Response	From the date fo dosing until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months
Secondary	Progression-Free Survival (PFS)	Progression-free survival	Through treatment discontinuation: an average of 6 months