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

NCT03797391 | Unknown Phase 1 FDA Drug

• 1 other identifier: EMB01X101
• Study Type: interventional
• Target: 186
• Locations: 2 countries
• Sites: 5

Brief Summary

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

Conditions

Neoplasms; Neoplasm Metastasis; Non-Small-Cell Lung Cancer

Keywords

Human Bispecific antibody,; Epidermal Growth Factor Receptor (EGFR),; c-Mesenchymal-Epithelial Transition (cMet),; Neoplasms, Neoplasm Metastasis,; Non-Small-Cell Lung Cancer (NSCLC), First-in-human,; EMB-01, Tyrosine Kinase Inhibitor (TKI) Resistant

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) (phase 1 only)

  Maximum tolerated dose

  cycle 1 (1cycle = 28 days)

• 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)

• 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 Outcomes (11)

• Maximum Serum Concentration (Cmax)

  Through treatment discontinuation: an average of 6 months

• Area Under the Plasma Concentration-Time Curve (AUC)

  Through treatment discontinuation: an average of 6 months

• Trough Serum Concentration (Ctrough)

  Through treatment discontinuation: an average of 6 months

• Elimination half-life (t1/2)

  Through treatment discontinuation: an average of 6 months

• Clearance (CL)

  Through treatment discontinuation: an average of 6 months

Other Outcomes (1)

• Pharmacodynamic (Soluble EGFR and cMET concentration)

  Through treatment discontinuation: an average of 6 months

Study Arms (1)

Dose Escalation-Part 1, Expansion-Part 2

EXPERIMENTAL

In part 1, escalating dose cohort, patients will receive intravenous infusions of EMB-01 weekly (QW). The duration of each treatment cycle is 28 days (4 weeks). 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 the recommended Phase II dose (RP2D) regimen(s) once weekly. The duration of each treatment cycle is 28 days (4 weeks).

Drug: EMB-01

Interventions

EMB-01 DRUG

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.

Also known as: FIT-013a

Dose Escalation-Part 1, Expansion-Part 2

Eligibility Criteria

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

You may qualify if:

• 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.
• Able to understand and willing to sign the Informed Consent Form (ICF).
• 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.
• Must have adequate organ function.
• Regarding prior anti-tumor therapy:
• Must have stopped treatment at least 4 weeks or within 5 half-lives.
• 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.
• Patients must have recovered to ≤Grade 1 from the adverse effects of such above treatment before beginning study treatment.
• 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.
• ECOG score 0 or 1 for phase I, and ≤2 for phase II.

You may not qualify if:

• Subject who meets any of the follow criteria can't be proceeded to clinical screening:
• Patients who are unwilling to sign the molecular pre-screening ICF.
• Life expectancy \< 3 months.
• Subject with primacy central nervous system (CNS) malignancy or symptomatic CNS (leptomeningeal or brain) metastases.
• Pregnant or nursing females.
• Subjects who have had major surgery within 28 days prior to screening.
• 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.

Sponsors & Collaborators

• Shanghai EpimAb Biotherapeutics Co., Ltd.: lead
• Covance: collaborator

Study Sites (5)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

RECRUITING

Guangdong General Hospital

Guangzhou, Guangdong, 510080, China

RECRUITING

Shanghai Chest Hosptial

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Xiaodong Sun, MD

CONTACT

+86-21-61043299; xdsun@epimab.com

Xuemei Xie

CONTACT

+86-21-61043299; xmxie@epimab.com

Study Design

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

Model Details: Dose escalation followed by Protocol at 100mg, 200mg, 350mg, 500mg, 700mg, 900mg, 1200mg, 1600mg, 2100mg, 2700mg and 3000mg .

Study Record Dates

• First Submitted: December 26, 2018
• First Posted: January 9, 2019
• Study Start: December 13, 2018
• Primary Completion: March 14, 2025
• Study Completion: January 15, 2026
• Last Updated: May 31, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); CN (2)