Description:
First-in-human, Phase I/II, Multicenter, Open-Label Study of EMB-01 in Patients with
Advanced/Metastatic Solid Tumors
Title
- Brief Title: A Dose Escalation Study of EMB-01 in Participants With Advanced/Metastatic Solid Tumors
- Official Title: First-in-human, Phase I/II, Multicenter, Open-Label Study of EMB-01 in Patients With Advanced/Metastatic Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
EMB01X101
- NCT ID:
NCT03797391
Conditions
- Neoplasms
- Neoplasm Metastasis
- Non-Small-Cell Lung Cancer
Interventions
Drug | Synonyms | Arms |
---|
EMB-01 | FIT-013a | Dose Escalation-Part 1, Expansion-Part 2 |
Purpose
First-in-human, Phase I/II, Multicenter, Open-Label Study of EMB-01 in Patients with
Advanced/Metastatic Solid Tumors
Detailed 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).
Trial Arms
Name | Type | Description | Interventions |
---|
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). Participants may continue to receive study drug until discontinuation criteria are met. 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). | |
Eligibility Criteria
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. 4) Must have adequate organ function
4. Regarding prior anti-tumor therapy:
a. 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.
c. Patients must have recovered to ≤Grade 1 from the adverse effects of such above
treatment before beginning study treatment.
5. 6) 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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Maximum tolerated dose (MTD) (phase 1 only) |
Time Frame: | cycle 1 (1cycle = 28 days) |
Safety Issue: | |
Description: | Maximum tolerated dose |
Secondary Outcome Measures
Measure: | Maximum Serum Concentration (Cmax) |
Time Frame: | Through treatment discontinuation: an average of 6 months |
Safety Issue: | |
Description: | Maximum Serum Concentration |
Measure: | Area Under the Plasma Concentration-Time Curve (AUC) |
Time Frame: | Through treatment discontinuation: an average of 6 months |
Safety Issue: | |
Description: | Area Under the Plasma Concentration-Time Curve |
Measure: | Trough Serum Concentration (Ctrough) |
Time Frame: | Through treatment discontinuation: an average of 6 months |
Safety Issue: | |
Description: | Trough Serum Concentration |
Measure: | Elimination half-life (t1/2) |
Time Frame: | Through treatment discontinuation: an average of 6 months |
Safety Issue: | |
Description: | Elimination half-life |
Measure: | Clearance (CL) |
Time Frame: | Through treatment discontinuation: an average of 6 months |
Safety Issue: | |
Description: | Clearance |
Measure: | Volume of distribution at steady state (Vss) |
Time Frame: | Through treatment discontinuation: an average of 6 months |
Safety Issue: | |
Description: | volume of distribution at steady state |
Measure: | 7. Accumulation Ratio (AR) |
Time Frame: | hrough treatment discontinuation: an average of 6 months |
Safety Issue: | |
Description: | Accumulation Ratio |
Measure: | Dose Proportionality |
Time Frame: | Through treatment discontinuation: an average of 6 months |
Safety Issue: | |
Description: | Dose Proportionality |
Measure: | Anti-Drug Antibodies (ADA) |
Time Frame: | Through study completion, an average of 7 months |
Safety Issue: | |
Description: | Anti-Drug Antibodies |
Measure: | Duration Of Response (DOR) (phase 2 only) |
Time Frame: | 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 |
Safety Issue: | |
Description: | Duration Of Response |
Measure: | Progression-Free Survival (PFS) (phase 2 only) |
Time Frame: | Through treatment discontinuation: an average of 6 months |
Safety Issue: | |
Description: | Progression-free survival |
Measure: | Clinical Benefit Rate (CBR) (phase 2 only) |
Time Frame: | Through treatment discontinuation: an average of 6 months |
Safety Issue: | |
Description: | Clinical Benefit Rate |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Shanghai EpimAb Biotherapeutics Co., Ltd. |
Trial 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
Last Updated
July 23, 2021