Neoplasm Metastasis, Neoplasms, Non-Small-Cell Lung Cancer
Conditions
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
Brief summary
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).
Interventions
DRUGEMB-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.
Sponsors
Covance
Shanghai EpimAb Biotherapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation followed by Protocol at 100mg, 200mg, 350mg, 500mg, 700mg, 900mg, 1200mg, 1600mg, 2100mg, 2700mg and 3000mg .
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) (phase 2 only) | 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 | Overall Response Rate |
| Maximum tolerated dose (MTD) (phase 1 only) | cycle 1 (1cycle = 28 days) | Maximum tolerated dose |
| Adverse Events (AEs), and Serious Adverse Events (SAEs) | Screening up to follow-up (30 days after the last dose) | Adverse Events, and Serious Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Accumulation Ratio (AR) | hrough treatment discontinuation: an average of 6 months | Accumulation Ratio |
| Maximum Serum Concentration (Cmax) | Through treatment discontinuation: an average of 6 months | Maximum Serum Concentration |
| Area Under the Plasma Concentration-Time Curve (AUC) | Through treatment discontinuation: an average of 6 months | Area Under the Plasma Concentration-Time Curve |
| Trough Serum Concentration (Ctrough) | Through treatment discontinuation: an average of 6 months | Trough Serum Concentration |
| Clearance (CL) | Through treatment discontinuation: an average of 6 months | Clearance |
| Volume of distribution at steady state (Vss) | Through treatment discontinuation: an average of 6 months | volume of distribution at steady state |
| Duration Of Response (DOR) | 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 | Duration Of Response |
| Progression-Free Survival (PFS) | Through treatment discontinuation: an average of 6 months | Progression-free survival |
| Elimination half-life (t1/2) | Through treatment discontinuation: an average of 6 months | Elimination half-life |
| Dose Proportionality | Through treatment discontinuation: an average of 6 months | Dose Proportionality |
| Anti-Drug Antibodies (ADA) | Through study completion, an average of 7 months | Anti-Drug Antibodies |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic (Soluble EGFR and cMET concentration) | Through treatment discontinuation: an average of 6 months | Pharmacodynamic (Soluble EGFR and cMET concentration) |
Countries
China, United States
Contacts
Primary ContactXiaodong Sun, MD
Backup ContactXuemei Xie
Outcome results
None listed