Clinical trial NCT03797391: A Dose Escalation With Expansion 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
Lead sponsor: Shanghai EpimAb Biotherapeutics Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Covance
First posted: 2019-01-09
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation followed by Protocol at 100mg, 200mg, 350mg, 500mg, 700mg, 900mg, 1200mg, 1600mg, 2100mg, 2700mg and 3000mg .
Primary purpose: TREATMENT

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).

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. 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.

Primary outcomes:
measure: Maximum tolerated dose (MTD) (phase 1 only)
timeFrame: cycle 1 (1cycle = 28 days)
measure: Adverse Events (AEs), and Serious Adverse Events (SAEs)
timeFrame: Screening up to follow-up (30 days after the last dose)
measure: Overall Response Rate (ORR) (phase 2 only)
timeFrame: 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:
measure: Maximum Serum Concentration (Cmax)
timeFrame: Through treatment discontinuation: an average of 6 months
measure: Area Under the Plasma Concentration-Time Curve (AUC)
timeFrame: Through treatment discontinuation: an average of 6 months
measure: Trough Serum Concentration (Ctrough)
timeFrame: Through treatment discontinuation: an average of 6 months
measure: Elimination half-life (t1/2)
timeFrame: Through treatment discontinuation: an average of 6 months
measure: Clearance (CL)
timeFrame: Through treatment discontinuation: an average of 6 months
measure: Volume of distribution at steady state (Vss)
timeFrame: Through treatment discontinuation: an average of 6 months
measure: Accumulation Ratio (AR)
timeFrame: hrough treatment discontinuation: an average of 6 months
measure: Dose Proportionality
timeFrame: Through treatment discontinuation: an average of 6 months
measure: Anti-Drug Antibodies (ADA)
timeFrame: Through study completion, an average of 7 months
measure: Duration Of Response (DOR)
timeFrame: 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
measure: Progression-Free Survival (PFS)
timeFrame: Through treatment discontinuation: an average of 6 months
Other outcomes:
measure: Pharmacodynamic (Soluble EGFR and cMET concentration)
timeFrame: Through treatment discontinuation: an average of 6 months
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Canton
country: United States
facility: Gabrail Cancer Center Research
state: Ohio
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guang Dong
city: Shanghai
country: China
facility: Shanghai Chest Hosptial
state: Shanghai
Study officials:
References: