Clinical trial NCT04618393: A Study of EMB-02 in Participants With Advanced Solid Tumors
Official title: A Phase I/II Trial of EMB-02, a Bi-specific Antibody Against PD-1 and LAG-3, in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors
Keywords: Phase I/II
Bispecific antibody
PD-1
LAG-3
EMB-02
Immuno-oncology
dose escalation
cohort expansion
Neoplasms
Neoplasm Metastasis
advanced solid tumor
Lead sponsor: Shanghai EpimAb Biotherapeutics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-11-05
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Dose escalation followed by Cohort Expansion Phase at the RP2D.
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to identify the recommended Phase 2 dose(s) (RP2Ds) and schedule assessed to be safe for EMB-02 and to characterize the safety and tolerability of EMB-02 at the RP2Ds. Pharmacokinetics (PK), immunogenicity, and the anti-tumor activity of EMB-02 will also be assessed.

Detailed description: This is a Phase I/II, multi-center, open label, multiple-dose, first in human study, designed to assess safety and tolerability, and to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dos(s)e (RP2D\[s\]) for EMB-02 in patients with advanced solid tumors. Pharmacokinetics, pharmacodynamics, immunogenicity, and response will also be assessed.

Eligibility criteria: Inclusion Criteria:

* Willing and able to provide written informed consent.
* Phase I: Patients with histologically or cytologically confirmed locally advanced/metastatic solid tumors and have failed (progressed on, or are intolerant of) standard therapies. Moreover, the disease should be measurable or evaluable per RECIST v1.1
* Phase II Cohort A: Patients with histologically or cytologically confirmed locally advanced/metastatic melanoma, excluding uveal melanoma. \> 1 prior therapy, including prior treatment with PD-1/L1(mandatory) and/or CTLA-4 inhibitors(optional). And the disease is measurable or evaluable per RECIST v1.1
* Archival tumor samples available for retrospective analysis or biopsy will be taken.
* ECOG performance status 0 or 1 for phase I, and ≤2 for phase II; life expectancy \> 3 Months
* Adequate organ function to participate in the trial.
* Recovery from adverse events (AEs) related to prior anticancer therapy.
* Highly effective contraception

Exclusion Criteria:

* Patients who have active autoimmune disease or history of autoimmune disease
* History of severe irAE.
* History of severe allergic reactions
* Use of systemic corticosteroids.
* Symptomatic central nervous system metastases.
* Patients with cardiac dysfunction
* Uncontrolled diabetes mellitus with hemoglobin A1c \> 8% (via medical history)
* Prior treatment with a LAG-3 inhibitor
* Anticancer therapy or radiation \< 5 half-lives or 4 weeks (whichever is shorter) prior to study treatment;
* Prior organ or stem cell/bone marrow transplant.
* Concurrent malignancy \< 5 years prior to entry.
* Patients with active infections.
* Major surgery \< 4 weeks or minor surgery \< 2 weeks prior to study treatment
* Live virus vaccines \< 30 days prior to screening
* Pregnant or breast-feeding females
* Any investigational agents or study drugs from a previous clinical study within 30 days of the first dose of study treatment
* Any other serious underlying medical conditions
* Abuse on alcohol, cannabis- derived products or other drugs

Primary outcomes:
measure: Incidence and severity of adverse events as assessed by CTCAE V5.0
timeFrame: Screening up to follow-up (30 days after the last dose)
measure: Incidence of serious adverse events (SAE)
timeFrame: Screening up to follow-up (30 days after the last dose)
measure: Incidence of dose interruptions
timeFrame: Screening up to follow-up (30 days after the last dose)
measure: Dose intensity
timeFrame: Screening up to follow-up (30 days after the last dose)
measure: The incidence of DLTs during the first cycle of treatment.
timeFrame: First infusion to the end of Cycle 1 (each cycle is 28 days)
measure: Antitumor activity(Objective Response Rate (ORR)
timeFrame: From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months
Secondary outcomes:
measure: Area under the serum concentration-time curve (AUC) of EMB-02
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Maximum serum concentration (Cmax) of EMB-02
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Trough concentration (Ctrough) of EMB-02
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Average concentration over a dosing interval (Css, avg)of EMB-02.
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Terminal half-life (T1/2) of EMB-02
timeFrame: Through treatment until EOT visit, expected average 6 months.
measure: Systemic clearance (CL) of EMB-02
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Steady state volume of distribution (Vss) of EMB-02
timeFrame: Through treatment until EOT visit, expected average 6 months
measure: Progression free survival (PFS) of EMB-02 as assessed by RECIST 1.1
timeFrame: From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months
measure: Duration of response of EMB-02 as assessed by RECIST 1.1
timeFrame: From the date of dosing until the date of first documented progression or date of death from any cause, whichever came first, expected average 6 months
measure: Incidence and titer of anti-drug antibodies stimulated by EMB-02
timeFrame: Up to End of Treatment Follow Up Period (30 days after the last dose)
Other outcomes:
Locations:
city: Colorado Springs
country: United States
facility: University of Colorado Health Medical Group
state: Colorado
city: Greenville
country: United States
facility: Prisma Health-Upstate
state: South Carolina
city: Wollongong
country: Australia
facility: Southern Medical Day Care Centre
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Frankston
country: Australia
facility: Peninsula & South Eastern Haematology & Oncology Group (PASO)
state: Victoria
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Xiamen
country: China
facility: The first Affiliated Hospital of Xiamen University
state: Fujian
city: Handan
country: China
facility: HanDan Central Hospital
state: Hebei
city: Zhengzhou
country: China
facility: HeNan Provincial People's Hospital
state: Henan
city: Suining
country: China
facility: SuiNing Central Hospital
state: Sichuan
Study officials:
References: