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

• ClinicalTrials.gov Identifier: NCT03797391
• Recruitment Status: Recruiting
• First Posted: January 9, 2019
• Last Update Posted: May 31, 2023
• Sponsor: Shanghai EpimAb Biotherapeutics Co., Ltd.
• Collaborator: Covance
• Information provided by (Responsible Party): Shanghai EpimAb Biotherapeutics Co., Ltd.

Tracking Information

• First Submitted Date: December 26, 2018
• First Posted Date: January 9, 2019
• Last Update Posted Date: May 31, 2023
• Actual Study Start Date: December 13, 2018
• Estimated Primary Completion Date: March 14, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 16, 2021)

• Maximum tolerated dose (MTD) (phase 1 only) [ Time Frame: cycle 1 (1cycle = 28 days) ]
  Maximum tolerated dose
• Adverse Events (AEs), and Serious Adverse Events (SAEs) [ Time Frame: Screening up to follow-up (30 days after the last dose) ]
  Adverse Events, and Serious Adverse Events
• Overall Response Rate (ORR) (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 ]
  Overall Response Rate

Original Primary Outcome Measures (submitted: January 6, 2019)

• Maximum tolerated dose (MTD) [ Time Frame: cycle 1 (1cycle = 28 days) ]
  Maximum tolerated dose
• Adverse Events (AEs), and Serious Adverse Events (SAEs) [ Time Frame: Screening up to follow-up (30 days after the last dose) ]
  Adverse Events, and Serious Adverse Events
• Overall Response Rate (ORR) [ 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 ]
  Overall Response Rate
• Duration Of Response (DOR) [ 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 ]
  Duration Of Response
• Progression-Free Survival (PFS) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Progression-free survival

Current Secondary Outcome Measures (submitted: August 30, 2021)

• Maximum Serum Concentration (Cmax) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Maximum Serum Concentration
• Area Under the Plasma Concentration-Time Curve (AUC) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Area Under the Plasma Concentration-Time Curve
• Trough Serum Concentration (Ctrough) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Trough Serum Concentration
• Elimination half-life (t1/2) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Elimination half-life
• Clearance (CL) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Clearance
• Volume of distribution at steady state (Vss) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  volume of distribution at steady state
• Accumulation Ratio (AR) [ Time Frame: hrough treatment discontinuation: an average of 6 months ]
  Accumulation Ratio
• Dose Proportionality [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Dose Proportionality
• Anti-Drug Antibodies (ADA) [ Time Frame: Through study completion, an average of 7 months ]
  Anti-Drug Antibodies
• Duration Of Response (DOR) [ 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 ]
  Duration Of Response
• Progression-Free Survival (PFS) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Progression-free survival

Original Secondary Outcome Measures (submitted: January 6, 2019)

• Maximum Serum Concentration (Cmax) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Maximum Serum Concentration
• Area Under the Plasma Concentration-Time Curve (AUC) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Area Under the Plasma Concentration-Time Curve
• Trough Serum Concentration (Ctrough) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Trough Serum Concentration
• Elimination half-life (t1/2) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Elimination half-life
• Clearance (CL) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  Clearance
• Volume of distribution at steady state (Vss) [ Time Frame: Through treatment discontinuation: an average of 6 months ]
  volume of distribution at steady state
• Anti-Drug Antibodies (ADA) [ Time Frame: Through study completion, an average of 7 months ]
  Anti-Drug Antibodies
• Pharmacodynamics (PD) [ Time Frame: Up to 8 weeks ]
  Exploratory biomarker analysis of EGFR and cMet levels in tumor samples

Current Other Pre-specified Outcome Measures (submitted: July 16, 2021)

Pharmacodynamic (Soluble EGFR and cMET concentration) [ Time Frame: Through treatment discontinuation: an average of 6 months ]

Pharmacodynamic (Soluble EGFR and cMET concentration)

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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).
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:

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

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

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

Intervention

Drug: EMB-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.

Other Name: FIT-013a

Study Arms

Experimental: Dose Escalation-Part 1, Expansion-Part 2

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).

Intervention: Drug: EMB-01

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 30, 2021): 186
• Original Estimated Enrollment (submitted: January 6, 2019): 33
• Estimated Study Completion Date: January 15, 2026
• Estimated Primary Completion Date: March 14, 2025 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Xiaodong Sun, MD; +86-21-61043299; xdsun@epimab.com

Contact: Xuemei Xie; +86-21-61043299; xmxie@epimab.com

• Listed Location Countries: China, United States

Administrative Information

• NCT Number: NCT03797391
• Other Study ID Numbers: EMB01X101
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Shanghai EpimAb Biotherapeutics Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Shanghai EpimAb Biotherapeutics Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Covance
• Investigators: Not Provided
• PRS Account: Shanghai EpimAb Biotherapeutics Co., Ltd.
• Verification Date: May 2023