A Phase I/II Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of the EMB-07 Combination Therapy in Patients With Aggressive B-Cell Non-Hodgkin Lymphoma

A Phase I/II, Open-label, Multicenter Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of EMB-07 (a Bispecific Antibody Targeting CD3 and Receptor-tyrosine-kinase-like Orphan Receptor 1 [ROR1]) Combination Therapy in Patients With Aggressive B-cell Non-Hodgkin Lymphoma

This is an open-label, multicenter, Phase I/II study designed to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary efficacy of EMB-07 combination therapy in adult patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). The study consists two phases: Phase I of dose escalation and Phase II of dose expansion. Approximately 115 patients will be enrolled in this study (i.e., 5 cohorts of approximately 23 patients per cohort). Multiple EMB-07-based combination regimens will be evaluated in patients with relapsed/refractory (R/R) aggressive B-NHL (Cohort A) and patients with newly diagnosed aggressive B-NHL (Cohort B).

Study Overview

• Status: Not yet recruiting
• Conditions: Aggressive B-Cell Non-Hodgkin Lymphoma; Combination Therapy; EMB07; phaseI/II
• Intervention / Treatment: Drug: EMB07; Drug: Rituximab/Gemcitabine/Oxaliplatin

• Study Type: Interventional
• Enrollment (Estimated): 115
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xikang Xu; Phone Number: 86-21-61951000; Email: xkxu@epimab.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability to understand and voluntarily sign the Informed Consent Form (ICF);
2. Patients aged ≥18 years;
3. Life expectancy > 12 weeks;
4. ECOG performance status score: ≤1 point during the dose escalation phase, ≤2 points during the dose expansion phase.
5. Cohort A: Pathologically confirmed aggressive R/R B-NHL, including DLBCL, not otherwise specified (NOS), or DLBCL transformed from indolent lymphoma (e.g., follicular lymphoma) (t-DLBCL), or other aggressive B-NHL judged to potentially benefit from study treatment by the investigator and sponsor (e.g., high-grade B-cell lymphoma [HGBL], Richter transformation, other large B-cell lymphoma subtypes).

Cohort B: Newly diagnosed, treatment-naïve DLBCL NOS confirmed by pathology, or t-DLBCL not previously treated with adequate (at least 2 cycles) R-CHOP therapy (excluding Richter transformation or HGBL with BCL2/MYC±BCL6 rearrangements). Patients with newly diagnosed DLBCL NOS should have an International Prognostic Index (IPI) score ≥2 and Ann Arbor stage ≥2. The sponsor will reserve the right to limit the number of t-DLBCL patients enrolled in the study. Other aggressive B-NHLs patients who may benefit from the study treatment can be enrolled after careful risk/benefit assessment by the sponsor and investigator.

Exclusion Criteria:

1. Current or prior central nervous system (CNS) or meningeal involvement related to the underlying disease.
2. Cohort A: Prior exposure to any ROR1-targeted agent (e.g., biologic or CAR-T); or Cohort A1: Prior exposure to Gemcitabine-based chemotherapy (≥ 2 consecutive cycles); or Cohort A2: Prior exposure to Polatuzumab Vedotin; or Cohorts A3 and A4: Refractory to prior Lenalidomide/Zanubrutinib or Chidamide therapy, respectively.
3. Contraindications to any agent included in the combination therapy regimen.
4. Cohort A: Candidates suitable for ASCT or CAR-T cell therapy.
5. Cohort A: Use of any standard or investigational therapy for the underlying disease within 28 days before C1D1 or 5 half-lives (whichever is shorter), including chemotherapy, immunotherapy, radioimmunotherapy, non-palliative radiotherapy, or any other anti-tumor therapy. Only palliative radiotherapy to non-target lesions will be permitted.
6. Cohort B: B-NHL with prior receipt of at least 2 consecutive cycles of R-CHOP (prior lymph node biopsy or local radiotherapy will not be an exclusion criterion).
7. Major surgery or live vaccine administration within 28 days prior to C1D1.
8. History of allogeneic hematopoietic stem cell transplantation or solid organ transplantation (except corneal transplantation). In addition, patients who received ASCT within 3 months before C1D1, CAR-T within 6 months before C1D1, or diagnosed with graft-versus-host disease (GVHD) will be excluded.
9. Any AE related to prior therapy (excluding alopecia) that has not resolved to Grade ≤ 1 (per the Common Terminology Criteria for Adverse Events [CTCAE], Version 5.0) or baseline at C1D1.
10. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening. Patients with positive HBsAg and/or positive HBcAb but negative HBV DNA will be eligible for enrollment. Patients with positive HCV antibody but negative HCV RNA are also eligible for enrollment.
11. Known positive HIV serology or history of active viral infection
12. Active infection requiring parenteral antibiotics, antivirals, or antifungals within 14 days before C1D1; prophylactic use of these agents (including parenteral administration) will be permitted.
13. Prior malignancy requiring treatment or with evidence of recurrence within 5 years before C1D1 (except non-melanoma skin cancer or adequately treated carcinoma in situ of the cervix). Patients with a history of cancer treated with curative intent > 5 years before C1D1 and no evidence of recurrence will be eligible.
14. Ischemic or hemorrhagic stroke of Grade ≥ 3, or gastrointestinal bleeding of Grade ≥ 3, within 6 months before C1D1.

15. Active, unstable cardiovascular function:

    • Myocardial infarction within 6 months before C1D1;
    • Unstable angina within 3 months before C1D1;
    • Clinically significant uncontrolled arrhythmias (e.g., sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes);
    • Mobitz type II second-degree or third-degree atrioventricular block;
    • Congestive heart failure at class ≥ 3 per New York Heart Association (NYHA)
    • Known left ventricular ejection fraction (LVEF) < 50%.
16. Known or suspected history of hemophagocytic lymphohistiocytosis (HLH);
17. Known history of progressive multifocal leukoencephalopathy;

18. Active autoimmune disease requiring treatment

    • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid hormone replacement will be eligible.
    • Type 1 diabetes mellitus well-controlled with insulin therapy will be permitted.
    • Patients with a history of autoimmune hepatitis, systemic lupus erythematosus, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, granulomatosis with polyangiitis, Sjögren's syndrome, multiple sclerosis, or glomerulonephritis will be excluded.
    • Patients with a history of immune thrombocytopenic purpura, autoimmune hemolytic anemia, Guillain-Barré syndrome, myasthenia gravis, myositis, rheumatoid arthritis, vasculitis, or other autoimmune diseases are excluded unless no systemic therapy has been required in the past 12 months.
19. Prior systemic immunosuppressive medication (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 28 days before C1D1.
20. Systemic corticosteroid use within 2 weeks before study treatment at a dose equivalent to > 10 mg/day Prednisone. Inhaled, topical, or ophthalmic steroids will be permitted. Short-term corticosteroid use (e.g., prophylaxis for intravenous contrast) will be permitted.
21. Any other severe underlying medical condition (e.g., active gastric ulcer, uncontrolled seizures, cerebrovascular event, gastrointestinal bleeding, coagulation/thrombotic disorders with severe signs/symptoms, cardiac disease), or psychiatric, psychological, familial, or geographic factors that, in the investigator's judgment, possibly interfere with scheduled disease assessments, treatment, and follow-up, compromise patient compliance, or place the patient at high risk of treatment-related complications.
22. Female patients who are pregnant or breastfeeding. Abuse of alcohol, cannabis-derived products, or other controlled substances.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Phase I: Dose Escalation, Phase II: Dose Expansion; Phase I: Dose Escalation During the dose escalation, the planned starting dose of EMB-07 is 6 mg. A dose escalation scheme of "3+3" will be followed to determine DLT, MTD, and RP2CD. Phase II: Dose Expansion For each cohort: During the dose-expansion, approximately 10 to 15 patients will be enrolled and administrated in each cohort to further characterize the safety profile and anti-tumor activity of the combination therapies. Approximately 20 patients per cohort receiving RP2CD will be pooled from the dose escalation and dose expansion phases to evaluate preliminary efficacy signals.

Drug: EMB07; EMB-07 is a bispecific antibody targeting CD3 and receptor-tyrosine-kinase-like orphan receptor 1 [ROR1]; Drug: Rituximab/Gemcitabine/Oxaliplatin; Rituximab is a monoclonal antibody drug specifically targeting the CD20 antigen. Gemcitabine is a chemotherapy drug classified as an antimetabolite. Oxaliplatin is a platinum-based chemotherapy drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Adverse Events (AE) and Serious Adverse Events (SAE)	Adverse events and serious adverse events as assessed by CTCAE v5.0	From enrollment up to 30 days after the last dose
Maximum tolerated dose (MTD) of EMB-07（Phase I only）		Up to 28 days
Recommended phase II dose (RP2D) of EMB-07		Up to 28 days
Objective Response Rate (ORR)	Objective response rate, measured by Lugano 2014	From first dose until the date of first documented progression or date of death from any cause, whichever comes first, up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	Time from first study drug dose to first documented disease progression (per Lugano 2014 criteria) or death from any cause, whichever occurs first.	From first dose until the date of first documented progression or date of death from any cause, whichever comes first; up to 2 years
Duration of Complete Response（DOCR）	Time from first study drug dose to first documented disease progression (per Lugano 2014 criteria) or death from any cause, whichever occurs first.	From first dose until the date of first documented progression or date of death from any cause, whichever comes first; up to 2 years
Time to Treatment Response（TTR）	Time from first study drug dose to first documented disease progression (per Lugano 2014 criteria) or death from any cause, whichever occurs first.	From first dose until the date of first documented progression or date of death from any cause, whichever comes first; up to 2 years
Time to Complete Response（TTCR）	Time from first study drug dose to first documented disease progression (per Lugano 2014 criteria) or death from any cause, whichever occurs first.	From first dose until the date of first documented progression or date of death from any cause, whichever comes first; up to 2 years
Event-Free Survival（EFS）	Time from first study drug dose to first documented disease progression (per Lugano 2014 criteria) or death from any cause, whichever occurs first.	From first dose until the date of first documented progression or date of death from any cause, whichever comes first; up to 2 years
Progression Free Survival (PFS)	Time from first study drug dose to first documented disease progression (per Lugano 2014 criteria) or death from any cause, whichever occurs first.	From first dose until the date of first documented progression or date of death from any cause, whichever comes first; up to 2 years
Overall Survival（OS）	Time from first study drug dose to first documented disease progression (per Lugano 2014 criteria) or death from any cause, whichever occurs first.	From first dose until the date of first documented progression or date of death from any cause, whichever comes first; up to 2 years
Maximum Plasma Concentration (Cmax) of EMB-07	Maximum observed plasma concentration of EMB-07, quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay using human plasma samples.	From predose up to 3 months after first dose
Time to Maximum Plasma Concentration (Tmax) of EMB-07	Time from study drug administration to the time of maximum measured plasma concentration of EMB-07, quantified by validated LC-MS/MS assay using human plasma samples.	From predose up to 30 days after the last dose
Trough Serum Concentration (Ctrough) of EMB-07	Minimum observed serum concentration of EMB-07, measured immediately prior to the next scheduled dose (trough), quantified by validated LC-MS/MS assay using human serum samples.	From predose up to 30 days after the last dose
Anti-Drug Antibody (ADA) Positive Rate of EMB-07	Percentage of subjects testing positive for anti-EMB-07 binding antibodies in serum samples, detected by a validated electrochemiluminescence (ECL) immunoassay.	From predose up to 30 days after the last dose

Collaborators and Investigators

• Sponsor: Shanghai EpimAb Biotherapeutics Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: February 6, 2026
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): February 25, 2026

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived; Rituximab; gemcitabine-oxaliplatin regimen
• Other Study ID Numbers: EMB07X102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No