First-In-Human Study of Bispecific Antibody MR001 In Subjects With Advanced Solid Tumors

Clinical Study on Evaluating the Safety and Tolerability of Bispecific Antibody MR001 in Patients With Advanced Solid Tumors.

Phase 1 open-label study to evaluate the safety, tolerability and preliminary efficacy of bispecific antibody MR001 and to determine the maximal tolerated dose and designate the recommended phase 2 dose in subjects with locally advanced or metastatic solid cancers.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: MR001

Detailed Description

Phase 1 open-label study to evaluate the safety, tolerability and preliminary efficacy of bispecific antibody MR001 and to determine the maximal tolerated dose and designate the recommended phase 2 dose in subjects with locally advanced or metastatic solid cancers. The study will be conducted in 2 parts: part 1 will involve dose escalation and part 2 will involve expansion of the recommended phase 2 dose.

• Study Type: Interventional
• Enrollment (Estimated): 31
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Guoxin Li, MD; Phone Number: +86 13802771450; Email: gzliguoxin@163.com
• Study Contact Backup: Name: Shun Li, PhD; Phone Number: +86 14776580498; Email: lis@majory.com.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510-515
      • Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age ≥18 years old and ≤75 years old (including the critical value);
2. Patients with histologically or cytologically confirmed advanced metastatic solid tumors who have failed standard treatments, are intolerant to standard treatments, or refuse standard treatments;
3. According to RECIST 1.1 criteria, there is at least 1 evaluable target lesion;
4. ECOG score physical status is 0-2;

5. Have appropriate organs and hematopoietic function, and no serious organ dysfunction according to the following laboratory tests:

   Hematology: absolute neutrophil count (ANC) ≥1.5×10e9/L, platelets ≥100×10e9/L, white blood cell count ≥3×10e9/L, hemoglobin ≥90 g/L; Renal function: serum creatinine ≤1.5 times the upper limit of normal (ULN) or creatinine clearance ≥50 mL/min (creatinine clearance using the Cockcroft-Gault formula); Liver function: AST and ALT ≤ 2.5 times ULN, patients with liver metastasis ≤ 5 times ULN; serum bilirubin (TBIL) ≤ 1.5 times ULN; alkaline phosphatase ≤ 1.5 times ULN, patients with liver metastasis or bone metastasis ≤ 5 times ULN ; Coagulation function: international normalized rate (INR) or activated partial thromboplastin time (APTT) ≤ 1.5 times ULN;

6. CD4+T lymphocyte count >350 cells/μL;
7. Expected survival ≥3 months;
8. No birth plans within 2 weeks before screening and 3 months after the end of the trial and agree to take effective non-drug contraceptive measures during the trial;
9. Voluntarily participate in the trial and sign the informed consent form.

Exclusion Criteria:

1. Those who are allergic to trial drugs or excipients;
2. Subjects with uncontrolled active brain metastasis or meningeal metastasis: those who need to use any radiation, surgery or drug treatment (including steroids, anticonvulsant drugs, etc.) to control metastasis symptoms 1 month before screening are not allowed Enrollment, patients with stable brain metastases can be enrolled;
3. Those who have suffered from autoimmune diseases in the past and need to use glucocorticoids or immunosuppressive drugs;
4. Uncontrolled comorbidities or cancer pain;
5. Hypertension that remains uncontrollable after drug treatment (systolic blood pressure >170 mmHg or diastolic blood pressure >100 mmHg);
6. Those with a history of severe heart disease, such as: a history of acute myocardial infarction or coronary angioplasty or stent implantation within 12 months, unstable angina, myocarditis, chronic heart failure ≥ grade III (New York, USA) Heart Association standards), or those with a history of QT interval prolongation (>470 ms for women; >450 ms for men) or a history of severe arrhythmia as shown by electrocardiogram;
7. Those with a history of severe kidney disease, such as chronic nephritis, renal insufficiency, etc.;
8. There is currently an uncontrolled active infection;
9. Active hepatitis B (HBsAg positive, and peripheral blood HBV DNA titer test ≥1×10e3 IU/mL), hepatitis C, syphilis-specific antibodies and human immunodeficiency virus (HIV) antibody screening Patients with positive test results;
10. Other malignant tumors occurred within 5 years before screening, except for cervical cancer in situ, cutaneous squamous cell carcinoma or basal cell carcinoma that has been previously treated for radical treatment;
11. Those who have received the COVID-19 vaccine within 28 days before screening or have received other vaccines within 3 months before screening or plan to receive vaccines during the trial;
12. Subjects who received systemic steroid treatment within 14 days before the first dose and were judged by the investigator to need long-term systemic steroid treatment during treatment (except for inhaled or topical use, physiological replacement dose);
13. Participated in any other interventional clinical trial within 28 days before the first dose;
14. Received blood transfusion and/or colony-stimulating factor-related treatment within 28 days before the first dose;
15. Those who have received major surgical and/or anti-tumor treatments (including but not limited to chemotherapy, radiotherapy, targeted and immunotherapy, etc.) within 28 days before the first dose, and have failed to recover from the toxicity of these interventions (according to NCI-CTCAE version 5.0 toxicity has not returned to ≤ grade 1), except for alopecia;
16. Women preparing for pregnancy, pregnancy, and lactation;
17. Any other circumstances that the researcher believes may increase the risk to the subjects or interfere with the results of the trial, and who are deemed unsuitable to enter this trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MR001; The investigational product is MR001 which will be supplied in glass vials containing 50 mg of Freeze-dried powder. MR001 could be diluted in saline for intravenous (IV) administration.

Drug: MR001; Dose Level 1: 0.5 mg/kg Intravenously (IV) Frequency: administered on Day 1 of each cycle (every 3 weeks), 1 cycle Dose Level 2: 2 mg/kg Intravenously (IV) Frequency: administered on Day 1 of each cycle (every 3 weeks), 4 cycle Dose Level 3: 6 mg/kg Intravenously (IV) Frequency: administered on Day 1 of each cycle (every 3 weeks), 4 cycle Dose Level 4: 10 mg/kg Intravenously (IV) Frequency: administered on Day 1 of each cycle (every 3 weeks), 4 cycle Dose Level 5: 15 mg/kg Intravenously (IV) Frequency: administered on Day 1 of each cycle (every 3 weeks), 4 cycle Dose Level 6: 20 mg/kg Intravenously (IV) Frequency: administered on Day 1 of each cycle (every 3 weeks), 4 cycle; Other Names: anti-CD4/anti-TGFβ1 bispecific antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events, and serious adverse events	Safety profile of MR001	12 months
Dose Limited Toxicity (DLT) and Maximum Tolerated Dose (MTD)	Determine the DLT and MTD and designate a recommended phase 2 dose (RP2D)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Time (Tmax) of MR001	Determine the Tmax of MR001	12 months
Maximum Plasma Concentration (Cmax) of MR001	Determine the Cmax of MR001	12 months
Area under the Concentration versus Time Curve (AUC) of MR001	Determine the AUC(0-t) and AUC(0-∞) of MR001	12 months
Elimination of Half-life (t1/2) of MR001	Determine the t1/2 of MR001	12 months
Clearance (CL) of MR001	Determine the CL of MR001	12 months
Volume of Distribution (Vd) of MR001	Determine the Vd of MR001	12 months
Objective Response Rate (ORR)	ORR in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and modified RECIST guidelines for immunotherapy trials (iRECIST).	12 months
Progression Free Survival (PFS)	Progression-free Survival (PFS) by RECIST Version 1.1 and iRECIST.	12 months
Overall Survival (OS)	Overall Survival (OS) by RECIST Version 1.1 and iRECIST.	12 months
Duration of Response (DOR)	Duration of Response (DOR) by RECIST Version 1.1 and iRECIST.	12 months
Disease Control Rate (DCR)	Disease Control Rate (DCR) by RECIST Version 1.1 and iRECIST.	12 months
Anti-drug Antibody (ADA)	Determine the Anti-MR001 antibody in the plasma	12 months

Collaborators and Investigators

• Sponsor: Nanfang Hospital, Southern Medical University
• Investigators: Principal Investigator: Guoxin Li, MD, Nanfang Hospital, Southern Medical University

Publications and helpful links

General Publications

• Li S, Liu M, Do MH, Chou C, Stamatiades EG, Nixon BG, Shi W, Zhang X, Li P, Gao S, Capistrano KJ, Xu H, Cheung NV, Li MO. Cancer immunotherapy via targeted TGF-beta signalling blockade in TH cells. Nature. 2020 Nov;587(7832):121-125. doi: 10.1038/s41586-020-2850-3. Epub 2020 Oct 21.
• Liu M, Kuo F, Capistrano KJ, Kang D, Nixon BG, Shi W, Chou C, Do MH, Stamatiades EG, Gao S, Li S, Chen Y, Hsieh JJ, Hakimi AA, Taniuchi I, Chan TA, Li MO. TGF-beta suppresses type 2 immunity to cancer. Nature. 2020 Nov;587(7832):115-120. doi: 10.1038/s41586-020-2836-1. Epub 2020 Oct 21.

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: October 16, 2023
• First Submitted That Met QC Criteria: November 12, 2023
• First Posted (Estimated): November 16, 2023

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 12, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Bispecific
• Other Study ID Numbers: NFEC-2023-382

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No