Clinical trial NCT06134531: First-In-Human Study of Bispecific Antibody MR001 In Subjects With Advanced Solid Tumors
Official title: Clinical Study on Evaluating the Safety and Tolerability of Bispecific Antibody MR001 in Patients With Advanced Solid Tumors.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
First posted: 2023-11-18
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of treatment-emergent adverse events, and serious adverse events
timeFrame: 12 months
measure: Dose Limited Toxicity (DLT) and Maximum Tolerated Dose (MTD)
timeFrame: 12 months
Secondary outcomes:
measure: Peak Time (Tmax) of MR001
timeFrame: 12 months
measure: Maximum Plasma Concentration (Cmax) of MR001
timeFrame: 12 months
measure: Area under the Concentration versus Time Curve (AUC) of MR001
timeFrame: 12 months
measure: Elimination of Half-life (t1/2) of MR001
timeFrame: 12 months
measure: Clearance (CL) of MR001
timeFrame: 12 months
measure: Volume of Distribution (Vd) of MR001
timeFrame: 12 months
measure: Objective Response Rate (ORR)
timeFrame: 12 months
measure: Progression Free Survival (PFS)
timeFrame: 12 months
measure: Overall Survival (OS)
timeFrame: 12 months
measure: Duration of Response (DOR)
timeFrame: 12 months
measure: Disease Control Rate (DCR)
timeFrame: 12 months
measure: Anti-drug Antibody (ADA)
timeFrame: 12 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Guoxin Li, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.