Clinical trial NCT06031584: A Study of BL-M07D1 in Patients With a Variety of Solid Tumors Including Locally Advanced or Metastatic HER2-positive/Low-expressing Urinary and Gastrointestinal Tumors
Official title: A Phase Ib/II Clinical Study to Evaluate the Safety and Efficacy of BL-M07D1 for Injection in Patients With Locally Advanced or Metastatic HER2-positive/Low-expressing Urinary and Gastrointestinal Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Her2-positive/Low-expression Urinary and Digestive Tract Tumors
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-09-11
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase Ib: Explore the safety and tolerability of BL-M07D1 to further define RP2D in a variety of solid tumors, including locally advanced or metastatic urinary and gastrointestinal tumors. Phase II: To explore the efficacy of BL-M07D1 in patients with a variety of solid tumors including locally advanced or metastatic HER2-positive/low-expressing urinary and gastrointestinal tumors.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily signed informed consent, and follow the plan;
2. No gender limit;
3. Age: ≥18 years old;
4. expected survival time ≥3 months;
5. Patients with histologically and/or cytologically confirmed, unresectable, locally advanced or metastatic HER2-positive/low-expressing urinary and gastrointestinal solid tumors that have failed, are unavailable to, or are not currently suitable for standard therapy. Failure of standard therapy was defined as failure of platinum-based therapy for urothelial carcinoma and failure of standard therapy for biliary tract carcinoma).

   HER2 positive: IHC3 +, or IHC2 + positive and FISH; HER2 low expression: IHC2+ and FISH negative, or IHC1+;
6. Agreed to provide primary tumors or metastases 2 years archive of tumor tissue samples or fresh tissue samples (detect HER2 protein expression in tumor pathological tissue, exploring study its correlation with BL - M07D1 effectiveness index); If the participants can't provide the tumor tissue samples, in accord with other cases, all criteria after researchers assess the can into the group;
7. Must have at least one measurable lesion according to RECIST v1.1 definition;
8. ECOG score 0 or 1;
9. Always anti-tumor treatment toxicity has been restored to NCI - CTCAE v5.0 definition of grade 1 or less, hair loss, fatigue, pigmentation, stable after hormone replacement therapy of hypothyroidism, 2 levels of peripheral nerve toxicity after chemotherapy, except other criteria for the provisions);
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. The level of organ function must meet the following requirements and meet the following standards:

    a) Bone marrow function: absolute neutrophil count (ANC) ≥1.5×109/L, platelet count ≥100×109/L, hemoglobin ≥90 g/L; B) the liver function: total bilirubin (TBIL 1.5 ULN) or less, no liver metastasis of AST and ALT are ULN 2.5 or less, with liver metastasis AST and ALT are 5.0 ULN or less; c) Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to Cockcroft and Gault formula).
12. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN;
13. The urine protein + 2 or 1000 mg / 24 h or less or less;
14. Albumin acuity 30 g/L;
15. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum/urine pregnancy must be negative, and must be non-lactating; All enrolled patients (male or female) were advised to use adequate barrier contraception throughout the treatment cycle and for 6 months after the end of treatment.

Exclusion Criteria:

1. Antineoplastic therapy such as chemotherapy, biological therapy, immunotherapy, radical radiotherapy, major surgery, targeted therapy (including small-molecule tyrosine kinase inhibitors) within 4 weeks or 5 half-life times (whichever is shorter) before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral fluorouracil drugs such as S-1, capecitabine, or palliative radiotherapy within 2 weeks before the first dose; Traditional Chinese medicine or Chinese patent medicine with anti-tumor indications within 2 weeks before the first administration;
2. Prior treatment with an ADC drug containing a camptothecin derivative (topoisomerase I inhibitor) as a toxin;
3. A history of severe cardiovascular and cerebrovascular diseases, including but not limited to:

   1. severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, third degree atrioventricular block, complete left bundle branch block, frequent and uncontrollable arrhythmias, such as atrial fibrillation, atrial flutter, ventricular fibrillation, and ventricular flutter (except transient);
   2. prolonged QT interval at rest (QTc \> 450 msec in men or QTc \> 470 msec in women);
   3. acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first dose;
   4. patients with New York Heart Association (NYHA) functional class ≥II heart failure;
4. Active autoimmune disease or inflammatory diseases, such as: systemic lupus erythematosus, systemic treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and hashimoto's thyroiditis, etc., with the exception of type I diabetes, only replacement therapy can control the hypothyroidism, no systemic treatment of skin disease (e.g., vitiligo, psoriasis);
5. Patients with other malignant tumors within 5 years before the first administration, except those who have been cured skin squamous cell carcinoma, basal cell carcinoma, superficial bladder cancer, prostate/cervix/breast cancer in situ and so on are considered to be eligible for enrollment;
6. Unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring medical intervention within 6 months before screening; Infusion-related thrombosis was excluded;
7. Patients with massive pleural, abdominal and pelvic effusion or pericardial effusion, or with obvious symptoms, or poorly controlled pleural, abdominal and pelvic effusion or pericardial effusion (poorly controlled was defined as requiring more than 2 times of puncture and drainage within one month);
8. Hypertension poorly controlled by antihypertensive drugs (systolic BP \&gt; 150 mmHg or diastolic blood pressure \&gt; 100 mmHg);
9. The existing interstitial lung disease, drug-induced interstitial pneumonia, need steroid treatment of radioactive pneumonia, or has a history of these diseases;
10. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis (meningeal metastases);
11. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any ingredient of BL-M07D1;
12. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT);
13. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, or active hepatitis C virus infection (HCV antibody positive and HCV-RNA \> lower detection limit);
14. Active hepatitis B virus infection (HBV-DNA copy number \> 103 IU/ml) needs to be excluded; Patients with positive hepatitis B surface antigen (HBsAg), HBV-DNA copy number \> central detection limit and ≤103 IU/ml should take anti-hepatitis B virus treatment for at least one week before the first dose;
15. Active infections requiring systemic therapy, such as severe pneumonia, bacteremia, sepsis, etc;
16. Had participated in another clinical trial within 4 weeks before the first dose (calculated from the time of the last dose);
17. Pregnant or lactating women;
18. Other circumstances considered by the investigator to be inappropriate for participation in the trial.

Primary outcomes:
measure: Phase Ib: Recommended Phase II Dose (RP2D)
timeFrame: Up to approximately 24 months
measure: Phase II: Objective response rate (ORR)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Phase Ib/II: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Objective response rate (ORR)
timeFrame: Up to approximately 24 months
measure: Phase Ib/II: Disease control rate (DCR)
timeFrame: Up to approximately 24 months
measure: Phase Ib/II: Duration of response (DOR)
timeFrame: Up to approximately 24 months
measure: Phase II: Progression-free survival (PFS)
timeFrame: Up to approximately 24 months
measure: Phase Ib/II: Cmax
timeFrame: Up to approximately 24 months
measure: Phase Ib/II: Tmax
timeFrame: Up to approximately 24 months
measure: Phase Ib: T1/2
timeFrame: Up to approximately 24 months
measure: Phase Ib: AUC0-t
timeFrame: Up to approximately 24 months
measure: Phase Ib: CL
timeFrame: Up to approximately 24 months
measure: Phase Ib/II: Ctrough
timeFrame: Up to approximately 24 months
measure: Phase Ib/II: Anti-drug antibody (ADA)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Aiping Zhou, PHD
role: PRINCIPAL_INVESTIGATOR
References: