Clinical trial NCT06503783: A Study of BL-M17D1 in Patients With Locally Advanced or Metastatic HER2 Positive/Negative Breast Cancer and Other Solid Tumors
Official title: A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of BL-M17D1 in Patients With Locally Advanced or Metastatic HER2 Positive/Negative Breast Cancer and Other Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Solid Tumor
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2024-07-16
Enrollment: 20
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: This study is an open, multicenter, dose-escalation and expansion-enrollment nonrandomized phase I clinical study to evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of BL-M17D1 in patients with locally advanced or metastatic HER2 positive/negative breast cancer and other solid tumors.


Eligibility criteria: Inclusion Criteria:

1. Sign the informed consent form voluntarily and follow the protocol requirements;
2. Gender is not limited;
3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib);
4. Expected survival time ≥3 months;
5. Patients with locally advanced or metastatic HER2-positive/negative breast cancer and other solid tumors;
6. Agree to provide archival tumor tissue samples or fresh tissue samples of primary or metastatic lesions within 3 years;
7. Must have at least one extracranial measurable lesion that meets the RECIST v1.1 definition;
8. ECOG 0 or 1;
9. The toxicity of previous antineoplastic therapy has returned to ≤ grade 1 as defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. No blood transfusion is allowed within 14 days before the first use of the study drug, and no cell growth factor is allowed. The organ function level must meet the requirements;
12. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN;
13. For premenopausal women of childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum pregnancy must be negative, and the patient must not be 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. Chemotherapy, biological therapy and other anti-tumor therapies have been used within 4 weeks or 5 half-lives before the first dose; Mitomycin and nitrosoureas were administered within 6 weeks before the first dose; Oral drugs such as fluorouracil;
2. History of severe heart disease;
3. Prolonged QT interval, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
4. Active autoimmune and inflammatory diseases;
5. Other malignancies diagnosed within 5 years before the first dose;
6. Unstable thrombotic events requiring therapeutic intervention within 6 months before screening; Infusion-related thrombosis was excluded;
7. Hypertension poorly controlled by two antihypertensive drugs (systolic blood pressure \&gt; 150 mmHg or diastolic blood pressure \&gt; 100 mmHg);
8. A history of ILD requiring steroid therapy, or current ILD or radiation pneumonitis of grade ≥1 according to the RTOG/EORTC definition, or a suspicion of such disease;
9. Patients with poor glycemic control;
10. Complicated with pulmonary diseases leading to clinically severe respiratory function impairment;
11. Patients with primary central nervous system tumors or CNS metastases after failure of local treatment;
12. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of BL-M17D1's excipients;
13. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
14. Prior anthracycline therapy with more than the protocol-specified cumulative dose of an anthracycline;
15. Human immunodeficiency virus antibody positive, active tuberculosis, active hepatitis B virus infection or active hepatitis C virus infection;
16. Active infection requiring systemic therapy with a serious infection within 4 weeks prior to informed consent; There were indications of pulmonary infection or active pulmonary inflammation within 2 weeks before informed consent;
17. Patients with massive or symptomatic effusions, or poorly controlled effusions;
18. Had participated in another clinical trial within 4 weeks before the first dose;
19. Pregnant or lactating women;
20. Patients with superior vena cava syndrome should not be rehydrated;
21. A history of severe neurological or psychiatric illness;
22. Severe unhealed wounds, ulcers, or fractures within 4 weeks before signing the informed consent;
23. Subjects with clinically significant bleeding or obvious bleeding tendency within 4 weeks before signing the informed consent;
24. History of intestinal obstruction, inflammatory bowel disease or extensive bowel resection or presence of Crohn's disease, ulcerative colitis or chronic diarrhea;
25. Who are scheduled to receive live vaccine or who receive the vaccine within 28 days before the first dose;
26. The investigators did not consider it appropriate to apply other conditions for participation in the trial.

Primary outcomes:
measure: Phase Ia: Dose limiting toxicity (DLT)
timeFrame: Up to 21 days after the first dose
measure: Phase Ia: Maximum tolerated dose (MTD)
timeFrame: Up to 21 days after the first dose
measure: Phase Ib: Recommended Phase II Dose (RP2D)
timeFrame: Up to approximately 24 months
Secondary outcomes:
measure: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Cmax
timeFrame: Up to approximately 24 months
measure: Tmax
timeFrame: Up to approximately 24 months
measure: T1/2
timeFrame: Up to approximately 24 months
measure: AUC0-t
timeFrame: Up to approximately 24 months
measure: CL (Clearance)
timeFrame: Up to approximately 24 months
measure: Ctrough
timeFrame: Up to approximately 24 months
measure: ADA (anti-drug antibody)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Phase Ib: Duration of Response (DOR)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Ha'erbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
References: