A Study of BL-M17D1 in Patients With Locally Advanced or Metastatic HER2 Positive/Lower Expression Gastrointestinal Cancer and Other Solid Tumors

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/Lower Expression Gastrointestinal Cancer and Other Solid Tumors

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 locally advanced or metastatic HER2 positive/lower expression gastrointestinal cancer and other solid tumors.

Inclusion Criteria:

1. Voluntarily sign the informed consent and follow the requirements of the protocol;
2. No gender limit;
3. Age: ≥18 years old and ≤75 years old (stage Ia); ≥18 years old (stage Ib);
4. Expected survival time ≥3 months;
5. The pathologic histology and/or cytology diagnosis of locally advanced or metastatic positive HER2 / low expression of the digestive tract tumor and other solid tumor;
6. Consent to provide archival tumor tissue samples or fresh tissue samples from primary or metastatic lesions within 2 years;
7. Must have at least one measurable lesion according to RECIST v1.1 definition;
8. ECOG 0 or 1;
9. Toxicity of previous antineoplastic therapy has returned to ≤ grade 1 defined by NCI-CTCAE v5.0;
10. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%;
11. Organ function level must meet the requirements;
12. Coagulation function: international normalized ratio ≤1.5, and activated partial thromboplastin time ≤1.5ULN;
13. Urine protein ≤2+ or ≤1000mg/24h;
14. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the initiation of treatment, serum pregnancy must be negative, and must be non-lactating; All the patients (no matter male or female) shall be 6 months after the end of the treatment period and full barrier precautions.

Exclusion Criteria:

1. Anti-tumor therapy such as chemotherapy or biological therapy has 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. QT prolongation, complete left bundle branch block, III degree atrioventricular block, frequent and uncontrollable arrhythmia;
4. Active autoimmune and inflammatory diseases;
5. Other malignant tumors diagnosed within 5 years before the first dose;
6. Hypertension poorly controlled by two antihypertensive drugs;
7. Patients with poor glycemic control before the first dose;
8. Have to hormone treatment of interstitial lung disease, or the current with ILD or suspected suffering from such diseases;
9. Complicated pulmonary diseases leading to clinically severe respiratory function impairment;
10. Patients with massive or symptomatic effusions or poorly controlled effusions;
11. Imaging examination showed that the tumor had invaded or wrapped around the chest, neck, pharynx and other large blood vessels;
12. Screening for unstable thrombotic events requiring therapeutic intervention within the preceding 6 months;
13. Patients with active central nervous system metastases;
14. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any of the excipients of BL-M17D1;
15. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation;
16. HIV antibody positive, active tuberculosis, active hepatitis B virus infection, or active hepatitis C virus infection;
17. Active infection requiring systemic therapy with serious infection within 4 weeks before informed consent; There were indications of pulmonary infection or active pulmonary inflammation within 2 weeks before informed consent;
18. 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 wound, ulcer, or fracture 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 disease Sexual diarrhea;
25. Patients scheduled for vaccination or receiving live vaccine within 28 days before the first dose;
26. Other conditions for participation in the trial were not considered appropriate by the investigator.