Colorectal Cancer, Esophageal Cancer, Gastric Cancer, Pancreatic Cancer, Solid Tumor
Conditions
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 locally advanced or metastatic HER2 positive/lower expression gastrointestinal cancer and other solid tumors.
Interventions
DRUGBL-M17D1
Administration by intravenous infusion for a cycle of 3 weeks.
Sponsors
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Sichuan Baili Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ia: Dose limiting toxicity (DLT) | Up to 21 days after the first dose | DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration. |
| Phase Ia: Maximum tolerated dose (MTD) | Up to 21 days after the first dose | MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle . |
| Phase Ib: Recommended Phase II Dose (RP2D) | Up to approximately 24 months | The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of BL-M17D1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T1/2 | Up to approximately 24 months | Half-life (T1/2) of BL-M17D1 will be investigated. |
| AUC0-t | Up to approximately 24 months | AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration. |
| CL (Clearance) | Up to approximately 24 months | CL in the serum of BL-M17D1 per unit of time will be investigated. |
| Ctrough | Up to approximately 24 months | Ctrough is defined as the lowest serum concentration of BL-M17D1 prior to the next dose will be administered. |
| Treatment-Emergent Adverse Event (TEAE) | Up to approximately 24 months | TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of BL-M17D1 . The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M17D1. |
| Phase Ib: Objective Response Rate (ORR) | Up to approximately 24 months | ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1. |
| Phase Ib: Disease Control Rate (DCR) | Up to approximately 24 months | The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]). |
| Phase Ib: Duration of Response (DOR) | Up to approximately 24 months | The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first. |
| ADA (anti-drug antibody) | Up to approximately 24 months | Frequency of anti-BL-M17D1 antibody (ADA) will be investigated. |
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) of BL-M17D1 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of BL-M17D1 will be investigated. |
Countries
China
Contacts
Primary ContactSa Xiao, PHD
Outcome results
None listed