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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Esophageal Cancer; Solid Tumor
• Intervention / Treatment: Drug: BL-M17D1

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: 15013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Principal Investigator: Ruihua Xu
      • Principal Investigator: Feng Wang
      • Contact: Ruihua Xu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BL-M17D1; Participants receive BL-M17D1 as intravenous infusion for the first cycle (3 weeks). Participants with clinical benefit could receive additional treatment for more cycles. The administration will be terminated because of disease progression or intolerable toxicity occurring or other reasons.	Drug: BL-M17D1; Administration by intravenous infusion for a cycle of 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ia: Dose limiting toxicity (DLT)	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.	Up to 21 days after the first dose
Phase Ia: Maximum tolerated dose (MTD)	MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .	Up to 21 days after the first dose
Phase Ib: Recommended Phase II Dose (RP2D)	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.	Up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-t	AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.	Up to approximately 24 months
Phase Ib: Objective Response Rate (ORR)	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.	Up to approximately 24 months
Phase Ib: Disease Control Rate (DCR)	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]).	Up to approximately 24 months
Phase Ib: Duration of Response (DOR)	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.	Up to approximately 24 months
Treatment-Emergent Adverse Event (TEAE)	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.	Up to approximately 24 months
Cmax	Maximum serum concentration (Cmax) of BL-M17D1 will be investigated.	Up to approximately 24 months
Tmax	Time to maximum serum concentration (Tmax) of BL-M17D1 will be investigated.	Up to approximately 24 months
T1/2	Half-life (T1/2) of BL-M17D1 will be investigated.	Up to approximately 24 months
CL (Clearance)	CL in the serum of BL-M17D1 per unit of time will be investigated.	Up to approximately 24 months
Ctrough	Ctrough is defined as the lowest serum concentration of BL-M17D1 prior to the next dose will be administered.	Up to approximately 24 months
ADA (anti-drug antibody)	Frequency of anti-BL-M17D1 antibody (ADA) will be investigated.	Up to approximately 24 months

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Collaborators: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Ruihua Xu, Sun Yat-sen University; Principal Investigator: Feng Wang, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: July 8, 2024
• First Submitted That Met QC Criteria: July 8, 2024
• First Posted (Actual): July 15, 2024

Study Record Updates

• Last Update Posted (Estimated): September 18, 2025
• Last Update Submitted That Met QC Criteria: September 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Pancreatic Diseases; Colonic Diseases; Esophageal Diseases; Stomach Neoplasms; Colorectal Neoplasms; Esophageal Neoplasms; Pancreatic Neoplasms
• Other Study ID Numbers: BL-M17D1-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No