A Study of BL-M07D1 in Patients With HER2-mutated, Locally Advanced or Metastatic Non-small-cell Lung Cancer

A Phase Ib/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-M07D1 for Injection in Patients With HER2 Mutated, Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)

This phase Ib/II study is designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of injectable BL-M07D1 in patients with HER2-mutated, locally advanced or metastatic non-small cell lung cancer.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: BL-M07D1

• Study Type: Interventional
• Enrollment (Estimated): 98
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sa Xiao, PHD; Phone Number: +8615013238943; Email: xiaosa@baili-pharm.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Li Zhang

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.
4. expected survival time ≥3 months.
5. Histologically or cytologically confirmed, unresectable locally advanced or metastatic non-small cell lung cancer.
6. Confirmed known HER2-sensitive mutations, investigator-confirmed previous testing results, and trial site laboratory testing results were acceptable.
7. Patients in the advanced stage who had received platinum-based chemotherapy and immunotherapy concurrent or sequential therapy were unable to tolerate standard treatment or had disease progression during or after treatment.
8. Consent to provide archived tumor tissue or fresh tissue samples from primary or metastatic sites within 2 years for biomarker testing; Participants who were unable to provide tumor tissue samples could be enrolled if they met other inclusion and exclusion criteria after evaluation by investigators.
9. Must have at least one measurable lesion according to RECIST v1.1 definition.
10. ECOG score 0 or 1.
11. Toxicity of previous antineoplastic therapy has returned to grade 1 or less as defined by NCI-CTCAE v5.0 .
12. No severe cardiac dysfunction, left ventricular ejection fraction ≥50%.
13. Organ function levels must meet the requirements.
14. Coagulation function: international normalized ratio (INR) ≤1.5, and activated partial thromboplastin time (APTT) ≤1.5ULN.
15. Urine protein ≤2+ or ≤1000mg/24h.
16. For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the start 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. Received chemotherapy, biological therapy, immunotherapy or other antitumor treatments within 4 weeks or 5 half-lives prior to the first dose (6 weeks for mitomycin and nitrosoureas; oral fluorouracil drugs, etc.).
2. Prior treatment with an ADC drug containing a camptothecin derivative (topoisomerase I inhibitor) as a toxin.
3. Presence of other gene mutations for targeted drug therapy.
4. A history of severe cardiovascular and cerebrovascular diseases.
5. Active autoimmune or inflammatory diseases.
6. Patients with other malignant tumors within 5 years before the first administration.
7. Unstable deep vein thrombosis, arterial thrombosis, and pulmonary embolism requiring medical intervention within 6 months before screening; Infusion-related thrombosis was excluded.
8. Patients with poorly controlled pericardial effusion, pleural effusion, peritoneal effusion, or pelvic effusion with clinical symptoms were judged by the investigator to be ineligible for enrollment.
9. Hypertension poorly controlled by antihypertensive drugs (systolic BP > 150 mmHg or diastolic blood pressure > 100 mmHg).
10. Current interstitial lung disease, drug-induced interstitial pneumonia, radiation pneumonitis requiring steroid therapy, or a history of these diseases.
11. Patients with central nervous system (CNS) metastases and/or carcinomatous meningitis (meningeal metastases). .
12. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any ingredient of BL-M07D1.
13. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT).
14. Human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > lower detection limit) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA > lower detection limit).
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.

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-M07D1; Participants receive BL-M07D1 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-M07D1; Administration by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase II: 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: 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-M07D1.	Up to 21 days after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Cmax	Maximum serum concentration (Cmax) of BL-M07D1 will be investigated.	Up to 21 days after the first dose
Tmax	Time to maximum serum concentration (Tmax) of BL-M07D1 will be investigated.	Up to 21 days after the first dose
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
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-M07D1. The type, frequency and severity of TEAE will be evaluated during the treatment of BL-M07D1.	Up to approximately 24 months
Progression-free Survival (PFS)	The PFS is defined as the time from the participant's first dose of BL-M07D1 to the first date of either disease progression or death, whichever occurs first.	Up to approximately 24 months
ADA (anti-drug antibody)	Frequency of anti-BL-M07D1 antibody (ADA) will be investigated.	Up to approximately 24 months
Ctrough	Ctrough is defined as the lowest serum concentration of BL-M07D1 prior to the next dose will be administered.	Up to 21 days after the first dose

Collaborators and Investigators

• Sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Li Zhang, PHD, Sun Yat-sen University

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 29, 2023
• First Submitted That Met QC Criteria: October 29, 2023
• First Posted (Actual): November 2, 2023

Study Record Updates

• Last Update Posted (Actual): August 3, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: BL-M07D1-201

Drug and device information, study documents

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