Open Label Study to Evaluate BL-M07D1 in HER2 Expressing Malignant Solid Tumors

Phase 1

Recruiting

• Conditions: Endometrial Cancer; Cervical Cancer; Urothelial Carcinoma; Ovarian Cancer; Gastroesophageal-junction Cancer; Esophageal Cancer; Lung Cancer; Biliary Tract Cancer; Breast Cancer; Gastric Cancer
• Interventions: Drug: BL-M07D1

• Registration Number: NCT06293898
• Lead Sponsor: SystImmune Inc.

Brief Summary

The objective of this study is to evaluate the safety, tolerability, and efficacy of BL-M07D1 in patients with HER2 expressing advanced tumors.

Detailed Description

BL-M07D1-ST-101 is a global, multi-center, Phase 1 study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of BL-M07D1 in participants with HER2 expressing advanced malignant solid tumors.

This study will be conducted in three parts (dose escalation, dose finding and dose expansion). Dosing will be conducted on Day 1 of a continuous 21-day treatment cycle. .

Study Timeline

• Study Start: 2024-02-09
• Study First Submitted: 2024-02-22
• Study First Submitted QC: 2024-03-01
• Study First Posted: 2024-03-05
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-19
• Last Update Posted: 2024-07-22
• Primary Completion: 2025-08-24
• Study Completion: 2027-08-24

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 280

Inclusion Criteria

1. Age: ≥18 years

2. Has a life expectancy of ≥3 months

3. Has documented locally advanced or metastatic HER2-expressing (IHC 1+ to 3+ and/or HER2 gene amplification in tumor specimen or in circulating tumor cells by ISH, NGS, or ctDNA-NGS) solid tumor(s) not amenable to curative surgery or radiation and has received at least 2 lines of standard therapy, including adjuvant/neoadjuvant treatment, with documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease and have progressed or refractory to standard of care, including:

   1. Cohort 1: Subjects with HER2 expression in endometrial cancers (EC)
   2. Cohort 2: Subjects with HER2 expression in cervical cancers (CC)
   3. Cohort 3: Subjects with HER2 expression in ovarian cancers (OC)
   4. Cohort 4: Subjects with HER2 expression in urothelial cancers (UC)
   5. Cohort 5: Subjects with HER2 expression in biliary tract cancers (BTC)
   6. Cohort 6: Subjects with HER2 expression in breast cancer (BC)
   7. Cohort 7: Subjects with HER2 expression in lung cancer (LC)
   8. Cohort 8: Subjects with HER2 expression in gastric, esophageal, or gastroesophageal junction (GEJ) cancers

4. Agree to provide existing tumor samples

5. Has at least one measurable lesion based on RECIST (Response Evaluation Criteria in Solid Tumors) V1.1

6. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1

7. Toxicity of previous antitumor therapy has returned to Grade ≤1

8. Has no serious cardiac dysfunction, left ventricular ejection fraction ≥50%

9. Has adequate organ function before registration

10. Coagulation function: international normalized ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (APTT) ≤1.5 ULN

11. Urinary protein ≤2+ or ≤1000 mg/24 hours

12. For premenopausal women with childbearing potential, a pregnancy test must be taken within 7 days prior to the start of treatment. Serum or urine pregnancy test must be negative and subject must be nonlactating.

13. Must agree to use adequate contraceptive measures during the treatment and for 6 months after the end of treatment for all subjects (regardless of gender)

Exclusion Criteria

1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other antitumor therapy within 2 weeks or 5 half-lives (whichever is shorter) prior to the first administration; major surgery within 4 weeks prior to the first administration; mitomycin and nitrosoureas treatment within 6 weeks prior to the first administration
2. Subjects with history of severe heart disease
3. Subjects with prolonged QT interval (QTc >470 msec), complete left bundle branch block, Grade 3 atrioventricular block
4. Active autoimmune diseases and inflammatory diseases
5. Other malignant tumors diagnosed within 5 years prior to the first administration considered to be in remission
6. Subjects with poorly controlled hypertension by two kinds of antihypertensive drugs (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg)
7. Subjects who have Grade 3 lung disease or a history of interstitial lung disease
8. Deep vein thrombosis or pulmonary embolism unless under adequate anticoagulant treatment
9. Patients with primary tumors in the central nervous system (CNS) and active or untreated CNS metastases and/or carcinomatous meningitis should be excluded. Patients with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks and have no evidence of new or enlarging brain metastases and no requirements for corticosteroids 14 days prior to dosing with the investigational product (IP). Patients on low dose corticosteroids (<20 mg prednisone or equivalent/day) may participate.
10. Subjects who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL M07D1
11. Subjects who have a history of autologous or allogeneic stem cell transplantation
12. Has received treatment with anthracyclines with a cumulative dose exceeding 360 mg/m2
13. Known human immunodeficiency virus antibody (HIVAb) positive, active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number > the lower limit of detection) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA > the lower limit of detection)
14. Subjects with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
15. Participated in another clinical trial within 4 weeks or two half-lives (whichever is longer) prior to first dose of study treatment
16. Other conditions that the investigator believes are not suitable for participating in this clinical trial.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
BL-M07D1 administered Day 1 of a 21-day cycle	BL-M07D1	-

Primary Outcome Measures

Name	Time	Method
To determine the maximum tolerated dose (MTD) if reached or maximum administered dose (MAD) and two or more recommended doses for dose expansion (RDEs) of BL-M07D1	21 Days	Determine the highest BL-M07D1 dose level at which subjects do not experience a DLT during the DLT evaluation period and highest BL-M07D1 dose administered in the event and MTD cannot be defined.
Summary of safety	Though study completion, an average of 24 months	The number of patients with dose-limiting toxicities, serious adverse events, treatment-emergent adverse events, physical exam findings, vital signs, laboratory tests, ECG parameters and echocardiograph

Trial Locations

Locations (2)

SystImmune Recruiting Center; 🇺🇸 Fairfax, Virginia, United States

SystImmune Recruiting Site; 🇺🇸 Houston, Texas, United States