Brief Title: BL-M07D1 in HER2 Expressing Malignant Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

CONDITION

• Endometrial Cancer
• Cervical Cancer
• Ovarian Cancer
• Urothelial Carcinoma
• Biliary Tract Cancer

ELIGIBILITY

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+) solid tumor(s) not amenable to curative surgery or radiation and has received at least 2 lines of standard therapy
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)

- 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. Subjects who received treatment with topoisomerase 1 inhibitors as a free form or as other formulations

- 5. Active autoimmune diseases and inflammatory diseases

- 6. Other malignant tumors diagnosed within 5 years prior to the first administration considered to be in remission

- 7. Subjects with poorly controlled hypertension by two kinds of antihypertensive drugs (systolic blood pressure >150 mmHg or diastolic blood pressure >100 mmHg)

- 8. Subjects who have Grade 3 lung disease or a history of interstitial lung disease

- 9. Deep vein thrombosis or pulmonary embolism unless under adequate anticoagulant treatment

- 10. 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. - 11. Subjects who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL M07D1 - 12. Subjects who have a history of autologous or allogeneic stem cell transplantation - 13. Has received treatment with anthracyclines with a cumulative dose exceeding 360 mg/m2 - 14. 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)

- 15. Subjects with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.

- 16. Participated in another clinical trial within 4 weeks or two half-lives (whichever is longer) prior to first dose of study treatment

- 17. Other conditions that the investigator believes are not suitable for participating in this clinical trial.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Clinical Leader

Role: Study Director

Affiliation: SystImmune Inc.

Overall Contact

Name: Elizabeth D Lotz, Tara Barrineau

Phone: 18432249830, 7045777996

Email: elizabeth.lotz@systimmune.com, tara.barrineau@systimmune.com

LOCATION