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

NCT06293898 · SystImmune Inc.
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Official title
A Phase 1 Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BL-M07D1 in Subjects With HER2 Expressing Advanced Malignant Solid Tumors
About this study
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. .
Eligibility criteria
Inclusion Criteria: Participants must meet all the following inclusion criteria to be eligible for participation in this study: 1. Signed the informed consent form voluntarily and agreed to follow the program requirements. 2. Either sex 3. Age: ≥18 years 4. Life expectancy of ≥3 months 5. For Dose Escalation and Dose Finding: Documented locally advanced or metastatic HER2-expressing (IHC 1+ to 3+ and/or HER2 gene amplification or activating mutation \[see Table 17-5\] in tumor specimen by ISH or 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, or whose cancer is considered refractory to the standard of care or for which no standard treatment is available, including: 1. Cohort 1: Participants with HER2 expression in endometrial cancers 2. Cohort 2: Participants with HER2 expression in cervical cancers 3. Cohort 3: Participants with HER2 expression in ovarian cancers, including fallopian tube cancer and primary peritoneal cancer 4. Cohort 4: Participants with HER2 expression in urothelial cancers 5. Cohort 5: Participants with HER2 expression in biliary tract cancers 6. Cohort 6: Participants with HER2 expression in breast cancer 7. Cohort 7: Participants with HER2 expression in lung cancer 8. Cohort 8: Participants with HER2 expression in gastric, esophageal, or gastroesophageal junction (GEJ) cancers 9. Cohort 9: Participants with HER2 expression in other solid tumors as approved by the medical monitor Note: For indications in which a HER2-directed therapy is approved, the approved treatment is recommended although not mandated, at the discretion of the investigator. 6. Agree to provide most recent existing tumor samples (formalin-fixed paraffin-embedded \[FFPE\] tissue block or slides) from primary or metastatic sites for tissue-based IHC staining to centrally determine HER2 expression (see details in Section 7.1.1). 1. In dose escalation and dose finding: archival tissue or fresh biopsy. If no archival tissue is available or it is not possible to obtain a fresh tissue biopsy, medical monitor approval is required to screen participant; 2. In dose expansion: an FFPE block or slides from fresh biopsy or the most recent archival tissue is required. 7. At least one measurable lesion based on RECIST (Response Evaluation Criteria in Solid Tumors) V1.1 8. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 9. Toxicity of previous antitumor therapy has returned to Grade ≤1 as defined by the National Cancer Institute (NCI) CTCAE V5.0, except for alopecia and endocrinopathies controlled by replacement therapy that must be Grade ≤2 10. No serious cardiac dysfunction, left ventricular ejection fraction ≥50% 11. Adequate organ function before enrollment, defined as: 1. Marrow function: Absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet (PLT) count ≥100×10\^9 /L, hemoglobin (Hb) ≥9.0 g/dL \[blood transfusion, PLT transfusion, erythropoietin, hematopoiesis agents, and granulocyte colony-stimulating factor (G-CSF) use are not allowed 1 week prior to screening\] 2. Hepatic function: Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN) (≤3×ULN for participants with Gilbert's syndrome or liver metastasis at baseline), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) without liver metastasis ≤3.0×ULN, AST and ALT with liver metastasis ≤5.0×ULN 3. Renal function: 1. In dose escalation and dose finding: Creatinine (Cr) clearance ≥50 mL/minute (Cockcroft-Gault equation) or estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m\^2 (Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] equation) 2. In dose expansion: Cr clearance ≥40 mL/minute (Cockcroft-Gault equation) or eGFR ≥40 mL/min/1.73 m\^2 (CKD-EPI equation) 12. Coagulation parameters: International Normalized Ratio (INR) ≤1.5×ULN, and activated partial thromboplastin time (aPTT) ≤1.5×ULN, unless receiving anticoagulation therapy with prothrombin time and aPTT levels within the intended therapeutic range 13. Urine protein ≤2+ or ≤1000 mg/24 hours (in dose escalation and dose finding only) 14. Sexually active fertile participants and their partners must agree to use highly effective methods of contraception (defined in Appendix D) during the course of the study and for a washout period after the last dose of study treatment (7 months for women of childbearing potential and 4 months for men). An additional contraceptive method, such as a barrier method (eg, condom), is recommended. 15. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at screening and must be nonlactating. Female participants are considered WOCBP unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman \>45 years old in the absence of other biological or physiological causes). In addition, females \<55 years old must have a serum follicle stimulating hormone (FSH) level \>40 mIU/mL to confirm menopause. NOTE: Documentation may include review of medical records, medical examination, or medical history interview by study site staff. Additional Inclusion Criteria for Dose Expansion 16. For participants with urothelial carcinoma (Part A: Randomized Doses): 1. Histologically confirmed advanced or unresectable HER2-expressing (as defined in Inclusion Criterion #5) urothelial carcinoma of the upper or lower urinary tract, not amenable to curative surgery or radiation. Mixed histological types are allowed if urothelial is the primary histology; however, small cell histology is excluded. 2. Participants with progression or recurrence following receipt of an ADC (eg, enfortumab vedotin or disitamab vedotin) and anti-PD1/PD-L1 therapy (either as a combination regimen or as separate lines of therapy) in the advanced or metastatic setting. Patients treated with enfortumab/pembrolizumab in the localized muscle invasive setting will be eligible. Prior platinum therapy is allowed but not required. Participants should have no more than 3 prior lines of systemic cytotoxic therapy (eg, ADC, chemotherapy) in the advanced or metastatic setting. 17. Multiple Indications (Part B: Basket Dosing): Has documented locally advanced or metastatic HER2-expressing (as defined in Inclusion Criterion #5) solid tumor(s) not amenable to curative surgery or radiation and has received at least 2 lines of standard therapy, including adjuvant/neoadjuvant treatment, or whose cancer is considered refractory to the standard of care or for which no standard treatment is available, including: 1. Participants with HER2 expression in endometrial cancer 2. Participants with HER2 expression in cervical cancer 3. Participants with HER2 expression in ovarian cancer, including fallopian tube cancer and primary peritoneal cancer 4. Participants with HER2 expression in breast cancer, status post-trastuzumab deruxtecan 5. Participants with HER2 expression in breast cancer, trastuzumab deruxtecan-naïve 6. Participants with HER2 expression in gastric, esophageal, or GEJ cancers 18. Participants deemed at high-risk for infection, including those with an indwelling catheter or ostomy, must be willing to receive prophylactic G-CSF during their time on study (see Section 6.3.3.5). Exclusion Criteria Participants who meet any of the following criteria will not be eligible for participation in this study: 1. Chemotherapy, biological therapy, immunotherapy, radical radiotherapy, targeted therapy (including small molecule inhibitor of tyrosine kinase), and other antitumor therapy within 4 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. Participants with history of severe heart disease, such as symptomatic congestive heart failure (CHF) ≥ Grade 2 (CTCAE 5.0), New York Heart Association (NYHA) ≥ Grade 2 heart failure at any time, or history of myocardial infarction or unstable angina pectoris within 6 months before enrollment. 3. Participants with prolonged QT interval corrected Fridericia formula (\[QTcF\]\>470 msec), complete left bundle branch block, Grade 3 atrioventricular block 4. Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory bowel disease, and Hashimoto's thyroiditis, etc. Participants with skin diseases that do not require systemic treatment (such as vitiligo, psoriasis), well-controlled type 1 diabetes, or hypothyroidism are permitted. For autoimmune conditions that are active but stable and low grade on systemic therapy, discussion with the medical monitor is required prior to screening 5. Participants with other prior malignancies except for: basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ after adequate resection, or other malignancy treated with curative intent with a disease-free interval of at least 3 years prior to screening 6. Participants with poorly controlled hypertension by 2 types of antihypertensive drugs (systolic blood pressure \>150 mmHg or diastolic blood pressure \>100 mmHg) 7. Participants with advanced or clinically significant lung diseases, such as poorly controlled chronic obstructive pulmonary disease and asthma, restrictive lung disease, pulmonary hypertension, etc. 8. Participants who have a history of noninfectious interstitial lung disease (ILD)/ pneumonitis that required treatment with steroids, have current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening 9. Participants with stroke or transient ischemic attack (TIA) within 6 months before enrollment 10. Participants with a thromboembolic event (eg, deep vein thrombosis or pulmonary embolism) within 6 months before enrollment except for those who are clinically stable and receiving treatment with adequate anticoagulant therapy for at least 3 weeks before enrollment 11. Participants 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 (\<10 mg prednisone or equivalent/day) may participate 12. Participants with pre-existing Grade ≥2 peripheral neuropathy 13. Participants who have a history of anaphylaxis or severe hypersensitivity to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-M07D1 14. Participants who are receiving treatment with systemic glucocorticoids \>10 mg/day equivalent of prednisone, except for the treatment of chronic obstructive pulmonary disease, antiemetic, infusion reactions; however, treatment with low dose glucocorticoids (≤10 mg/day equivalent of prednisone) is permitted. The chronic use of topical, inhaled, and locally injected steroids is permitted 15. Participants who have received treatment with anthracyclines with a cumulative dose exceeding 360 mg/m\^2 16. Participants with known human immunodeficiency virus (HIV) infection (HIV antibody positive). Participants who are HIV positive are allowed to participate if all the following criteria are met: 1. Undetectable HIV RNA and CD4 count ≥ 350 cells/μL at screening; 2. No AIDS-defining opportunistic infection within 12 months prior to screening; 3. On stable antiretroviral therapy (ART) for at least 4 weeks prior to enrollment with projected continuation of ART as clinically indicated while on the study. 17. Participants with active hepatitis B virus (HBV) infection (positive HBsAg test). Participants with a chronic inactive HBV infection are eligible if all the following criteria are met: 1. Have an HBV DNA viral load \< 500 IU/mL; 2. Have normal AST and ALT, OR if liver metastasis is present, have AST and ALT \<3×ULN which are not attributed to HBV infection; 3. Are on antiviral treatment, as clinically indicated. 18. Participants with active hepatitis C virus (HCV) infection (HCV antibody positive and HCV RNA \> the lower limit of detection). Participants with a positive anti-HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA 19. Participants with known active tuberculosis 20. Participants with active infections requiring IV antibiotic, antiviral, or antifungal treatment, such as severe pneumonia, bacteremia, sepsis, etc., within 1 week prior to first dose of study treatment. Participants on stable oral antimicrobials with no clinical or laboratory evidence of active infection are eligible 21. Participants who are pregnant, breastfeeding, or planning to become pregnant during the study 22. Other conditions that the investigator or sponsor believes are not suitable for participating in this clinical trial. 23. For Dose Expansion Only: Prior treatment with any topoisomerase inhibitor ADC. If the topoisomerase I ADC is sacituzumab govitecan, prior discussion with the medical monitor is required for potential inclusion
Study design
Enrollment target: 280 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-02-09
Estimated completion: 2029-04-15
Last updated: 2026-07-20
Interventions
Drug: BL-M07D1
Primary outcomes
  • Summary of safety (Though study completion, an average of 24 months)
  • 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)
Sponsor
SystImmune Inc. · industry
Contacts & investigators
ContactChristine LaRock · contact · christine.larock@systimmune.com · 425-453-6841
ContactWhitney Eakins · contact · whitney.eakins@systimmune.com · 425-453-6841
InvestigatorClinical Leader · study_director, SystImmune Inc.
All locations (17)
University of Alabama BirminghamRecruiting
Birmingham, Alabama, United States
City of HopeRecruiting
Duarte, California, United States
Cedars SinaiRecruiting
Los Angeles, California, United States
Scripps HealthNot Yet Recruiting
San Diego, California, United States
University of MiamiRecruiting
Miami, Florida, United States
Sarah Cannon Research institute - Lake Nona FloridaRecruiting
Orlando, Florida, United States
Georgia Cancer Center at Augusta UniversityRecruiting
Augusta, Georgia, United States
University of Illinois Cancer CenterRecruiting
Chicago, Illinois, United States
University of Chicago MedicineRecruiting
Chicago, Illinois, United States
Dana Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
Karmanos Cancer InstitiuteRecruiting
Detroit, Michigan, United States
NYU Langone Hospital - Long Island Investigational PharmacyRecruiting
Mineola, New York, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone HealthRecruiting
New York, New York, United States
Providence Portland Medical CenterRecruiting
Portland, Oregon, United States
Sarah Cannon Research InstituteRecruiting
Nashville, Tennessee, United States
Oncology ConsultantsRecruiting
Houston, Texas, United States
Virginia Cancer SpecialistsRecruiting
Fairfax, Virginia, United States