Clinical trial NCT05461768: A Study of BL-M07D1 in Patients With Locally Advanced or Metastatic HER2 Positive/Low Expression Breast Cancer and Other Solid Tumors
Official title: A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Efficacy of BL-M07D1injection in Patients With Locally Advanced or Metastatic HER2-positive/Low-expression Breast Cancer and Other Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Locally Advanced or Metastatic Solid Tumor
Lead sponsor: Sichuan Baili Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: SystImmune Inc.
name: Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
First posted: 2022-07-18
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In phase Ia study, the safety and tolerability of BL-B07D1 in patients with locally advanced or metastatic HER2-positive/low-expression breast cancer and other solid tumors will be investigated to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) of BL-M07D1.

In phase Ib study, the safety and tolerability of BL-M07D1 at the phase Ia recommended dose will be further investigated, and recommended phase II dose (RP2D) for phase II clinical studies will be determined.

In addition, the preliminary efficacy, pharmacokinetic characteristics, and immunogenicity of BL-M07D1 in patients


Eligibility criteria: Inclusion Criteria:

* 1. Sign the informed consent voluntarily and follow the program requirements
* 2. No gender limitation;
* 3. Age: ≥18 years old and ≤75 years old (Stage Ia);≥18 years old (Ib);
* 4. Expected survival time ≥3 months;
* 5. Inoperable locally advanced or metastatic HER2-positive/low-expression breast cancer and other solid tumors that have been histopathologically and/or cytologically confirmed and have failed standard therapy, or are not available for standard therapy, or are not currently eligible for standard therapy; HER2 positive: IHC3+, or IHC2+ and ISH positive; HER2 low expression: IHC2+ and ISH negative, or IHC1+;
* 6. Agree to provide archived tumor tissue samples or fresh tissue samples from the primary tumor or metastatic tumor within 2 years (to detect the expression of HER2 protein in tumor pathological tissue and explore the correlation between HER2 protein and bl-M07D1 validity index); If subjects are unable to provide tumor tissue samples, they will be admitted after evaluation by the investigator if other admission criteria are met.
* 7. Must have at least one measurable lesion as defined by RECIST V1.1;
* 8. ECOG score of 0 or 1;
* 9. Toxicity of previous antitumor therapy has returned to level ≤1 as defined by NCI-CTCAE V5.0 (the investigator considered asymptomatic laboratory abnormalities, such as elevated ALP, hyperuricemia, and elevated blood glucose, etc.); Except for toxicity that the investigator judged to have no safety risk, such as alopecia, pigmentation, grade 2 peripheral neurotoxicity, etc.);
* 10. No serious cardiac dysfunction, left ventricular ejection fraction ≥50%;
* 11. Organ function level must meet the following requirements and meet the following standards: A) Bone marrow function: absolute neutrophil count (ANC) ≥1.5×10\^9/L, platelet count ≥90×10\^9/L, hemoglobin ≥90 g/L; B) Liver function: total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN in patients without liver metastasis, AST and ALT ≤5.0 ULN in patients with liver metastasis; C) Renal function: creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to the Cockcroft and Gault formula).
* 12. Coagulation function: International standardized ratio (INR) ≤1.5, and activated partial thrombin time (APTT) ≤1.5ULN;
* 13. Urinary protein ≤2+ or ≤1000mg/24h;
* 14. For premenopausal women at risk of fertility, pregnancy tests must be performed within 7 days prior to the start of treatment. Serum/urine pregnancy must be negative and must be non-lactation; All enrolled patients (male and female) should use adequate barrier contraception throughout the treatment cycle and 6 months after the end of treatment

Exclusion Criteria:

* 1. Prior use of chemotherapy, biotherapy, immunotherapy, radical radiotherapy, major surgery (as defined by the investigator), targeted therapy (including small molecule tyrosine kinase inhibitors) and other antitumor therapies within 4 weeks or 5 half-lives (whichever is less) prior to initial dosing; Mitomycin and nitrosourea were administered within 6 weeks prior to initial administration; For oral fluorouracil drugs such as gio, capecitabine, or palliative radiotherapy within 2 weeks before initial administration; The Chinese medicine with anti-tumor indication was given within 2 weeks before the first administration.
* 2. Prior ADC treatment (phase Ib only) with the toxin of camptothecin derivatives (topoisomerase I inhibitors);
* 3. History of severe heart disease, such as symptomatic congestive heart failure (CHF) grade 2 or greater (CTCAE 5.0), NYHA grade 2 or greater heart failure, history of transmural myocardial infarction, unstable angina, etc.;
* 4. QT prolongation (male QTc \> 450 msec or female QTc \> 470 msec), complete left bundle branch block, III atrioventricular block;
* 5. Active autoimmune diseases and inflammatory diseases, such as: systemic lupus erythematosus, systemic treatment of psoriasis, rheumatoid arthritis, inflammatory bowel disease, and hashimoto's thyroiditis, etc., with the exception of type I diabetes, only replacement therapy can control the hypothyroidism, no systemic treatment of skin disease (e.g., vitiligo, psoriasis);
* 6. Other malignancies diagnosed within 5 years prior to first administration, except for radical basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or radical resected carcinoma in situ;
* 7. Screening for unstable thrombotic events such as deep vein thrombosis, arterial thrombosis and pulmonary embolism requiring therapeutic intervention within the first 6 months; Infusion device-related thrombosis is excluded;
* 8. Patients with poorly controlled pleural effusion with clinical symptoms were judged by researchers to be unsuitable for inclusion;
* 9. Hypertension poorly controlled by medications (systolic \& GT; 150 mmHg or diastolic pressure \& GT; 100 mmHg);
* 10. According to CTCAE V5.0, patients were defined as ≥3 grade of lung disease, ≥2 grade of radioactive lung disease, existing or with a history of ILD;
* 11. Symptoms of active CNS metastasis. But the researchers concluded that patients with stable parenchymal metastases could be included. The definition of stability must meet the following four requirements: A. Seizureless state lasting \> 12 weeks with or without antiepileptic drugs; B. Glucocorticoids are not required; C. Two consecutive MRI scans (at least 4 weeks between scans) showed stable imaging state; D. Asymptomatic patients have been stable for more than 1 month after treatment;
* 12. Patients with a history of allergy to recombinant humanized antibody or human-mouse chimeric antibody or to any excipient component of BL-M07D1;
* 13. Prior organ transplantation or allogeneic hematopoietic stem cell transplantation (ALLO-HSCT);
* 14. Equivalent cumulative dose of doxorubicin in anthracycline adjuvant therapy was \> 360 mg/m\^2;
* 15. Positive human immunodeficiency virus antibody (HIVAb), active tuberculosis, active hepatitis B virus infection (HBV-DNA copy number \> lower limit) or active hepatitis C virus infection (HCV antibody positive and HCV-RNA \> lower limit);
* 16. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
* 17. Participated in another clinical trial within 4 weeks prior to initial administration (starting from the time of last administration);
* 18. Pregnant or nursing women;
* 19. Other conditions considered inappropriate for participation in this clinical trial by the investigator

Primary outcomes:
measure: Phase Ia: Dose limiting toxicity (DLT)
timeFrame: Up to 21 days after the first dose
measure: Phase Ia: Maximum tolerated dose (MTD)
timeFrame: Up to 21 days after the first dose
measure: Phase Ib: Phase II clinical study recommended dose (RP2D)
timeFrame: Up to 21 days after the first dose
Secondary outcomes:
measure: Treatment-Emergent Adverse Event (TEAE)
timeFrame: Up to approximately 24 months
measure: Cmax
timeFrame: Up to 21 days after the first dose
measure: T1/2
timeFrame: Up to 21 days after the first dose
measure: AUC0-t
timeFrame: Up to 21 days after the first dose
measure: Tmax
timeFrame: Up to 21 days after the first dose
measure: CL (Clearance)
timeFrame: Up to 21 days after the first dose
measure: Ctrough
timeFrame: Up to 21 days after the first dose
measure: ADA (anti-drug antibody)
timeFrame: Up to approximately 24 months
measure: Nab (neutralizing antibody)
timeFrame: Up to approximately 24 months
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: Duration of Response (DOR) Duration of Response (DOR) Duration of Response (DOR) Duration of Response (DOR) Duration of Response (DOR) Duration of Response (DOR)
timeFrame: Up to approximately 24 months
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Dongguan
country: China
facility: Dongguan People's Hospital
state: Guangdong
city: Guangdong
country: China
facility: Sun Yat-sen Memorial Hospital, Sun Yat-sen University
state: Guangzhou
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Hangzhou
country: China
facility: Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Erwei Song, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Herui Yao, PHD
role: PRINCIPAL_INVESTIGATOR
References: