Clinical trial NCT05385692: A Study of BL-M02D1 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors or Other Solid Tumors
Official title: Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of Injectable BL-M02D1 in Patients With Locally Advanced or Metastatic Gastrointestinal Tumors or Other Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Locally Advanced or Metastatic Digestive Tract Tumors
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: 2022-05-23
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: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: In phase Ia study, the safety and tolerability of BL-M02D1 in patients with locally advanced or metastatic gastroenteric tumor or other solid tumors will be investigated to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) of BL-M02D1.

In phase Ib study, the safety and tolerability of BL-M02D1 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-M02D1 in patients with locally advanced or metastatic gastroenteric tumor or other solid tumors will be evaluated.


Eligibility criteria: Inclusion Criteria:

1. Participants must sign the informed consent form voluntarily and follow the plan requirements.
2. No gender limit.
3. Age: ≥18 years old and ≤75 years old (phase Ia); ≥18 years old (phase Ib).
4. Expected survival time ≥ 3 months.
5. Locally advanced or metastatic gastrointestinal tumor and other solid tumor confirmed by histopathology and/or cytology, which are incurable or currently without standard treatment.
6. Agree to provide archived tumor tissue samples or fresh tissue samples from the primary tumor or metastatic tumor within 2 years (TROP2 protein expression in tumor pathological tissue to explore the correlation between TROP2 protein expression and bl-M02D1 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. Participants must have at least one measurable lesion that meets the definition of RECIST v1.1 in phase Ib.
8. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1
9. Toxicity of previous antitumor therapy has returned to ≤ level 1 as defined by NCI-CTCAE v5.0 (except for asymptomatic laboratory abnormalities considered by the investigators, such as elevated ALP, hyperuricemia, and elevated blood glucose; Toxicities with no safety risk were excluded, such as alopecia, hyperpigmentation, and grade 2 peripheral neurotoxicity. Or decreased hemoglobin except ≥90 g/L).
10. Has adequate organ function before registration, defined as: a) Bone marrow function: Absolute neutrophil count (ANC) ≥1.5×109/L, Platelet count ≥90×109/L, Hemoglobin ≥90 g/L; B) Hepatic function: Total bilirubin (TBIL≤1.5 ULN), AST and ALT ≤2.5 ULN for participants without liver metastasis, AST and ALT ≤5.0 ULN for liver metastases; c) Renal function: Creatinine (Cr) ≤1.5 ULN, or creatinine clearance (Ccr) ≥50 mL/min (according to the Cockcroft and Gault formula).
11. Coagulation function: International normalized ratio (INR)≤1.5×ULN, and activated partial thromboplastin time (APTT)≤1.5ULN.
12. Urinary protein ≤2+ or ≤1000mg/24h.
13. 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 must be negative and must be non-lactating. Adequate barrier contraceptive measures should be taken during the treatment and 6 months after the end of treatment for all participants (regardless of male or female).

Exclusion Criteria:

Patients screened for any of the following conditions will not be included in this study:

1. Antitumor therapy such as chemotherapy, biotherapy, immunotherapy, radical radiotherapy, major surgery (as defined by the investigators), and targeted therapy (including small-molecule tyrosine kinase inhibitors) within 4 weeks prior to initial administration or within 5 half-lives, whichever is shorter; Mitomycin and nitrosourea were administered within 6 weeks before the first administration; Oral fluorouracil drugs such as Tizio, capecitabine, or palliative radiotherapy within 2 weeks before first administration; Traditional Chinese medicines with anti-tumor indications were administered within 2 weeks before the first dose.
2. Prior treatment with ADC drugs targeting TROP2 or ADC drugs using camptothecin derivatives (topoisomerase I inhibitors) as toxins.
3. 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, history of transmural myocardial infarction, unstable angina pectoris, Left ventricular ejection fraction \< 50% etc.
4. Participants with prolonged QT interval (male QTc\> 450 msec or female QTc\> 470 msec), complete left bundle branch block, III grade atrioventricular block.
5. 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., except for type I diabetes, hypothyroidism that can be controlled only by alternative treatment, and skin diseases that do not require systemic treatment (such as vitiligo, psoriasis).
6. The presence of a second primary tumor within 5 years prior to initial 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. Participants with poorly controlled hypertension by antihypertensive drugs (systolic blood pressure\>150 mmHg or diastolic blood pressure\>100 mmHg).
10. Lung disease defined as grade ≥3 according to CTCAE V5.0; ≥2 grade of radioactive lung disease, current or history of interstitial lung disease (ILD).
11. Symptoms of active central nervous system metastasis. However, participants with stable brain metastasis can be included. Stable is defined as: a. With or without antiepileptic drugs, the seizure-free state lasts for more than 12 weeks; b. There is no need to use glucocorticoids; c. Continuous multiple MRI (scanning interval at least 8 weeks) showed a stable state in imaging; d. Stable after treatment for more than 1 month without symptoms;
12. Participants who have a history of allergies to recombinant humanized antibodies or human-mouse chimeric antibodies or any of the components of BL-M02D1.
13. Participants have a history of organ transplantation or allogeneic stem cell transplantation (Allo-HSCT).
14. In the adjuvant (or neoadjuvant) treatment of anthracyclines, the cumulative dose of anthracyclines is\> 360 mg/m2.
15. 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).
16. Participants with active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.
17. Participated in another clinical trial within 4 weeks prior to participating in the study.
18. Pregnant or nursing women.
19. Other conditions that the investigator believes that it is not suitable for participating in this clinical trial.

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: Recommended Phase II 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: Tmax
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: 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)
timeFrame: Up to approximately 24 months
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Ruihua Xu
role: PRINCIPAL_INVESTIGATOR
References: