Evaluation of SYS6005 in Patients With Advanced Malignant Tumor

CSPC Megalith Biopharmaceutical Co.,Ltd.

Status and phase: Enrolling; Phase 1

Conditions: B-cell Malignancies

Treatments: Drug: SYS6005

Study type: Interventional

Funder types: Industry

Identifiers

NCT06958679

SYS6005-001

Details and patient eligibility

About

This Phase I, open-label, multicenter study evaluates the safety, tolerability, pharmacokinetics, and preliminary efficacy of SYS6005 in advanced malignancies, comprising dose-escalation and expansion phases. The escalation phase employs a BOIN design with accelerated titration across seven dose levels, featuring a 21-day DLT observation period in Cycle 1, with dose adjustments guided by a Safety Monitoring Committee. The expansion phase further assesses 1-2 selected doses in three disease cohorts (diffuse large B-cell lymphoma, mantle cell lymphoma and chronic lymphocytic leukaemia/small lymphocytic lymphoma; ≤30 patients/cohort). Treatment continues until disease progression, unacceptable toxicity, or other discontinuation criteria. Safety monitoring includes AEs, labs, and ECOG PS, while efficacy is assessed via imaging. PK and immunogenicity samples are collected, and survival is tracked quarterly until death or study end. The study aims to determine the maximum tolerance dose (MTD)/recommended phase 2 dose (RP2D) and characterize SYS6005's clinical profile.

Enrollment: 132 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Participants who are voluntarily enrolled in this study and sign the informed consent form (ICF);
2. Age ≥ 18 years old, male or female;
3. Participants with cytologically or histologically confirmed advanced malignant tumor, including CLL/SLL, DLBCL, MCL, folicular lymphoma ( FL), marginal zone lymphoma ( MZL), or richter transformation lymphoma (RTL), that have failed prior standard of care, or are intolerant to standard of care;
4. Participants with at least one measurable lesion, defined as ≥1 lymph node with the longest diameter >1.5 cm or ≥1 extranodal lesion with the longest diameter >1.0 cm, and with one measurable perpendicular dimension;
5. Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0-2;
6. Expected survival ≥ 3 months;
7. Participants must have adequate organ function and have not received transfusion, erythropoietin, granulocyte colony-stimulating factor, or other medical supportive treatments within 14 days prior to examination
8. All participants must agree to undergo bone marrow aspiration during the screening period to collect tumor samples for biomarker analysis;
9. Male and female participants of childbearing potential must agree to use effective contraception from the time of signing the ICF until at least 6 months after the last dose of the investigational product; female participants of childbearing potential must have a negative pregnancy test result within 7 days prior to the first administration of the investigational product;
10. Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Exclusion criteria

1. Participants who have participated in other studies involving ROR1-targeted therapies prior to enrollment in this study, or have previously received ADC treatments containing MMAE payloads;
2. Participants with known central nervous system (CNS) lymphoma or CNS metastases from solid tumors that are symptomatic, untreated, or require treatment. Except for participants with metastases to CNS that have been completely resected and/or have stabilized or improved after radiotherapy, provided that imaging examinations prior to screening show stable disease for at least 4 weeks, and there is no evidence of brain oedema and no requirement for corticosteroids or anticonvulsant drugs;
3. Participants deemed suitable for CAR-T therapy or hematopoietic stem cell transplant (HSCT) by the investigator. Participants who have received an allogeneic haematopoietic stem cell transplant within 6 months prior to the first administration of the investigational product, have received an autologous haematopoietic stem cell transplant within 100 days prior to the first administration of the investigational product, or have received CAR-T cell therapy within 3 months prior to the first administration of the investigational product. Participants with active graft versus host disease;
4. Participants with peripheral oedema, pericardial effusion, pleural effusion, or ascites that require medical intervention or limit daily life activities;
5. Participants with records of cerebrovascular events, angina unstable, myocardial infarction, or a history of NYHA Class III-IV cardiac symptoms within 6 months before the first administration of the investigational product, or a QTcF > 450 ms recorded in three repeated ECG examinations during screening;
6. Participants with any active infection requiring systemic treatment within 2 weeks prior to the first dose of investigational product;
7. Participants who have used strong inhibitors or inducers of CYP3A4 within 7 days prior to the first dose of the investigational product, or are expected to require the use of strong inhibitors or inducers of CYP3A4 during the study treatment;
8. Participants with the severity of any toxicities from prior treatments or surgery (excluding ≤ Grade 2 alopecia, endocrine disorders manageable with hormone replacement therapy, or other toxicities that the investigator considers do not pose a safety risk to the patient) has not returned to baseline or ≤ Grade 1 per NCI-CTCAE Version 5.0;
9. Participants with ≥ grade 2 peripheral neuropathy at baseline;
10. Participants who have received major surgery, radical radiotherapy, antibody-based targeted therapy, or immunotherapy within 28 days prior to the first administration of the investigational product, or who have received palliative radiation, chemotherapy, or small molecule targeted therapy within 14 days prior to the study treatment. Participants who have used anti-tumor Chinese herbal preparations or Chinese patent medicines within 14 days prior to the first administration of the investigational product; 11: Participants with history of immunodeficiency or positive human immunodeficiency virus (HIV) antibody test during screening; 12: Participants with active hepatitis B or hepatitis C, where active hepatitis B is defined as HBsAg positive and HBV DNA > 2000 IU/ml; active hepatitis C is defined as HCV antibody positive and HCV RNA > ULN; 13: Participants who have received a live vaccine within 28 days prior to the first dose of investigational product; 14: Participants with history of hypersensitivity or atopic reactions to excipients of the investigational product or any monoclonal antibodies; 15: Women who are pregnant or breastfeeding; 16: Other situations that may interfere with the participant's participation in the study program or are not in the participant's best interest or affect the study results include: history of mental illness, addiction or drug abuse, any other clinically significant illness or condition, etc.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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132 participants in 1 patient group

Dose escalation and Dose expansion

Experimental group

Description:

Participants will receive escalating doses of SYS6005 intravenously (IV) on Day 1 of each 21-day cycle in dose escalation phase and will receive selected doses of SYS6005 intravenously (IV) on Day 1 of each 21-day cycle in dose expansion phase

Treatment:

Drug: SYS6005