A Study of CS5001 in Patients With Advanced Solid Tumors and Lymphomas

Study Overview
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Brief Summary
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This is a first-in-human (FIH) study to evaluate the safety and preliminary efficacy of experimental drug CS5001 in patients with advanced hematological and solid tumors.

Official Title
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A Phase I, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activities of CS5001, an Anti-ROR1 Antibody Drug Conjugate, in Patients With Advanced Solid Tumors and Lymphomas

Conditions
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Advanced Solid Tumor, Advanced Lymphoma

Intervention / Treatment
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* Drug: CS5001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For solid tumor patients of dose escalation, they must have pathologically confirmed, unresectable advanced solid tumor with disease progression on or after at least 1 line of prior systemic therapy. For Lymphoma patients of dose escalation, they must have pathologically confirmed Hodgkin and non-Hodgkin B-cell lymphoma as defined per 2016 World Health Organization(WHO) classification, with disease progression on or after at least 2 lines of prior systemic therapy. For dose expansion, pathologically confirmed Mantle Cell Lymphoma(MCL, following at least two prior lines of systemic therapy including Bruton Tyrosine Kinase inhibitors), Diffuse Large B Cell Lymphoma(DLBCL, following at least two prior lines of systemic therapies), and Triple Negative Breast Cancer(TNBC, following at least 2 lines of systemic therapy for advanced disease) will be enrolled. For dose escalation, with at least one evaluable lesion as defined per Response Evaluation Criteria in Solid Tumours(RECIST) v1.1 solid tumor or per 2014 Lugano Classification Criteria for lymphoma, respectively. For dose expansion, with at least one measurable lesion as defined per RECIST v1.1 solid tumor or per 2014 Lugano Classification Criteria for lymphoma, respectively. Life expectancy > 3 months. Eastern Cooperative Oncology Group(ECOG) performance status 0 or 1. Have adequate organ function. Is willing to provide tumor tissue and control blood sample. Female subjects of childbearing potential must have a negative serum pregnancy test. Both male and female subjects must be willing to use adequate contraception. Exclusion Criteria: Has disease that is suitable for local treatment administered with curative intent. For lymphoma, candidacy for hematopoietic stem cell transplantation based on the Investigator's judgment. Has a history of a second malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured. For dose expansion: Participation in other studies involving therapies targeting ROR1 prior to study entry and/or during study participation. Has known central nervous system (CNS) lymphoma or solid tumor CNS metastasis that is either symptomatic, untreated, or requires therapy. Has other acute or chronic medical or psychiatric conditions. Has a diagnosis of immunodeficiency, or has an active autoimmune disease or other conditions that require systemic steroid therapy. Has peripheral edema, pericardial effusion, or ascites indicated for medical intervention or limiting activity of daily life. Or with a known history of peripheral vasculopathies. Patients with any active infections requiring systemic therapy within 2 weeks prior to the administration of the first dose of the study drug. Patients known to be human immunodeficiency virus (HIV)-positive or have acquired immune deficiency syndrome (AIDS). Significant cardiovascular disease within 6 months prior to the first dose of the study drug. Significant screening electrocardiogram (ECG) abnormalities. Has received major surgery, chemotherapy, definitive radiotherapy, target therapy, immunotherapy, or other anti-cancer therapy within 21 days prior to the administration of the first dose of the study drug. Administration of a live vaccine within 28 days prior to the administration of the first dose of the study drug. Has active graft versus host disease. With known active alcohol or drug abuse. Women who are pregnant or breastfeeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br> | Drug: CS5001<br>* CS5001 will be administered every 3 weeks (21 days) by intravenous (IV) infusion, and 3 weeks (21 days) is considered as one treatment cycle.<br>|
| Experimental: Dose expansion<br> | Drug: CS5001<br>* CS5001 will be administered every 3 weeks (21 days) by intravenous (IV) infusion, and 3 weeks (21 days) is considered as one treatment cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of CS5001 if any (for dose escalation part) | Participants will receive CS5001 for injection once every three weeks. The MTD will be determined by the number of participants who experience a dose limiting toxicity (DLT). | About 6 months | 
| Recommended Phase 2 Dose(RP2D) of CS5001 (for dose escalation part) | The selection of RP2D will be based on consideration of overall safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data. The RP2D may be the MTD or may be a lower dose within the tolerable dose range. | About 6 months | 
| Incident and severity of adverse events |  | Until 90 days since the last dose of investigational product or until initiation of a new anti-cancer treatment, whichever occurs first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of CS5001 total antibody, prodrug and the free cytotoxin |  | Up to 30 days since the last dose of or until initiation of a new anti-cancer treatment, whichever occurs first | 
| Concentration of anti-CS5001 antibodies |  | Up to 30 days since the last dose of or until initiation of a new anti-cancer treatment, whichever occurs first |