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

Official title

A Phase I, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activities of CS5001, an Anti-ROR1 Antibody-Drug Conjugate, Used as A Single Agent and in Combination With Systemic Therapies in Patients With Advanced Solid Tumors and Lymphomas

Overview

This is a first-in-human (FIH) study to evaluate the safety and preliminary efficacy of experimental drug CS5001 used as a single agent and in combination with systemic therapies in patients with advanced hematological and solid tumors.

Interventions

• Drug CS5001
  The dose and dosing schedule is decided by the Safety Monitoring Committee.
• Biological Rituximab
  IV infusion
• Drug Gemcitabine
  IV infusion
• Drug Oxaliplatin
  IV infusion
• Drug Lenalidomide
  PO
• Drug Cyclophosphamide
  IV infusion
• Drug Doxorubicin
  IV infusion
• Drug Vincristine
  IV infusion
• Drug Prednisone
  PO

Primary outcome measures

• Maximum Tolerated Dose (MTD) of CS5001 if any (for dose escalation part) [Time frame: About 6 months]
• Recommended Phase 2 Dose(RP2D) of CS5001 (for dose escalation part) [Time frame: About 6 months]
• Incident and severity of adverse events [Time frame: Until 90 days since the last dose of investigational product or until initiation of a new anti-cancer treatment, whichever occurs first]
• Objective Response Rate (ORR) (for dose expansion) [Time frame: Up to 2 years]

Secondary outcome measures (2)

• Concentration of CS5001 total antibody [Time frame: 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 [Time frame: Up to 30 days since the last dose of or until initiation of a new anti-cancer treatment, whichever occurs first]

Eligibility criteria

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 mono-therapy cohorts, eligible patients must have pathologically confirmed relapsed/refractory (R/R) lymphomas or advanced solid tumors, and have demonstrated failure with previous line(s) of standard-of-care treatment. Patients in the solid tumor cohort must exhibit ROR1-positive expression in their baseline tumor tissues. For combination therapy cohorts, DLBCL patients must either be treatment-naïve or have experienced failure with at least one prior line of standard-of-care therapy to qualify for treatment with CS5001 in combination with first-line or subsequent standard-of-care therapies for DLBCL. Solid tumor patients must have pathologically confirmed disease, be naïve to PD-1/PD-L1 inhibitors, and have at least failed first-line therapy or standard-of-care treatment.
• 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 0-2.
• Have adequate organ function.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 29 centers

• Anhui Provincial Cancer Hospital — Hefei
• Anhui Provincial Hospital, — Hefei
• Beijing Cancer Hospital — Beijing
• Beijing Cancer Hospital — Beijing
• Yanda Lu Dao Pei Hospital — Beijing
• The Cancer Hospital Affiliated to Chongqing University — Chongqing
• Fujian Cancer Hospital — Fuzhou
• Guangdong Province Hospital — Guangzhou
• … and 21 more centers

Australia · 6 centers

• Scientia Clinical Research Limited — Randwick
• Ashford Cancer Centre Research — Adelaide
• Central Adelaide Local Health Network Incorporated — Adelaide
• Royal Adelaide Hospital (RAH) — Adelaide
• Epworth Freemasons Medical Centre — East Melbourne
• Epworth Foundation trading as Epworth HealthCare — Melbourne

United States · 3 centers

• North Shore Hematology Oncology Associates — East Setauket
• Columbia U. - Herbert Irving Comprehensive Cancer Center — New York
• BUMC - Mary Crowley Cancer Research Centers (MCCRC) — Dallas

Identifiers

NCT: NCT05279300 · CS5001-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗