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

Registration Number
NCT05279300
Lead Sponsor
CStone Pharmaceuticals
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
480
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose escalationCS5001-
Dose expansionCS5001-
Dose expansionRituximab-
Dose expansionGemcitabine-
Dose expansionOxaliplatin-
Dose expansionLenalidomide-
Dose expansionCyclophosphamide-
Dose expansionDoxorubicin-
Dose expansionVincristine-
Dose expansionPrednisone-
Primary Outcome Measures
NameTimeMethod
Maximum Tolerated Dose (MTD) of CS5001 if any (for dose escalation part)About 6 months

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).

Recommended Phase 2 Dose(RP2D) of CS5001 (for dose escalation part)About 6 months

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.

Incident and severity of adverse eventsUntil 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)Up to 2 years

The percentage of participants with a CR or PR based on 2014 Lugano Classification Criteria for lymphomas, iwCLL 2018 guidelines for CLL/SLL and RECIST v1.1 for solid tumors.

Secondary Outcome Measures
NameTimeMethod
Concentration of CS5001 total antibodyUp to 30 days since the last dose of or until initiation of a new anti-cancer treatment, whichever occurs first
Concentration of anti-CS5001 antibodiesUp to 30 days since the last dose of or until initiation of a new anti-cancer treatment, whichever occurs first

Trial Locations

Locations (37)

Royal Adelaide Hospital (RAH)

🇦🇺

Adelaide, South Australia, Australia

Epworth Freemasons Medical Centre

🇦🇺

East Melbourne, Victoria, Australia

The Cancer Hospital Affiliated to Chongqing University

🇨🇳

Chongqing, Chongqing, China

The First Affiliated Hospital of Soochow University

🇨🇳

Suzhu, Jiang Su, China

Institute of Hematology & Blood Diseases Hospital

🇨🇳

Tianjin, Tianjin, China

North Shore Hematology Oncology Associates

🇺🇸

East Setauket, New York, United States

Columbia U. - Herbert Irving Comprehensive Cancer Center

🇺🇸

New York, New York, United States

BUMC - Mary Crowley Cancer Research Centers (MCCRC)

🇺🇸

Dallas, Texas, United States

Scientia Clinical Research Limited

🇦🇺

Randwick, New South Wales, Australia

Ashford Cancer Centre Research

🇦🇺

Adelaide, South Australia, Australia

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Royal Adelaide Hospital (RAH)
🇦🇺Adelaide, South Australia, Australia
Pratyush Kumar Giri
Contact
618 7074 4133
pratyush.giri@sa.gov.au

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