A Safety and Efficacy Study of HCB101, Fc-fusion Protein Targeting SIRPα-CD47 Pathway, in Solid or Hematological Tumors

Official title

A Phase 1, Open-label, Multi-center, Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of HCB101 in Subjects With Advanced Solid Tumors or Relapsed and Refractory Non-Hodgkin Lymphoma

Overview

The purpose of this study is to find out whether IV injection of HCB101 is an effective treatment for different types of advanced solid tumors or relapsed and refractory non-Hodgkin lymphoma and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.

Detailed description

This is an open-label, multi-center, dose-escalation, Phase 1 study. This study is to evaluate the safety, tolerability, pharmacokinetics (PK), anti-tumor activity, and identification of maximum tolerated dose (MTD) of HCB101 intravenous injection in adults with advanced solid tumors or relapsed and refractory non-Hodgkin lymphoma.

Eligible subjects must have failed standard therapies, been intolerable, or been considered medically inappropriate by the investigator. Subjects will be treated until unacceptable AEs, radiographic or clinical documented disease progression, withdrawal of consent, loss to follow-up, death, or termination of the study, whichever occurs first.

Interventions

• Drug HCB101
  HCB101 administered via. intravenous (IV) infusion.

Primary outcome measures

• Number/incidence and percentage of subjects with adverse events, including ADA. [Time frame: 12 months]
• Number of subjects with MTD of HCB101 [Time frame: 12 months]

Secondary outcome measures (8)

• Overall Rate Response (ORR) [Time frame: 12 months]
• Duration of Response (DoR) [Time frame: 12 months]
• Disease Control Rate (DCR) [Time frame: 12 months]
• Progression-Free Survival (PFS) [Time frame: 12 months]
• Peak Plasma Concentration (Cmax) of HCB101 [Time frame: 12 months]
• Area under the plasma concentration versus time curve (AUC) of HCB101 [Time frame: 12 months]
• Time to maximum drug concentration in plasma (Tmax) of HCB101 [Time frame: 12 months]
• Terminal elimination half-life (t1/2) of HCB101 [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Able to understand and willing to sign the ICF.
• Male and female subjects of ≥18 years of age.
• Histologically/cytologically confirmed, locally advanced solid tumor: subjects with histologically or cytologically confirmed advanced solid tumors refractory to standard therapy, or for which no standard treatment exists or non-Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of therapy.
• For subjects with advanced solid tumor - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
• For subjects with non-Hodgkin lymphoma - must have non-Hodgkin lymphoma that is measurable or assessable for response per Lugano Classification (with 2016 refinement).
• Must have ECOG performance status of 0 to 2 at Screening.
• Able to provide tumor tissue samples.
• Have life expectancy of ≥12 weeks.

Exclusion criteria

• With known history of hypersensitivity to any components of HCB101.
• Known active or untreated CNS metastases and/or carcinomatous meningitis.
• Have undergone a major surgery or radical radiotherapy or palliative radiotherapy or have used a radioactive drug that is not completed at least 2 weeks prior to the first dose of HCB101.
• Clinically significant cardiovascular condition.
• Any previous treatment-related toxicities which have not recovered to ≤ Grade 1 as evaluated by National Cancer Institute, Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 or baseline, except alopecia and anemia.
• With known inherited or acquired bleeding disorder or bleeding diathesis. .
• Have RBC transfusion within 4 weeks prior to Screening.
• With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
• Any investigational or approved systemic cancer therapy.
• Active use of vitamin K antagonist anticoagulant like warfarin. Use of low molecular weight heparin and factor Xa inhibitors will be permitted on case by case basis. There will be no restriction for daily aspirin ≤ 81 mg/QD.
• Have used herbal medication within 14 days prior to the first dose of HCB101.
• Have received any treatment targeting the CD47 or SIRPα pathway.
• Have other malignancies requiring treatment within 2 years prior to the first dose of HCB101.
• Participation in another clinical study with an investigational product administered in the last 14 days prior to receiving the first dose of HCB101.
• An investigational device used within 28 days prior to the first dose of HCB101.
• Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
• Known to have a history of alcoholism or drug abuse.

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• Hematology-Oncology Associates of the Treasure Coast — Port Saint Lucie
• Carolina BioOncology — Huntersville
• Greenville Hospital System University Medical Center (ITOR) — Greenville
• UT Southwestern Medical Center — Dallas

Taiwan · 3 centers

• Taipei Medical University - Shuang Ho Hospital, Ministry of Health and Welfare — New Taipei City
• National Taiwan University Hospital — Taipei
• Taipei Veterans General Hospital — Taipei

China · 1 center

• Hangzhou First People's Hospital — Hangzhou

Identifiers

NCT: NCT05892718 · HCB101-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗