An Engineered Sirpα Fused to Anti-Pd-L1 And Tgf-β Fusion Protein (HCB301) in Subjects With Selected Advanced Tumors

Official title

A Phase 1, Open-label, Multicenter, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of HCB301 in Subjects With Advanced Solid Tumors or Relapsed and Refractory cHL

Overview

The purpose of this study is to find out whether IV injection of HCB301 is an effective treatment for different types of advanced solid tumors and relapsed and refractory classical Hodgkin lymphomas and what side effects (unwanted effects) may occur in subjects aged 18 years old and above.

Detailed description

This is a phase 1, open-label, multicenter, dose-escalation study. This study is to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary efficacy, and identification of maximum tolerated dose (MTD) of HCB301 intravenous injection in adults with advanced solid tumors or relapsed and refractory classical Hodgkin lymphomas.

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 HCB301
  HCB301 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 and RDE of HCB301. [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 HCB301 [Time frame: 12 months]
• Area under the plasma concentration versus time curve (AUC) of HCB301 [Time frame: 12 months]
• Time to maximum drug concentration in plasma (Tmax) of HCB301 [Time frame: 12 months]
• Terminal elimination half-life (t1/2) of HCB301 [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

• Able to understand and be willing to sign the ICF.
• Male and female subjects of ≥18 years of age.
• Histologically/cytologically confirmed, locally advanced solid tumor:

subjects confirmed advanced solid tumors who have relapsed or refractory and should have no options for standard or approved therapies known to potentially confer clinical benefit or classical Hodgkin lymphoma, relapsed or refractory to at least 2 prior lines of systemic therapy.

• For subjects with advanced solid tumors - must have at least 1 measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 at baseline.
• For subjects with classical Hodgkin lymphoma - must have classical Hodgkin lymphoma that is measurable or assessable for response.
• Must have ECOG performance status of 0 to 1 at Screening.
• Able to provide tumor tissue samples.
• Have a life expectancy of ≥12 weeks.

Exclusion criteria

• With known history of hypersensitivity to any components of HCB301.
• Known active or untreated CNS metastases and/or carcinomatous meningitis.
• Have undergone a major surgery or radical radiotherapy within 28 days or palliative radiotherapy within 14 days or have used a radioactive drug within 56 days prior to the first dose of HCB301.
• 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 administered within 21 days or 5 half-lives, whichever is shorter, before the first dose of the study drug.
• 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 ≤ 100 mg/QD.
• Have used herbal medication within 14 days prior to the first dose of HCB301.
• Have received any treatment targeting the SIRPα-CD47, PD-L1, or TGF-β pathway.
• Have other malignancies requiring treatment within 2 years prior to the first dose of HCB301.
• An investigational device used within 28 days prior to the first dose of HCB301.
• 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

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 5 centers

• The First Affiliated Hospital, Zhejiang University School of Medicine — Hangzhou
• Zhejiang Provincial Cancer Hospital — Hangzhou
• Xuzhou Central Hospital — Xuzhou
• Yantai Yuhuangding Hospital — Yantai
• Southern Medical University Zhujiang Hospital — Zhujiang

United States · 1 center

• Prisma Health-Upstate — Greenville

Taiwan · 1 center

• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City

Identifiers

NCT: NCT06487624 · HCB301-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗