Clinical trial NCT06487624: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Refractory Hodgkin Lymphoma
Keywords: Immunotherapy
CD47
PD-L1
TGF-beta
Tumor
Cancer
Lead sponsor: FBD Biologics Limited
Sponsor class: INDUSTRY
First posted: 2024-07-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: Inclusion Criteria:

1. Able to understand and be willing to sign the ICF.
2. Male and female subjects of ≥18 years of age.
3. 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.
4. 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.
5. For subjects with classical Hodgkin lymphoma - must have classical Hodgkin lymphoma that is measurable or assessable for response.
6. Must have ECOG performance status of 0 to 1 at Screening.
7. Able to provide tumor tissue samples.
8. Have a life expectancy of ≥12 weeks.

Exclusion Criteria:

1. With known history of hypersensitivity to any components of HCB301.
2. Known active or untreated CNS metastases and/or carcinomatous meningitis.
3. 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.
4. Clinically significant cardiovascular condition.
5. 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.
6. With known inherited or acquired bleeding disorder or bleeding diathesis. .
7. Have RBC transfusion within 4 weeks prior to Screening.
8. With a previously documented diagnosis of hemolytic anemia or Evans Syndrome in the last 3 months.
9. 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.
10. 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.
11. Have used herbal medication within 14 days prior to the first dose of HCB301.
12. Have received any treatment targeting the SIRPα-CD47, PD-L1, or TGF-β pathway.
13. Have other malignancies requiring treatment within 2 years prior to the first dose of HCB301.
14. An investigational device used within 28 days prior to the first dose of HCB301.
15. Positive for hepatitis B, active hepatitis C infections, positive for HIV, or known active or latent tuberculosis.
16. Known to have a history of alcoholism or drug abuse.

Primary outcomes:
measure: Number/incidence and percentage of subjects with adverse events, including ADA.
timeFrame: 12 months
measure: Number of subjects with MTD and RDE of HCB301.
timeFrame: 12 months
Secondary outcomes:
measure: Overall Rate Response (ORR)
timeFrame: 12 months
measure: Duration of Response (DoR)
timeFrame: 12 months
measure: Disease Control Rate (DCR)
timeFrame: 12 months
measure: Progression-Free Survival (PFS)
timeFrame: 12 months
measure: Peak Plasma Concentration (Cmax) of HCB301
timeFrame: 12 months
measure: Area under the plasma concentration versus time curve (AUC) of HCB301
timeFrame: 12 months
measure: Time to maximum drug concentration in plasma (Tmax) of HCB301
timeFrame: 12 months
measure: Terminal elimination half-life (t1/2) of HCB301
timeFrame: 12 months
Other outcomes:
measure: CD47 receptor occupancy on circulating red blood cells (RBCs)
timeFrame: 12 months
measure: Concentration of potential PD biomarkers in participants will be assess.
timeFrame: 12 months
measure: ctDNA detection
timeFrame: 12 months
Locations:
city: Greenville
country: United States
facility: Prisma Health-Upstate
state: South Carolina
Study officials:
References: