Clinical Trials /

A Phase 1 Study of HS130 in Combination With Viagenpumatucel-L (HS110) in Patients With Solid Tumors

NCT04116710

Description:

This is a phase 1 open-label, single center, dose escalation study to determine a safe and effective maximum tolerated dose of HS-130 in combination with viagenpumatucel-L (HS-110) for adult subjects with advanced solid tumors who are refractory to Standard of Care.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study of HS130 in Combination With Viagenpumatucel-L (HS110) in Patients With Solid Tumors
  • Official Title: A Phase I, First-in-human, Dose-escalation Study to Evaluate the Safety and Immunologic Response After Administration of HS-130 in Combination With HS-110 (Viagenpumatucel-L) in Patients With Solid Tumors Refractory to Standard Care

Clinical Trial IDs

  • ORG STUDY ID: HS130-001
  • NCT ID: NCT04116710

Conditions

  • Advanced Solid Tumor

Interventions

DrugSynonymsArms
HS-110 (viagenpumatucel-L)Phase 1: HS-130 + HS-110 (viagenpumatucel-L)
HS-130Phase 1: HS-130 + HS-110 (viagenpumatucel-L)

Purpose

This is a phase 1 open-label, single center, dose escalation study to determine a safe and effective maximum tolerated dose of HS-130 in combination with viagenpumatucel-L (HS-110) for adult subjects with advanced solid tumors who are refractory to Standard of Care.

Detailed Description

      This is an open-label, non-controlled, first-in-human Phase I study of HS-130 and HS-110 in
      patients with advanced solid tumors refractory to, or ineligible for, Standard of Care.

      Seven dose levels will be explored in escalating doses. For each dose level, patients will
      receive combination HS-130 and HS-110 via intradermal injections once every 14 days. The Dose
      Limiting Toxicity (DLT) window of observation will include the first 28 days of treatment. In
      the absence of progressive disease or unacceptable toxicity, patients will continue to
      receive combination treatment every two weeks until disease progression, death, patient's
      withdrawal of consent, Investigator decision to discontinue treatment, or intolerable
      toxicity, whichever occurs first.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1: HS-130 + HS-110 (viagenpumatucel-L)ExperimentalPatients will receive a combination of intradermal HS-130 and HS-110 once every 14 days. The dose levels will be determined by the starting dose and the escalation steps outlined in the protocol.
  • HS-110 (viagenpumatucel-L)
  • HS-130

Eligibility Criteria

        Inclusion Criteria:

          1. Patients with metastatic or advanced, unresectable solid tumor who have progressed, or
             recurred following standard-of-care (SOC) therapies or are ineligible for safe and
             effective SOC therapies and for whom, in the opinion of the Investigator, experimental
             therapy with HS-130/HS-110 may be beneficial.

          2. Patients should have lesions that are safely accessible for biopsy and be willing to
             provide pre-treatment and on-treatment tissue biopsy. Fine-needle aspiration biopsy is
             not acceptable. Archival tumor tissue will be accepted in lieu of fresh biopsy at
             screening if sample was collected within 6-months from Cycle 1 Day 1, and the local
             pathologist confirms that an adequate amount of tissue/tumor cells exist to allow
             completion of all testing as outlined in the specimen collection manual.

          3. Age ≥ 18 years.

          4. Have an acceptable organ function:

               -  Albumin ≥ 2.5 g/dL.

               -  Total Bilirubin < 3.0 × upper limit of normal (ULN) unless patient has Gilbert's
                  syndrome.

               -  Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3.0 × ULN or ≤ 5 ×
                  ULN in the case of liver metastases.

               -  Calculated or measured creatinine clearance > 35 mL/minute per the
                  Cockcroft-Gault formula.

               -  Absolute neutrophil count ≥ 1,500/mm3.

               -  Hemoglobin ≥ 9 g/dL.

               -  Platelet count ≥ 100,000/mm3.

          5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          6. Life expectancy of at least three months.

          7. Patients, both females and males, of childbearing/reproductive potential must agree to
             use adequate contraception while included in the trial and for six months after the
             last treatment with HS-130 and/or HS-110.

          8. Patients must be willing and have the capacity to sign the informed consent form.

        Exclusion Criteria:

          1. Have clinically significant cardiac disease, including:

               -  Onset of unstable angina within 6 months of signing the Informed Consent Form
                  (ICF).

               -  Acute myocardial infarction within 6 months of the signing the ICF.

               -  Known congestive heart failure (Grade III or IV as classified by the New York
                  Heart Association); and/ or a known decreased cardiac ejection fraction (LVEF) of
                  < 45%.

               -  Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or
                  diastolic blood pressure ≥ 100 mmHg, despite optimal medical management.

          2. Known or clinically suspected leptomeningeal disease. Stable, previously treated
             metastases in the brain or spinal cord, are allowed as long as these are considered
             stable (by CT or MRI), and not requiring systemic corticosteroids.

          3. History of ≥ grade 3 allergic reactions as well as known or suspected allergy or
             intolerance to any agent given in the course of this trial, live cell therapies, or
             live vaccines.

          4. History of suspected cytokine release syndrome (CRS).

          5. Known immunodeficiency disorders (testing not required).

          6. Ongoing or current autoimmune disease. Permanent but stable and manageable immune
             related adverse events (irAE) from prior therapies are permissible, if prednisone
             equivalent corticosteroid use does not exceed 10 mg/day.

          7. Any other condition requiring concurrent systemic immunosuppressive therapy (other
             than allowable exceptions which do not exceed 10mg/day of prednisone/corticosteroid
             use).

          8. Major surgery (requiring general anesthesia or inpatient hospitalization) within four
             weeks before first IMP administration.

          9. Any ongoing anticancer therapy including; small molecules, immunotherapy,
             chemotherapy, monoclonal antibodies or any other experimental drug. Prior therapy must
             be stopped within four weeks before first infusion in the study, or 5 half-lives, or
             twice the duration of the biological effect of the investigational product (whichever
             is shortest). Adjuvant anti-hormonal treatment(s) for previously treated breast cancer
             or prostate cancer are allowed. Bisphosphonates are allowed, Denosumab and other RANK
             ligand inhibitors are prohibited.

         10. Known current malignancy other than inclusion diagnosis. Prior curable cancer with
             complete remission for >2 years is allowed.

         11. Any other ongoing significant, uncontrolled medical condition as per Investigator
             discretion.

         12. Received a live vaccine within 30 days prior to first dose of study drug.

         13. Clinically significant active viral, bacterial or fungal infection requiring:

               1. Intravenous treatment with antimicrobial therapy completed less than two weeks
                  prior to first dose, or

               2. Oral treatment with antimicrobial therapy completed less than one week prior to
                  first dose.

             Prophylactic treatment with antibiotics (e.g. for dental extractions) is allowed.

         14. Known positive serology for human immunodeficiency virus (HIV), hepatitis B, or
             hepatitis C (except in cases of immunity after cured infection). Testing not required.

         15. Substance abuse, medical, psychological or social conditions that may interfere with
             the patient's participation in the trial or evaluation of the trial result in the
             opinion of the Investigator.

         16. Women who are pregnant or breast feeding.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Frequency of TEAEs, SAEs, and DLTs
Time Frame:Up to 18 months
Safety Issue:
Description:Treatment emergent adverse events (TEAEs), serious adverse events (SAEs) and dose-limiting toxicities (DLTs) will be assessed by CTCAE v5.0

Secondary Outcome Measures

Measure:Best Overall Response
Time Frame:Up to 16 months
Safety Issue:
Description:Best Overall Response (BOR) as determined using RECIST v1.1.
Measure:Overall Survival
Time Frame:Up to 18 months
Safety Issue:
Description:Overall Survival (OS) will be calculated as the duration from the date of first dose until the date of death from any cause, or is censored at date last known alive.
Measure:Progression-Free Survival
Time Frame:Up to 18 months
Safety Issue:
Description:Progression-Free Survival (PFS) is defined as the duration from the date of first dose to the date of the first documented tumor progression (per RECIST v1.1) or death due to any cause.
Measure:Immunological effect
Time Frame:Up to 18 months
Safety Issue:
Description:Immunological effect will be assessed by evaluating proportions of natural killer (NK) and T cell subsets for levels of activation, memory and exhaustion using flow cytometry

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Heat Biologics

Trial Keywords

  • Cancer
  • Immunotherapy
  • Vaccine
  • Intradermal
  • gp96
  • OX40
  • Combination Therapy
  • Co-stimulation
  • Heat Biologics

Last Updated