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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Advanced Solid Tumor
- Sponsor
- Heat Biologics
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Dose Limiting Toxicity
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
- •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.
- •Age ≥ 18 years.
- •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/mm
- •Hemoglobin ≥ 9 g/dL.
Exclusion Criteria
- •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.
- •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.
- •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.
- •History of suspected cytokine release syndrome (CRS).
- •Known immunodeficiency disorders (testing not required).
- •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.
Outcomes
Primary Outcomes
Dose Limiting Toxicity
Time Frame: 1 month
Number of Patients with Dose Limiting Toxicity (DLT)