Phase I Study of ANK-101 in Advanced Tumors

Study Overview
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Brief Summary
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This is a Phase 1, multicenter, open-label dose escalation study to determine the safety and tolerability of intratumoral (IT) injection of ANK-101 in participants with advanced solid tumors.

Detailed Description
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This Phase 1 first-in-human (FIH) study will: 1) evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic effects and preliminary clinical activity of ANK-101 administered as an intratumoral (IT) injection; and 2) determine the recommended dose for expansion (RDE) of ANK-101. The study design consists of six sequential dose-escalation cohorts and an expansion cohort at the RDE. Eligible participants with accessible cutaneous, subcutaneous, soft tissue or nodal malignancies who have progressed during or after receiving standard of care (SOC) therapy or who would not benefit from such therapy will be enrolled.

Official Title
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A Phase I Open-Label, Dose Escalation Study of the Safety and Tolerability of ANK-101 in Advanced Cutaneous, Subcutaneous, Soft Tissue or Nodal Tumors

Conditions
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Advanced Solid Tumor, Cutaneous Tumor, Subcutaneous Tumor, Malignant Solid Tumor, Solid Tumor, Metastatic Solid Tumor, Metastasis to Soft Tissue

Intervention / Treatment
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* Drug: ANK-101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age on day of signing informed consent histologically or cytologically confirmed diagnosis of cutaneous, subcutaneous, soft tissue, or nodal advanced solid tumor malignancy; metastatic disease eligible measurable disease per RECIST v1.1 - Note: Must have at least 1 tumor lesion with longest dimension of ≥ 10 mm (≥ 15 mm for the short axis for malignant lymph node lesions) that can be easily palpated or detected by ultrasound to facilitate IT injection of ANK-101 (i.e., tumor in skin, muscle, subcutaneous tissue, or accessible lymph node). documented disease progression, be refractory to, or intolerant of existing SOC therapy(ies) known to provide clinical benefit or not be eligible for SOC therapy(ies) ECOG performance status 0-1 life expectancy > 12 weeks adequate bone marrow, hepatic and renal function baseline electrocardiogram (EKG) without evidence of acute ischemia or prolonged QTc interval > 440 msec in men and > 460 msec in women Human immunodeficiency virus (HIV) infected participants must be on anti-retroviral therapy (ART) and have well-controlled HIV infection/disease last dose of previous anticancer therapy (including investigational agents) ≥ 28 days, radiotherapy ≥ 14 days (targeted palliative radiotherapy is allowed for lesions not planned for injections), or surgical intervention ≥ 21 days prior to the start of treatment resolution of all prior anticancer therapy toxicities (except for alopecia or vitiligo) to ≤ Grade 1 (as per NCI CTCAE Version 5.0) willing to provide pre- and post-treatment tumor biopsy samples if medically feasible participant is capable of understanding and complying with protocol requirements Exclusion Criteria: injectable tumors impinging upon major airways or blood vessels prior treatment with recombinant interleukin-12 (IL-12) have received systemic therapy with immunosuppressive agents ≤ 28 days before the start of treatment have received live vaccines within 28 days prior to the start of ANK-101 treatment have primary or acquired immunodeficient states (e.g., leukemia, lymphoma) a woman of childbearing potential (WOCBP) who has a positive serum pregnancy test (within 72 hours) prior to the start of treatment or female participant who is breastfeeding prior organ transplantation known history of hepatitis B virus, known active hepatitis C virus, or a positive serological test at screening within 28 days prior to the start of treatment HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease active autoimmune disease or medical conditions requiring chronic steroid (i.e., ≥ 20 mg/day prednisone or equivalent) or other immunosuppressive therapy within 28 days prior to the start of treatment known active central nervous system (CNS) metastases congestive heart failure (> New York Heart Association Class II), active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest), or clinically significant cardiac arrhythmias uncontrolled bleeding disorders within 4 weeks prior to the start of treatment or known bleeding diathesis history of hypersensitivity to compounds of similar biological composition to IL-12, aluminum hydroxide, or drugs formulated with polysorbate-20 other systemic conditions or organ abnormalities that, in the opinion of the Investigator, may interfere with the conduct and/or interpretation of the current study any acute or chronic psychiatric problems or substance abuse disorder that, in the opinion of the Investigator, make the participant unsuitable for participation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ANK-101 IT Injection<br>IT injections of ANK-101 once every 3 weeks | Drug: ANK-101<br>* IT administration of ANK-101 once every 3 weeks for up to 12 weeks (4 doses); if there is no disease progression, decrease in clinical performance status or unacceptable toxicity, participants may receive 4 additional doses of ANK-101.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and characteristics of DLTs and TEAEs | Number and percentage of participants reporting each DLT or TEAE. | From Day 1 to 90 days after last injection of ANK-101 | 
| RDE of ANK-101 | Defined based on the rate of DLTs and TEAEs | Approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK: Cmax of IL-12-ABP | PK of IL-12-ABP as assessed by maximum plasma concentration (Cmax) | Up to 2 years | 
| PK: AUC of IL-12-ABP | PK of IL-12-ABP as assessed by area under the time-concentration curve (AUC) | Up to 2 years | 
| PK: t ½ of IL-12-ABP | PK of IL-12-ABP as assessed by terminal half-life (t ½) | Up to 2 years | 
| PK: CL/F of IL-12-ABP | PK of IL-12-ABP as assessed by apparent clearance (CL/F) | Up to 2 years | 
| PK: Vss/F of IL-12-ABP | PK of IL-12-ABP as assessed by apparent volume of distribution at steady state (Vss/F) | Up to 2 years | 
| Levels of ADA in serum | Number and percentage of participants with serum levels of anti drug antibodies (ADA) after treatment | Up to 2 years | 
| ORR by RECIST v1.1 | Number of participants with a best overall RECIST response (BOR) of CR or PR based on RECIST v1.1 | Up to 2 years | 
| DCR by RECIST v1.1 | Number of participants with SD, CR and PR. | Up to 2 years | 
| DOR by RECIST v1.1 | Time from when the criteria for RECIST v1.1 CR or PR (whichever is recorded first) was first met until the date when PD is documented | Up to 2 years | 
| PFS by RECIST v1.1 | Time from C1D1 to PD or death from any cause | UP to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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intratumoral, intratumoral injection, solid tumors, superficial tumors, nodal tumors, subcutaneous tumors