Phase I Study of ANK-101 in Advanced Solid Tumors

Solid Tumor Clinical Trial

— ANCHOR  

Official title:

A Phase I Open-Label, Dose Escalation Study of the Safety and Tolerability of ANK-101 in Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06171750
• Other study ID #: ANK-101-001
• Status: Recruiting
• Phase: Phase 1
• Start date: January 19, 2024
• Est. completion date: January 2026

Study information

• Verified date: May 2024
• Source: Ankyra Therapeutics, Inc
• Contact: Gail Iodice, BSN, RN
• Phone: 347-882-1147
• Email: giodice[@]ankyratx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 who have progressed during or after receiving standard of care (SOC) therapy or who will not benefit from such therapy. The study will be conducted in two parts; Part 1 will enroll participants with superficial lesions and Part 2 will enroll participants with visceral lesions.

Description:

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 in participants with superficial or visceral lesions; and 2) determine the recommended dose for expansion (RDE) of ANK-101. For both parts, the study design consists of six sequential dose-escalation cohorts and an expansion cohort at the RDE. Part 1 will enroll participants with advanced solid tumors, with cutaneous, subcutaneous or nodal disease (accessible by clinical palpation or ultrasound guidance). Part 2 will start once the DLT period of dose level 1 in Part 1 is completed and dose level 2 is opened. Part 2 will enroll participants with visceral disease (accessible by interventional radiology or endoscopic techniques). Participants in Part 2 may also have superficial lesions that can be injected if in the Investigator's opinion this is clinically indicated. Ten participants will be dosed in a Part 1 dose expansion cohort at the RDE, and in Part 2, the dose expansion cohort at the RDE will include 10 participants with non-small cell lung cancer (NSCLC).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 92
• Est. completion date: January 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 - For Part 1 only: 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) or; - For Part 2 only: can be accessed by interventional radiologic or endoscopic procedures for injection (e.g., ultrasound or computed tomography [CT] guided). - For Part 2 Dose Expansion Cohort only: Histologically confirmed Stage III or Stage IV NSCLC
• documented disease progression, be refractory to, or intolerant of existing SOC therapy(ies) known to provide clinical benefit (including surgical cure) 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 > 460 msec
• 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 - Note: Part 2 only: Participants with active bleeding diathesis or requirement for therapeutic anticoagulation that cannot be interrupted or altered for procedures
• 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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Cutaneous Tumor
• Malignant Solid Tumor
• Metastatic Solid Tumor
• Neoplasms
• Non Small Cell Lung Cancer
• Skin Neoplasms
• Solid Tumor

Intervention

Drug:
• ANK-101
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.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Providence Cancer Institute	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Ankyra Therapeutics, Inc

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	RDE of ANK-101	Defined based on the rate of DLTs and TEAEs	Approximately 12 months
Secondary	PK: Cmax of IL-12-ABP	PK of IL-12-ABP as assessed by maximum plasma concentration (Cmax)	Up to 2 years
Secondary	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
Secondary	PK: t ½ of IL-12-ABP	PK of IL-12-ABP as assessed by terminal half-life (t ½)	Up to 2 years
Secondary	PK: CL/F of IL-12-ABP	PK of IL-12-ABP as assessed by apparent clearance (CL/F)	Up to 2 years
Secondary	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
Secondary	Levels of ADA in serum	Number and percentage of participants with serum levels of anti drug antibodies (ADA) after treatment	Up to 2 years
Secondary	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
Secondary	DCR by RECIST v1.1	Number of participants with SD, CR and PR.	Up to 2 years
Secondary	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
Secondary	PFS by RECIST v1.1	Time from C1D1 to PD or death from any cause	UP to 2 years