Phase I Study of Tolododekin Alfa (ANK-101) in Advanced Solid Tumors

NCT06171750 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ANK-101-001
• Study Type: interventional
• Target: 97
• Locations: 2 countries
• Sites: 5

Brief Summary

This is a Phase 1, multicenter, open-label dose escalation study to determine the safety and tolerability of intratumoral (IT) injection of tolododekin alfa (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 three parts; in Part 1, participants with superficial lesions will receive ANK-101 as a single agent; in Part 2, participants with visceral lesions will receive ANK-101 as a single agent; and in Part 3, participants with cutaneous squamous cell carcinoma (CSCC) will receive ANK-101 in combination with cemiplimab.

Conditions

Advanced Solid Tumor; Cutaneous Tumor; Subcutaneous Tumor; Malignant Solid Tumor; Solid Tumor; Metastatic Solid Tumor; Metastasis to Soft Tissue; Non Small Cell Lung Cancer; Cutaneous Squamous Cell Carcinoma

Keywords

intratumoral; intratumoral injection; solid tumors; superficial tumors; nodal tumors; subcutaneous tumors; visceral tumors

Outcome Measures

Primary Outcomes (3)

• Incidence and characteristics of DLTs (Parts 1 and 2 only) 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

• Incidence and characteristics of TEAEs of ANK-101 in combination with Cemiplimab according to NCI CTCAE v5.0 (Part 3 only)

  Number and percentage of participants reporting each TEAE.

  From Day 1 to 90 days after last injection of ANK-101 in combination with Cemiplimab.

Secondary Outcomes (10)

• PK: Cmax of IL-12-ABP

  Up to 2 years

• PK: AUC of IL-12-ABP

  Up to 2 years

• PK: t ½ of IL-12-ABP

  Up to 2 years

• PK: CL/F of IL-12-ABP

  Up to 2 years

• PK: Vss/F of IL-12-ABP

  Up to 2 years

Study Arms (3)

tolododekin alfa (ANK-101) IT Injection in Superficial Lesions

EXPERIMENTAL

IT injections of ANK-101 once every 3 weeks into superficial lesions

Drug: tolododekin alfa

tolododekin alfa (ANK-101) IT Injection in Visceral Lesions

EXPERIMENTAL

IT injections of ANK-101 once every 3 weeks into visceral lesions and every 6 weeks in the expansion

Drug: tolododekin alfa

tolododekin alfa (ANK-101) IT Injection in Combination with Cemiplimab

EXPERIMENTAL

IT injections of ANK-101 once every 3 weeks in combination with Cemiplimab into patients with high-risk locally advanced or metastatic CSCC that have superficial lesions

Drug: tolododekin alfa; Drug: Cemiplimab

Interventions

tolododekin alfa DRUG

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.

Also known as: ANK-101

tolododekin alfa (ANK-101) IT Injection in Combination with Cemiplimab; tolododekin alfa (ANK-101) IT Injection in Superficial Lesions; tolododekin alfa (ANK-101) IT Injection in Visceral Lesions

Cemiplimab DRUG

Participants will receive four cycles of ANK-101 in combination with Cemiplimab. If there is no significant clinical deterioration as determined by the Investigator or unacceptable toxicity at Week 12, participants may receive an additional four cycles of the combination treatment. After stopping ANK-101 treatment, participants may stay on Cemiplimab monotherapy for an additional 24 weeks.

Also known as: Libtayo

tolododekin alfa (ANK-101) IT Injection in Combination with Cemiplimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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
• Part 3 CSCC Combination Cohort: Histologically confirmed high-risk locally advanced or metastatic CSCC not amenable to surgical management as determined by a multidisciplinary tumor board.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ankyra Therapeutics, Inc: lead

Study Sites (5)

National Cancer Institute

Bethesda, Maryland, 20892, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Providence Cancer Institute

Portland, Oregon, 97213, United States

RECRUITING

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Related Publications (1)

• Park JC, Curti B, Butler M, Wehrenberg-Klee E, Elassal J, Tighe R, Battula S, Iodice G, Kaufman HL, Kirkwood JM. Interleukin-12 anchored drug conjugate (tolododekin alfa) in patients with advanced solid tumors: first-in-human Phase 1 trial. Nat Commun. 2025 Sep 29;16(1):8567. doi: 10.1038/s41467-025-63579-9.

  PMID: 41022754 DERIVED

MeSH Terms

Conditions

Skin Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung

Interventions

cemiplimab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Joseph Elassal, MD, MBA

  Ankyra Therapeutics, Inc

  STUDY DIRECTOR

Central Study Contacts

Gail Iodice, BSN, RN

CONTACT

347-882-1147; giodice@ankyratx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2023
• First Posted: December 15, 2023
• Study Start: January 19, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Locations

US (4); CA (1)