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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor; Non Small Cell Lung Cancer; Advanced Solid Tumor; Metastatic Solid Tumor; Malignant Solid Tumor; Cutaneous Squamous Cell Carcinoma; Cutaneous Tumor; Subcutaneous Tumor; Metastasis to Soft Tissue
• Intervention / Treatment: Drug: Cemiplimab; Drug: tolododekin alfa

Detailed Description

This Phase 1 first-in-human (FIH) study will: 1) evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic effects and preliminary clinical activity of tolododekin alfa (ANK-101) administered as an intratumoral (IT) injection in participants with superficial or visceral lesions; 2) determine the recommended dose for expansion (RDE) of ANK-101; and 3) to determine the safety and tolerability of ANK-101 in combination with cemiplimab.

For parts 1 and 2, the study design consists of six sequential dose-escalation cohorts. 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 with non-small cell lung cancer (NSCLC) will be dosed in a Part 2 dose expansion cohort at the RDE.

Part 3 will start once dose escalation for Part 1 is complete and the RDE is identified. Part 3 will consist of ANK-101 in combination with cemiplimab in 15 participants with high-risk locally advanced or metastatic CSCC that have superficial lesions for injection. Participants will be treated with ANK-101 given as IT injections once every three weeks at the RDE in combination with cemiplimab.

Enrollment in Part 3 will include a safety run-in of 5 participants. Following the first dose of the 5th participant, enrollment will pause for 21 days before opening enrollment to the remaining 10 participants or stopping further enrollment.

• Study Type: Interventional
• Enrollment (Estimated): 97
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gail Iodice, BSN, RN; Phone Number: 347-882-1147; Email: giodice@ankyratx.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre
      • Contact: Marcus Butler, MD; Phone Number: (416) 946-4575; Email: Marcus.Butler@uhn.ca
• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Cancer Institute
      • Contact: Hoyoung Maeng, MD; Phone Number: 240-781-3253; Email: hoyoung.maeng@nih.gov
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Jong Park, MD; Phone Number: 617-724-4000; Email: JPARK73@MGH.HARVARD.EDU
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Cancer Institute
      • Contact: Brendan Curti, MD; Email: CanRsrchStudies@providence.org
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • Hillman Cancer Center
      • Contact: Danielle Bednarz, BS, RN; Phone Number: 412-623-1191; Email: bednarzdl@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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
• 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

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
• Part 3 only: prior Grade 3 or greater immune-mediated adverse events (imAEs) following treatment with an agent that blocks the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway.
• Part 3 only: hypersensitivity to cemiplimab or any of its excipients or contraindications to cemiplimab per approved local labeling

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tolododekin alfa (ANK-101) IT Injection in Superficial Lesions; IT injections of ANK-101 once every 3 weeks into superficial lesions	Drug: tolododekin alfa; 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.; Other Names: ANK-101
Experimental: tolododekin alfa (ANK-101) IT Injection in Combination with Cemiplimab; 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: Cemiplimab; 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.; Other Names: Libtayo; Drug: tolododekin alfa; 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.; Other Names: ANK-101
Experimental: tolododekin alfa (ANK-101) IT Injection in Visceral Lesions; IT injections of ANK-101 once every 3 weeks into visceral lesions and every 6 weeks in the expansion	Drug: tolododekin alfa; 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.; Other Names: ANK-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RDE of ANK-101	Defined based on the rate of DLTs and TEAEs	Approximately 12 months
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
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 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

Collaborators and Investigators

• Sponsor: Ankyra Therapeutics, Inc
• Investigators: Study Director: Joseph Elassal, MD, MBA, Ankyra Therapeutics, Inc

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 29, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): March 6, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: solid tumors; intratumoral injection; intratumoral; superficial tumors; nodal tumors; subcutaneous tumors; visceral tumors
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Skin Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Skin Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; cemiplimab
• Other Study ID Numbers: ANK-101-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No