Testing a new treatment for advanced solid tumors

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

This study is testing a new treatment called tolododekin alfa for people with advanced solid tumors that haven't improved with standard therapies to see how safe it is and how well it works.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 97 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ankyra Therapeutics, Inc (Industry-sponsored)
• Drugs / interventions: cemiplimab, prednisone
• Locations: 5 sites (Bethesda, Maryland and 4 other locations)
• Trial ID: NCT06171750 on ClinicalTrials.gov

What this trial studies

This Phase 1 multicenter study evaluates the safety and tolerability of tolododekin alfa (ANK-101) administered via intratumoral injection in patients with advanced solid tumors that have progressed after standard therapies. The study is divided into three parts: the first focuses on superficial lesions, the second on visceral lesions, and the third examines the combination of ANK-101 with cemiplimab for high-risk cutaneous squamous cell carcinoma. Participants will be enrolled in sequential dose-escalation cohorts to determine the recommended dose for further studies. The study aims to assess pharmacokinetics, pharmacodynamics, and preliminary clinical activity of the treatment.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced solid tumors that are accessible for intratumoral injection and have progressed after standard treatment.

Not a fit: Patients with early-stage tumors or those who are candidates for surgical intervention may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that are resistant to standard therapies.

How similar studies have performed: Other studies using intratumoral therapies have shown promise, but this specific approach with tolododekin alfa is novel.

Eligibility criteria

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

Where this trial is running

Bethesda, Maryland and 4 other locations

• National Cancer Institute — Bethesda, Maryland, United States (Recruiting)
• Massachusetts General Hospital — Boston, Massachusetts, United States (Recruiting)
• Providence Cancer Institute — Portland, Oregon, United States (Recruiting)
• Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (Recruiting)
• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Study coordinator: Gail Iodice, BSN, RN

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