ANK-101 for Cancer

(ANCHOR Trial)

Recruiting at 4 trial locations

Overseen By Gail Iodice, BSN, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ankyra Therapeutics, Inc

Must be taking: Antiretrovirals

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Hepatitis, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

97 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ANK-101 (Anchored Interleukin-12, a type of immunotherapy) for individuals with advanced solid tumors, including those unresponsive to standard treatments. The study examines the safety and tolerability of the treatment when injected directly into tumors. It consists of three parts: one for tumors just under the skin, another for deeper tumors, and a third combining ANK-101 with another drug for skin cancer. Individuals with advanced tumors that have continued to grow despite other treatments might be suitable candidates. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you must not have received systemic therapy with immunosuppressive agents or live vaccines within 28 days before starting the trial treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that tolododekin alfa (ANK-101) has been tested for safety in people with advanced solid tumors. Early results suggest it is generally safe. These studies have focused on assessing tolerability.

For the combination of ANK-101 with cemiplimab, early data indicates it is safe and has some effects on the body. Researchers are evaluating both its safety and the body's response.

As a Phase 1 trial, the primary goal is to ensure safety for participants. If it were not safe, it would not be in this phase of testing. Phase 1 focuses on confirming the treatment's safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about ANK-101 because it offers a novel approach to treating cancer by directly targeting lesions with intratumoral (IT) injections. Unlike traditional chemotherapy or radiation, which can affect the whole body, ANK-101 delivers the treatment directly into the tumor, potentially reducing side effects. The treatment also explores the combination with Cemiplimab, a PD-1 inhibitor, which could enhance the immune system's ability to fight cancer, particularly in patients with advanced cases of cutaneous squamous cell carcinoma (CSCC). This targeted delivery and combination approach could offer a more effective and safer treatment option for patients with high-risk cancers.

What evidence suggests that ANK-101 might be an effective treatment for advanced solid tumors?

Research has shown that tolododekin alfa (ANK-101) uses interleukin-12 to boost the immune system and directly target cancer cells. Early results suggest this helps keep the drug focused on tumors, potentially increasing its effectiveness. In this trial, participants will receive ANK-101 as an IT injection into either visceral or superficial lesions. In patients with advanced solid tumors, ANK-101 increased CD8+ T cells, which are crucial for attacking cancer cells. Another arm of this trial will study ANK-101 in combination with cemiplimab, a treatment for some skin cancers, which may further enhance the immune system's ability to fight tumors. While more research is needed, these early signs offer hope for its potential in treating various cancers. ^{1 5 6 7 8}

Who Is on the Research Team?

Joseph Elassal, MD, MBA

Principal Investigator

Ankyra Therapeutics, Inc

Are You a Good Fit for This Trial?

This trial is for individuals with advanced solid tumors, including skin cancer and metastatic tumors. Participants must be able to receive injections directly into their tumor.

Inclusion Criteria

It's been over a month since my last cancer treatment or surgery.

My cancer originates from skin, under the skin, soft tissue, or lymph nodes and has spread.

My condition worsened despite standard treatments, or I can't tolerate them.

Exclusion Criteria

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

Positive serum pregnancy test (within 72 hours) prior to the start of treatment or female participant who is breastfeeding

Any acute or chronic psychiatric problems or substance abuse disorder that make the participant unsuitable for participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants with superficial lesions receive ANK-101 as a single agent in a dose-escalation study

Approximately 12 months

Injections every 3 weeks

Treatment Part 2

Participants with visceral lesions receive ANK-101 as a single agent in a dose-escalation study

Approximately 12 months

Injections every 3 weeks

Treatment Part 3

Participants with high-risk locally advanced or metastatic CSCC receive ANK-101 in combination with cemiplimab

Approximately 12 months

Injections every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after last injection

What Are the Treatments Tested in This Trial?

Interventions

• ANK-101

Trial Overview The study is testing ANK-101, a new treatment given as an injection directly into the tumor (intratumoral). It's in Phase 1 to see how safe it is and what dose might be best.

How Is the Trial Designed?

Group I: tolododekin alfa (ANK-101) IT Injection in Visceral Lesions Experimental Treatment 1 Intervention

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

Group II: tolododekin alfa (ANK-101) IT Injection in Superficial Lesions Experimental Treatment 1 Intervention

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

Group III: tolododekin alfa (ANK-101) IT Injection in Combination with Cemiplimab Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Ankyra Therapeutics, Inc

Lead Sponsor

Trials

1

Recruited

110+

Published Research Related to This Trial

ANK-101, an engineered IL-12 variant combined with aluminum hydroxide, shows enhanced retention in tumors and prolonged therapeutic effects compared to unanchored IL-12, which clears quickly after intratumoral administration.

In mouse models, ANK-101 not only demonstrated significant antitumor activity with fewer injections but also improved the tumor microenvironment, leading to immune cell activation and potential benefits when combined with systemic therapies, while being well tolerated in cynomolgus macaques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intratumoral aluminum hydroxide-anchored IL-12 drives potent antitumor activity by remodeling the tumor microenvironment. Battula, S., Papastoitsis, G., Kaufman, HL., et al.[2023]

Interleukin-12 (IL-12) has shown promise in animal studies for controlling tumor growth at nontoxic doses, and it is currently being tested in clinical trials for its potential as an anti-cancer treatment.

While some patients have experienced partial responses to IL-12, the treatment is associated with side effects like flu-like symptoms and liver dysfunction, highlighting the need for further research on its mechanisms and safety in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical trial of IL-12 for cancer patients]. Ohe, Y., Kasai, T., Heike, Y., et al.[2007]

IL-12 enhances the effectiveness of IL-2 in reducing tumors, specifically in murine models of colon carcinoma, while significantly lowering the toxicity associated with IL-2 treatment.

Combining IL-12 with a reduced dose of IL-2 led to substantial tumor reduction without the harmful side effects seen with IL-2 alone, suggesting that IL-12 could be a promising addition to cancer therapies, especially for hard-to-treat gastrointestinal cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of interleukin 12 to low dose interleukin 2 treatment improves antitumor efficacy in vivo. Leder, GH., Oppenheim, M., Rosenstein, M., et al.[2009]

Interleukin-12 (IL-12) has shown strong antitumor activity in various preclinical models by enhancing immune responses, but this success has not been replicated in clinical settings due to limited sustained responses and significant side effects.

The review discusses potential strategies to harness IL-12's antitumor effects while minimizing its toxicity, indicating that further research is needed to improve its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New insights into IL-12-mediated tumor suppression. Tugues, S., Burkhard, SH., Ohs, I., et al.[2022]

Interleukin-12 (IL-12) shows promise as an immunotherapy for cancer by enhancing T and natural killer cell activity, but systemic administration has led to toxicity in cancer patients.

The review suggests that using an in situ vaccination approach for IL-12 delivery could reduce toxicities while maintaining its antitumor efficacy, making it a more viable option for clinical cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin-12 as an in situ cancer vaccine component: a review. Cheng, EM., Tsarovsky, NW., Sondel, PM., et al.[2022]

In vivo administration of murine interleukin 12 (IL-12) significantly reduced tumor growth and increased survival in mice with various types of tumors, including melanoma and renal cell adenocarcinoma, without causing gross toxicity.

The antitumor effects of IL-12 are primarily mediated by CD8+ T cells, as its efficacy was diminished in mice lacking these cells, while NK cells were not the main drivers of the response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor and antimetastatic activity of interleukin 12 against murine tumors. Brunda, MJ., Luistro, L., Warrier, RR., et al.[2022]

Interleukin 12 (IL-12) has shown potential in activating immune responses against tumors, but early clinical trials revealed only modest antitumor effects and significant adverse events, limiting its effectiveness in cancer treatment.

New approaches are being explored, such as using IL-12 as an adjuvant in cancer vaccines and in gene therapy, which may enhance its therapeutic impact in specific cancer patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interleukin 12: still a promising candidate for tumor immunotherapy? Lasek, W., Zagożdżon, R., Jakobisiak, M.[2022]

In vivo administration of interleukin 12 (IL-12) significantly enhances the activation of killer cells and increases serum interferon-gamma levels, demonstrating its potential to boost the immune response against tumors.

IL-12 not only shows effectiveness in treating established tumors but also in preventing tumor growth, particularly when combined with gene therapy strategies, suggesting it could be a powerful tool in cancer treatment and immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of interleukin 12 to antitumor cytokine and gene therapy. Nishimura, T., Watanabe, K., Yahata, T., et al.[2019]

Interleukin-12 (IL-12) is a powerful cytokine that enhances the immune response by stimulating T and natural killer (NK) cells, promoting the production of important cytokines like IFN-gamma, and directing the development of a TH1 immune response.

IL-12 has shown strong antitumor effects in various murine models, and its delivery via retroviral vectors has led to effective tumor eradication and long-term immunity, paving the way for upcoming human gene therapy trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effects of interleukin-12 (IL-12): applications for the immunotherapy and gene therapy of cancer. Tahara, H., Lotze, MT.[2018]

Citations

1. businesswire.com businesswire.com/news/home/20250428550798/en/Ankyra-Therapeutics-Announces-Phase-1-Clinical-Data-at-the-2025-AACR-Annual-Meeting-and-the-first-patient-has-been-dosed-with-tolododekin-alfa-and-cemiplimab

Ankyra Therapeutics Announces Phase 1 Clinical Data at ... Tolododekin alfa (ANK-101) is an anchored drug conjugate composed of interleukin-12 (IL-12) linked to aluminum hydroxide. ANK-101 enables local ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06171750

NCT06171750 | Phase I Study of Tolododekin Alfa (ANK- ... This is a Phase 1, multicenter, open-label dose escalation study to determine the safety and tolerability of intratumoral (IT) injection of tolododekin alfa ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12480005/

Interleukin-12 anchored drug conjugate (tolododekin alfa) ... PK/Pharmacodynamic measurements demonstrate retention of drug in the tumour. Biological activity demonstrates increased CD8+ T cells, Programmed ...

4. researchgate.net researchgate.net/publication/389698153_Interleukin-12_anchored_drug_conjugate_tolododekin_alfa_in_patients_with_advanced_solid_tumors_Results_of_a_first-in-human_Phase_1_trial

Interleukin-12 anchored drug conjugate (tolododekin alfa) ... PK/PD measurements demonstrated retention of drug in the tumor at all dose levels. Biologic activity was demonstrated by increased CD8+ T cells, ...

5. delta.larvol.com delta.larvol.com/Products/?ProductId=caa20707-4c12-48e1-80c5-68446ef676ed

tolododekin alfa (ANK-101) / Ankyra Therap P1 data • Trial status • Bladder Cancer • Breast Cancer • Head and Neck Cancer • Melanoma • Skin Cancer • Squamous Cell Carcinoma • Squamous Cell Skin Cancer.

6. ankyratx.com ankyratx.com/press-releases/ankyra-therapeutics-announces-phase-1-clinical-data-at-the-2025-aacr-annual-meeting-and-the-first-patient-has-been-dosed-with-tolododekin-alfa-and-cemiplimab/

Ankyra Therapeutics Announces Phase 1 Clinical Data at ... ... data highlighting the safety and biologic activity of their lead asset, tolododekin alfa (ANK-101), an anchored interleukin-12 (IL-12) drug ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41022754/

Interleukin-12 anchored drug conjugate (tolododekin alfa) ... Safety and biological activity were evaluated in a Phase 1 clinical trial in patients with accessible advanced solid tumours in Part 1 of a 3- ...

8. withpower.com withpower.com/trial/phase-1-solid-tumors-advanced-solid-tumors-11-2023-60215

ANK-101 for Cancer (ANCHOR Trial) This is a Phase 1, multicenter, open-label dose escalation study to determine the safety and tolerability of intratumoral (IT) injection of tolododekin alfa ...