ANK-101 for Cancer

(ANCHOR Trial)

Recruiting at 3 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

107 Participants Needed

Trial Summary

What is the purpose of this 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 (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.

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.

What data supports the effectiveness of the treatment ANK-101 for cancer?

Research shows that ANK-101, a form of interleukin-12 (IL-12) anchored to aluminum hydroxide, has shown strong antitumor effects in animal studies. It was effective in shrinking tumors and activating the immune system to fight cancer, with fewer side effects compared to unanchored IL-12. ^{1 2 3 4 5}

What safety data exists for ANK-101 and IL-12 treatments?

ANK-101, a form of IL-12, has shown a good safety profile in animal studies, with subcutaneous administration in monkeys being well tolerated. However, IL-12, when given systemically in humans, has been linked to side effects like fever, flu-like symptoms, fatigue, and liver issues, but local administration methods are being explored to reduce these toxicities. ^{2 4 5 6 7}

What makes the drug ANK-101 unique for cancer treatment?

ANK-101 is unique because it combines interleukin-12 (IL-12), a protein that boosts the immune system, with aluminum hydroxide to create a stable complex that stays in the tumor longer, reducing the need for frequent doses and minimizing side effects compared to traditional IL-12 treatments. ^{2 5 6 8 9}

Research Team

Joseph Elassal, MD, MBA

Principal Investigator

Ankyra Therapeutics, Inc

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

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

2. Germany pubmed.ncbi.nlm.nih.gov

Interleukin-12 as an in situ cancer vaccine component: a review. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Interleukin 12: still a promising candidate for tumor immunotherapy? [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

Addition of interleukin 12 to low dose interleukin 2 treatment improves antitumor efficacy in vivo. [2009]

5. United States pubmed.ncbi.nlm.nih.gov

Intratumoral aluminum hydroxide-anchored IL-12 drives potent antitumor activity by remodeling the tumor microenvironment. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

[Clinical trial of IL-12 for cancer patients]. [2007]

7. England pubmed.ncbi.nlm.nih.gov

New insights into IL-12-mediated tumor suppression. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Antitumor and antimetastatic activity of interleukin 12 against murine tumors. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Application of interleukin 12 to antitumor cytokine and gene therapy. [2019]