ANK-101 for Cancer
(ANCHOR Trial)
Recruiting in Palo Alto (17 mi)
+3 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Ankyra Therapeutics, Inc
Must be taking: Antiretrovirals
Must not be taking: Immunosuppressants, Steroids
Disqualifiers: Immunodeficiency, Hepatitis, CNS metastases, others
No Placebo Group
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?
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.24567
What makes the drug ANK-101 unique for cancer treatment?
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.
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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
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Trial 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 (Virus Therapy)
Trial OverviewThe 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
3Treatment groups
Experimental Treatment
Group I: tolododekin alfa (ANK-101) IT Injection in Visceral LesionsExperimental Treatment1 Intervention
IT injections of ANK-101 once every 3 weeks into visceral lesions
Group II: tolododekin alfa (ANK-101) IT Injection in Superficial LesionsExperimental Treatment1 Intervention
IT injections of ANK-101 once every 3 weeks into superficial lesions
Group III: tolododekin alfa (ANK-101) IT Injection in Combination with CemiplimabExperimental Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Hillman Cancer CenterPittsburgh, PA
Princess Margaret Cancer CentreToronto, Canada
Massachusetts General HospitalBoston, MA
Providence Cancer InstitutePortland, OR
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Who Is Running the Clinical Trial?
Ankyra Therapeutics, IncLead Sponsor
References
Antitumor effects of interleukin-12 (IL-12): applications for the immunotherapy and gene therapy of cancer. [2018]Interleukin-12 (IL-12) is a pleiotropic cytokine, formerly termed cytotoxic lymphocyte maturation factor (CLMF) or natural killer cell stimulatory factor (NKSF), which is produced primarily by stimulated macrophages. IL-12 is a disulfide-linked heterodimeric cytokine composed of a 35-kDa light chain (p35) and a 40-kDa heavy chain (p40). Unlike most other cytokines, simultaneous transfection of mammalian cells with two different genes is necessary for the production of biologically active IL-12. IL-12 exerts a variety of biological effects on human T and natural killer (NK) cells in vitro, in addition to its ability to promote cytolytic activity, including direct stimulation of the production of IFN-gamma and other cytokines from peripheral blood T and NK cells. The recent finding that IL-12 directs the development of a TH1 type immune response from naive T cells demonstrates the critical role of IL-12 in regulating the immune response. The characteristics of IL-12 function described above strongly suggest its potential usefulness in cancer therapy. Indeed, our studies demonstrate that IL-12 exerts potent antitumor effects following systemic or local administration. We have shown that IL-12 delivered by retroviral vectors allows high-level expression and effective eradication of established tumor in multiple murine tumor models including MCA207 sarcoma. Successful therapy is associated with acquisition of a state of long-term, specific and protective immunity to subsequent challenge with tumor. We have recently received approval from the Recombinant DNA Advisory Committee to proceed with IL-12 gene therapy in humans.
Interleukin-12 as an in situ cancer vaccine component: a review. [2022]Interleukin-12 (IL-12) is a type I cytokine involved in both innate and adaptive immunity that stimulates T and natural killer cell activity and induces interferon gamma production. IL-12 has been identified as a potential immunotherapeutic component for combinatorial cancer treatments. While IL-12 has successfully been used to treat a variety of cancers in mice, it was associated with toxicity when administered systemically in cancer patients. In this review, we discuss the research findings and progress of IL-12 used in combination with other cancer treatment modalities. We describe different methods of IL-12 delivery, both systemic and local, and ultimately highlight the potential of an in situ vaccination approach for minimizing toxicities and providing antitumor efficacy. This review offers a basis for pursuing an in situ vaccine approach that may eventually allow IL-12 to be more readily integrated as an immunotherapy into the clinical treatment of cancers.
Interleukin 12: still a promising candidate for tumor immunotherapy? [2022]Interleukin 12 (IL-12) seemed to represent the ideal candidate for tumor immunotherapy, due to its ability to activate both innate (NK cells) and adaptive (cytotoxic T lymphocytes) immunities. However, despite encouraging results in animal models, very modest antitumor effects of IL-12 in early clinical trials, often accompanied by unacceptable levels of adverse events, markedly dampened hopes of the successful use of this cytokine in cancer patients. Recently, several clinical studies have been initiated in which IL-12 is applied as an adjuvant in cancer vaccines, in gene therapy including locoregional injections of IL-12 plasmid and in the form of tumor-targeting immunocytokines (IL-12 fused to monoclonal antibodies). The near future will show whether this renewed interest in the use of IL-12 in oncology will result in meaningful therapeutic effects in a select group of cancer patients.
Addition of interleukin 12 to low dose interleukin 2 treatment improves antitumor efficacy in vivo. [2009]Interleukin 12 (IL-12) enhances lysis mediated by NK- and lymphokine activated killer (LAK) cells. It also causes proliferation of IL-2 stimulated T and NK cells in vitro. For these IL-2 complementing properties murine pulmonary metastases of a coloncarcinoma line were treated with IL-12 and IL-2 or with the individual agents. Results were compared to sham treated controls. IL-2 alone mediated significant tumor reduction but provoked pulmonary edema and concomittand toxicity, graded in three steps. IL-12 combined with an IL-2 dose reduced by 81% still resulted in significant antitumoral activity. Toxicity, however, was not discernable from sham treated controls. IL-12 thus appears as an attractive cytokine for combination with IL-2 in antitumor therapy. Particularly treatment of tumors, like gastrointestinal tract cancers, so far mainly resistant to cell mediated antitumor therapy, might profit from this approach.
Intratumoral aluminum hydroxide-anchored IL-12 drives potent antitumor activity by remodeling the tumor microenvironment. [2023]IL-12 is a potent cytokine that can promote innate and adaptive anticancer immunity, but its clinical development has been limited by toxicity when delivered systemically. Intratumoral (i.t.) administration can expand the therapeutic window of IL-12 and other cytokines but is in turn limited by rapid drug clearance from the tumor, which reduces efficacy, necessitates frequent administration, and increases systemic accumulation. To address these limitations, we developed an anchored IL-12 designated ANK-101, composed of an engineered IL-12 variant that forms a stable complex with the FDA-approved vaccine adjuvant aluminum hydroxide (Alhydrogel). Following i.t. administration of murine ANK-101 (mANK-101) in early intervention syngeneic mouse tumors, the complex formed a depot that was locally retained for weeks as measured by IVIS or SPECT/CT imaging, while unanchored protein injected i.t. was cleared within hours. One or 2 i.t. injections of mANK-101 induced single-agent antitumor activity across a diverse range of syngeneic tumors, including models resistant to checkpoint blockade at doses where unanchored IL-12 had no efficacy. Local treatment with mANK-101 further induced regressions of noninjected lesions, especially when combined with systemic checkpoint blockade. Antitumor activity was associated with remodeling of the tumor microenvironment, including prolonged IFN-γ and chemokine expression, recruitment and activation of T and NK cells, M1 myeloid cell skewing, and increased antigen processing and presentation. Subcutaneous administration of ANK-101 in cynomolgus macaques was well tolerated. Together, these data demonstrate that ANK-101 has an enhanced efficacy and safety profile and warrants future clinical development.
[Clinical trial of IL-12 for cancer patients]. [2007]Interleukin-12 (IL-12) is a cytokine that stimulates T cells and NK cells. It induces interferon-gamma and plays a unique role in promoting type 1 T helper cell responses. In various animal models, IL-12 has shown a therapeutic effect controlling growth of primary and metastatic tumors at nontoxic doses. On the basis of these findings, IL-12 is now under clinical trial. Fever, flu-like, general fatigue, arthralgia, myalgia, leukopenia, liver dysfunction and so on are the reported toxicities of IL-12. A dramatic decrease of IL-12 AUC after consecutive dosing of IL-12, production of IL-10 and temporal elevation of NK and LAK activities after IL-12 administration have also been observed. Several patients achieve PRs after the administration, but dramatic clinical responses have never been reported. Intensive research on the mechanisms of antitumor response of IL-12 in cancer patients should be very important to the successful development of IL-12 as an anti-cancer agent.
New insights into IL-12-mediated tumor suppression. [2022]During the past two decades, interleukin-12 (IL-12) has emerged as one of the most potent cytokines in mediating antitumor activity in a variety of preclinical models. Through pleiotropic effects on different immune cells that form the tumor microenvironment, IL-12 establishes a link between innate and adaptive immunity that involves different immune effector cells and cytokines depending on the type of tumor or the affected tissue. The robust antitumor response exerted by IL-12, however, has not yet been successfully translated into the clinics. The majority of clinical trials involving treatment with IL-12 failed to show sustained antitumor responses and were associated to toxic side effects. Here we discuss the therapeutic effects of IL-12 from preclinical to clinical studies, and will highlight promising strategies to take advantage of the antitumor activity of IL-12 while limiting adverse effects.
Antitumor and antimetastatic activity of interleukin 12 against murine tumors. [2022]It has recently been demonstrated that in vivo administration of murine interleukin 12 (IL-12) to mice results in augmentation of cytotoxic natural killer (NK)/lymphocyte-activated killer cell activity, enhancement of cytolytic T cell generation, and induction of interferon gamma secretion. In this study, the in vivo activity of murine IL-12 against a number of murine tumors has been evaluated. Experimental pulmonary metastases or subcutaneous growth of the B16F10 melanoma were markedly reduced in mice treated intraperitoneally with IL-12, resulting in an increase in survival time. The therapeutic effectiveness of IL-12 was dose dependent and treatment of subcutaneous tumors could be initiated up to 14 d after injection of tumor cells. Likewise, established experimental hepatic metastases and established subcutaneous M5076 reticulum cell sarcoma and Renca renal cell adenocarcinoma tumors were effectively treated by IL-12 at doses which resulted in no gross toxicity. Local peritumoral injection of IL-12 into established subcutaneous Renca tumors resulted in regression and complete disappearance of these tumors. IL-12 was as effective in NK cell-deficient beige mice or in mice depleted of NK cell activity by treatment with antiasialo GM1, suggesting that NK cells are not the primary cell type mediating the antitumor effects of this cytokine. However, the efficacy of IL-12 was greatly reduced in nude mice suggesting the involvement of T cells. Furthermore, depletion of CD8+ but not CD4+ T cells significantly reduced the efficacy of IL-12. These results demonstrate that IL-12 has potent in vivo antitumor and antimetastatic effects against murine tumors and demonstrate as well the critical role of CD8+ T cells in mediating the antitumor effects against subcutaneous tumors.
Application of interleukin 12 to antitumor cytokine and gene therapy. [2019]In vivo administration of interleukin 12 (IL-12) at 2000 U/mouse induced IL-12-activated killer (IL-12AK) cells in parallel with an elevation in serum interferon-gamma (IFN-gamma) activity. Although NK1.1+CD3- natural killer cells are the major precursor of IL-12AK cells, asialoGM1+CD8+ T-cells were also demonstrated to be novel precursors. Such anomalous killer cells may play an important role in the early stages of the host defense mechanisms against tumors. It was also shown that IL-12 is effective in inducing tumor-specific cytotoxic T-lymphocytes. Consistent with these data, IL-12 had marked activity against various kinds of established tumors when given systemically. Mice cured of tumors by IL-12 treatment acquired tumor-specific T-cell immunity. Moreover, we initially demonstrated that IL-12 was effective in preventing and inhibiting the growth of primary tumors induced by the chemical carcinogen methylnitrosourea using c-Ha-ras transgeneic mice. Finally, we investigated the application of IL-12 to antitumor gene therapy. Transfer of the IL-12 gene into A20 B-lymphoma cells resulted in the continuous production of IL-12 and caused abrogation of in vivo tumorigenicity. Tumor cells transfected with the IL-12 gene are potentially a good tool as a tumor vaccine, as they effectively induced IL-12AK cells, IFN-gamma production, and tumor-specific protective immunity. Although B16-BL-6 melanoma cells, which are a highly metastatic subclone of B16 melanoma cells, showed resistance to IL-12 gene therapy, combination therapy with the B7-1 gene and systemic IL-12 administration almost completely inhibited tumor metastasis. Similar results were obtained using B16-BL-6 melanoma cells transfected with both B7-1 and IL-12 genes. These results suggest that IL-12 is a promising cytokine for antitumor cytokine and gene therapy.