This study is currently recruiting participants.
Cancer is the second leading cause of death worldwide. Despite recent advances in cancer immunotherapy, better treatments are still needed. ANK-101 was designed with an intention to make the immunotherapy agent to stay longer inside the tumor when directly injected into tumor.
To test a study drug (ANK-101) in people with advanced cancer.
Part 1: People aged 18 years and older with advanced tumors that can be seen or felt through the skin.
Part 3: People with advanced skin cancer with squamous cell type (CSCC) who progressed after cemiplimab
Participants will be screened. They will have a physical exam. They will have blood tests and tests of their heart function. They will have imaging scans of their chest, abdomen, pelvis, and brain. Their ability to perform everyday tasks will be assessed. They will complete questionnaires about their quality of life. Photos may be taken of their tumors. They may have biopsies: Tissue samples may be cut from their tumors.
ANK-101 is a study drug meant to stimulate the immune system to fight against cancer. The drug will be injected directly into one or more tumors every 3 weeks for up to 8 doses in case of Part 1 and Part 3 and every 6 weeks up to 4 doses in case of Part 2 NSCLC as long as the drug is helping them and reasonably safe to use. Participants in Part 3 will also receive cemiplimab in addition to ANK-101. Participants
will be instructed on how to care for their injection sites. Biopsies, imaging scans, and other tests may be repeated during study visits.
Participants will have follow-up visits 30 and 90 days after their last dose.
Participants may remain in the study for up to 10 months in case of Part 1 and Part 2 and up to 16 months in case of Part 3.
INCLUSION CRITERIA:
Participants must meet all the following criteria for inclusion:
1. Be >= 18 years of age on day of signing informed consent.
2. Have histologically or cytologically confirmed advanced solid tumor malignancy. Participants with metastatic disease will be eligible.
-Part 1 only: Tumor(s) must be cutaneous, subcutaneous, soft tissue, or nodal in locations that are visible, palpable, or detectable by ultrasound.
-Part 2 only: Participants must have at least one tumor located in deep viscera able to be accessed by interventional radiologic or endoscopic procedures for injection (e.g., ultrasound or computed tomography [CT] guided).
-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.
Note: Participants for whom the primary site of CSCC is the dry red lip (vermillion), anogenital area, or nasal mucosa are not eligible. Participants with mixed histologies will not be eligible. Surgery must be deemed contraindicated in the opinion of a Mohs dermatologic surgeon, a head and neck surgeon, or plastic surgeon. Participants must also be deemed not appropriate for radiation therapy.
3. Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the Investigator/radiology.
4. Have documented disease progression, be refractory to, or intolerant of existing SOC therapy(ies) known to provide clinical benefit for their condition (including surgical cure) or not be eligible for SOC therapy(ies).
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
6. Have a life expectancy > 12 weeks.
7. Have adequate bone marrow function defined as:
a. Absolute neutrophil count (ANC) of >= 1.5 x 10^9/L,
b. Platelet count of >= 100.0 x 10^9/L,
c. Hemoglobin of >= 9.0 g/L (with transfusion, must be >= 14 days from first dose of study drug).
8. Have adequate hepatic function defined as:
a. Serum total bilirubin <= 1.5 x upper limit of normal (ULN), unless evidence of Gilbert Syndrome, who must have total bilirubin < 3.0 mg/dL.
b. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) <= 2.5 x ULN (or <= 5 x ULN in participants with liver metastases).
9. Have adequate renal function defined as creatinine clearance >= 50 mL/min as determined by the Cockcroft-Gault equation.
10. Have baseline electrocardiogram (EKG) without evidence of acute ischemia or prolonged QTc interval > 460 msec.
11. Heterosexually active female participants of childbearing potential must agree to use at least 2 forms of highly effective methods of contraception, including at least 1 barrier method for the duration of the study and at least 60 days after the last dose of ANK-101. Women should not donate eggs during the study and for 60 days after the last dose of ANK-101.
Note: For participants enrolled in the combination cohort (Part 3), contraception must be used during the duration of the study and for at least 120 days after the last dose of cemiplimab or 60 days after the last dose of ANK-101, whichever is later.
12. All male participants who are not sterile (biologically or surgically) must commit to the use of a reliable method of birth control (condoms with spermicide), or abstinence for the duration of the study and for 60 days after the last dose of ANK-101. Male participants should not donate sperm during the study and for 60 days after the last dose of ANK-101.
Note: For participants enrolled in the combination cohort (Part 3), contraception must be used during the duration of the study and for at least 120 days after the last dose of cemiplimab or 60 days after the last dose of ANK-101, whichever is later.
13. Human immunodeficiency virus (HIV) infected participants must be on anti-retroviral therapy (ART) and have well-controlled HIV infection/disease defined as:
a. Participants on ART must have a CD4+ T-cell count > 350 cells/mm^3 at time of screening.
b. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV ribonucleic acid (RNA) level below 50 copies/mL or the lower limit of qualification (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks prior to screening.
c. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks prior to the start of ANK-101 study drug (C1D1).
14. 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 ANK-101 study drug (C1D1).
15. Resolution of all prior anticancer therapy toxicities to . Grade 1 (except for alopecia, vitiligo, or endocrinopathies managed with replacement therapy) as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) prior to start of study drug (C1D1).
Note: Participants with endocrinopathies managed with replacement therapy may enroll and may continue on adequate hormone replacement therapy.
16. Willingness to provide freshly obtained core, punch, or excisional pre- and post-treatment tumor biopsy specimens. While freshly obtained biopsies are preferred, archival tissue may be used as the baseline sample provided tissue blocks or 20 unstained slides are available, and the tissue is collected within 12 months of C1D1. Details pertaining to tumor tissue samples can be found in the Laboratory Manual.
17. In the opinion of the Investigator, participant is capable of understanding and complying with protocol requirements.
18. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
EXCLUSION CRITERIA:
Participants are to be excluded from the study if they meet any of the following criteria:
1. Have injectable tumors impinging upon major airways or blood vessels.
2. Have had prior treatment with recombinant interleukin-12 (IL-12).
3. Have received systemic therapy with immunosuppressive agents <= 28 days before the start of study drug (C1D1); topical, intranasal, intraocular, or inhaled corticosteroids, and physiologic replacement for participants with adrenal insufficiency are allowed.
4. Have received live vaccines within 28 days prior to the start of study drug (C1D1). Note: Administration of attenuated vaccines is allowed.
5. Have primary or acquired immunodeficient states (e.g., leukemia, lymphoma).
Note: Stable chronic lymphocytic leukemia not requiring treatment within 3 years prior to C1D1 is allowed.
6. A woman of childbearing potential (WOCBP) who has a positive serum pregnancy test (within 72 hours) prior to the start of study drug (C1D1) or female participant who is breastfeeding.
7. Have had prior organ or hematopoietic stem cell transplantation.
8. Have known active uncontrolled hepatitis B virus (HBV) or hepatitis C virus (HCV).
Note: Participants who test positive for anti-HCV antibody but negative for HCV RNA are considered eligible. Participants who are hepatitis B surface antigen positive (HBsAg+) and/or hepatitis B core antibody positive (HBcAb+) and have a deoxyribonucleic acid (DNA) load of < 2,000 IU/mL (10^4 copies/mL) are considered eligible.
9. HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
10. Have 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 study drug (C1D1); participants with a prior history of autoimmune disease may be eligible following discussion with and written approval from the Sponsor s Medical Monitor.
11. Have known active central nervous system (CNS) metastases. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 28 days, and without focal neurologic change or requirement of steroid treatment for at least 14 days prior to the start of ANK-101 study drug (C1D1).
12. Have 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.
13. Have uncontrolled bleeding disorders within 4 weeks prior to the start of study drug (C1D1) or known bleeding diathesis.
Part 2 only: Participants with active bleeding diathesis or requirement for therapeutic anticoagulation that cannot be interrupted or altered for procedures.
14. Have a history of hypersensitivity to compounds of similar biological composition to IL-12, aluminum hydroxide, or drugs formulated with polysorbate-20 (a component of ANK-101 formulation).
15. Have 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.
16. Have any acute or chronic psychiatric problems or substance abuse disorder that, in the opinion of the Investigator, make the participant unsuitable for participation.
17. 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.
18. Part 3 only: hypersensitivity to cemiplimab or any of its excipients or contraindications to cemiplimab per approved local labeling.