This study is NOT currently recruiting participants.
Number
001924-C
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Recruitment has not started Gender: Male & Female Min Age: 18 Years Max Age: 120 Years
Referral Letter Required
No
Population Exclusion(s)
Children;Fetuses;Neonates;Pregnant Women
Keywords
Nodal Tumors; Soft tissue tumors; Intratumoral Injection; Immunotherapy
Recruitment Keyword(s)
None
Condition(s)
Tumors; Neoplasms; Cancer of Skin
Investigational Drug(s)
ANK-101
Investigational Device(s)
Intervention(s)
Biological/Vaccine: ANK-101
Supporting Site
National Cancer Institute
Cancer is the second leading cause of death worldwide. Cancer-related deaths decreased by 31% between 1991 and 2018, but better treatments are still needed.
Objective:
To test a study drug (ANK-101) in people with advanced cancer.
Eligibility:
People aged 18 years and older with advanced tumors that can be seen or felt through the skin. Their tumor(s) must be detectable by ultrasound and accessible for injection.
Design:
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 some or all of a participant s tumors once every 3 weeks for up to 8 doses. 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 as long as the drug is helping them.
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INCLUSION CRITERIA: All participants must meet the following criteria for inclusion: 1. Be >= 18 years of age on day of signing informed consent. 2. Have histologically or cytologically confirmed diagnosis of cutaneous, subcutaneous, soft tissue, or nodal advanced solid tumor malignancy. Participants with metastatic disease will be eligible. 3. Have measurable disease per RECIST v1.1 as assessed by the Investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. 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 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). 4. Have documented disease progression, be refractory to, or intolerant of existing SOC therapy(ies) known to provide clinical benefit for their condition 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 >= 28 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. 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. 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 treatment (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 treatment (C1D1). 15. Resolution of all prior anticancer therapy toxicities (except for alopecia or vitiligo) to <= Grade 1 (as per NCI CTCAE Version 5.0). Note: Participants previously treated with immunotherapy who have endocrinopathies 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 ANK-101 treatment (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 ANK-101 treatment (C1D1). Note: Administration of attenuated vaccines is allowed. 5. Have primary or acquired immunodeficient states (e.g., leukemia, lymphoma). 6. A woman of childbearing potential (WOCBP) who has a positive serum pregnancy test (within 72 hours) prior to the start of ANK-101 treatment (C1D1) or female participant who is breastfeeding. 7. Have had prior organ transplantation. 8. Have 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 ANK-101 treatment (C1D1). 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 ANK-101 treatment (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 treatment (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 ANK-101 treatment (C1D1) or known bleeding diathesis. 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.
All participants must meet the following criteria for inclusion:
1. Be >= 18 years of age on day of signing informed consent.
2. Have histologically or cytologically confirmed diagnosis of cutaneous, subcutaneous, soft tissue, or nodal advanced solid tumor malignancy. Participants with metastatic disease will be eligible.
3. Have measurable disease per RECIST v1.1 as assessed by the Investigator/radiology. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
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 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).
4. Have documented disease progression, be refractory to, or intolerant of existing SOC therapy(ies) known to provide clinical benefit for their condition 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 >= 28 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.
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.
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 treatment (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 treatment (C1D1).
15. Resolution of all prior anticancer therapy toxicities (except for alopecia or vitiligo) to <= Grade 1 (as per NCI CTCAE Version 5.0).
Note: Participants previously treated with immunotherapy who have endocrinopathies 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 ANK-101 treatment (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 ANK-101 treatment (C1D1). Note: Administration of attenuated vaccines is allowed.
5. Have primary or acquired immunodeficient states (e.g., leukemia, lymphoma).
6. A woman of childbearing potential (WOCBP) who has a positive serum pregnancy test (within 72 hours) prior to the start of ANK-101 treatment (C1D1) or female participant who is breastfeeding.
7. Have had prior organ transplantation.
8. Have 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 ANK-101 treatment (C1D1).
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 ANK-101 treatment (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 treatment (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 ANK-101 treatment (C1D1) or known bleeding diathesis.
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.
Principal Investigator
Referral Contact
For more information: