Recombinant Interleukin-15 in Combination With Checkpoint Inhibitors Nivolumab and Ipilimumab in People With Refractory Cancers
Metastatic Solid Tumors · Treatment-Refractory Cancers
Bottom Line
View on ClinicalTrials.gov: NCT03388632 ↗Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- rhIL-15 (Drug); Ipilimumab (Drug); Nivolumab (Drug); Tumor biopsies (Procedure); EKG (Diagnostic_test); ECHO (Diagnostic_test); CT Scan (Diagnostic_test)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Nov 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) at Which Dose-Limiting Toxicities (DLT) Occurred With rhIL-15 Administered in Combination With Fixed Doses of Nivolumab and Ipilimumab |
1.0 | — |
| PRIMARY Number of Dose-limiting Toxicities (DLT) Possibly, Probably, or Definitely Related to Study Drugs |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants Experiencing Dose-Limiting Toxicities (DLT) |
0; 0; 0; 0; 1; 1 | — |
| SECONDARY Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0) |
2; 1; 2; 2; 18; 2 | — |
Summary
Eligibility Criteria
- INCLUSION CRITERIA:
Subjects must have histologically confirmed solid tumor malignancy that is metastatic or treatment refractory cancers which are not curable or do not have known measures or treatments that are associated with a survival advantage (as defined by the subject or the physician investigator). Enrollment of subjects with tumors that can be safely biopsied is encouraged.
Subjects must have evaluable, or measurable disease defined as greater than or equal to 1 lesion that can be accurately measured in greater than or equal to 1 dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with a spiral computed tomography (CT) scan.
Subjects must have recovered to less than or equal to grade 1 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) or stabilized from toxicity of prior chemotherapy or biologic therapy administered more than 4 weeks or 5 half-lives earlier, whichever is shorter.
Subjects on bisphosphonates/denosumab for any cancer or on hormone therapy for prostate cancer may continue this therapy. However, subjects with prostate cancer must have confirmed metastatic disease that has progressed despite hormonal therapy or refused or is intolerant of hormonal therapy.
Age greater than or equal to 18 years.
Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2 (Karnofsky or Lansky greater than or equal to 70%.
Subjects must have normal organ and marrow function as defined below:
- Leukocytes greater than or equal to 2,000/mm^3
- Absolute neutrophil count (ANC) greater than or equal 1,500/mm^3
- Platelets greater than or equal to 100,000/mm^3
- Total bilirubin less than or equal to 1.5 times institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than or equal to 1.5 times institutional upper limit of normal (ULN) or if liver metastasis, less than or equal to 2.5 times ULN
- Serum creatinine less than or equal to 1.5 times institutional ULN, OR Creatinine clearance greater than or equal to 50 mL/min/1.73 m^2 for subjects with serum creatinine levels greater than 1.5 times higher than institutional normal
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
Subjects with inactive central nervous system (CNS) metastasis are eligible. Inactive CNS metastasis is defined as: no symptoms of brain metastases after successful definitive treatment of brain metastases (surgical resection, whole brain irradiation, stereotactic radiation therapy, or a combination of these) with stable or improved radiographic appearance on magnetic resonance imaging (MRI) scan at least 1 month after completion of treatment.
Subjects may have previously progressed on treatment with one of the 3 agents being used in this trial or treatment with other checkpoint inhibitors, as long as they have recovered from previous toxicity. Subjects that previously progressed on treatment with a combination of any 2 of the 3 agents being used in this trial are eligible for the triplet cohort only.
The effects of ipilimumab, nivolumab, and rhIL-15 on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, during the treatment portion of the study, and for a minimum for 5 months (women) and 7 months (men) after the last dose of study drug. Should a woman become pregnant or suspect she is pregnant while she o
Data sourced from ClinicalTrials.gov (NCT03388632). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.