Table 3.
Clinical trials of recombinant human IL-15 (rhIL-15) and its derivatives in cancer immunotherapy. i.v., intravenous; s.c., Subcutaneous; ivb, intravenous bolus; CIV, continuous intravenous infusion; BCG, Bacillus Calmette-Geurin. AML, acute myelogenous leukemia; ccRCC, clear-cell renal cell carcinoma; NSCLC, non-small cell lung cancer; SCHNC, squamous cell head and neck cancer; mRCC, metastatic renal cell cancer; CLL, chronic lymphocytic leukemia; ATL, adult T-cell leukemia; PTCL, peripheral T-cell lymphoma; CTCL, cutaneous T-cell lymphoma; ALCL, anaplastic large cell lymphoma; ALL, acute lymphoblastic leukemia; MDS, myelodysplastic syndromes; CML, chronic myelogenous leukemia; MM, multiple myeloma; GEJC, gastroesophageal junction cancers; HNSCC, advanced head and neck squamous cell carcinoma; NMIBC, non-muscle-invasive bladder cancer; mPC, metastatic prostate cancer; SCLC, small cell lung cancer; MCC, merkel cell carcinoma; NHL, non-Hodgkin lymphoma; CRC, colorectal carcinoma; sSCC, cutaneous squamous cell carcinoma; ASCC, anal cell carcinoma.
| Clinical Trial | Agent | Description | Malignancies | Institution |
|---|---|---|---|---|
| NCT01385423 | rhIL-15 | i.v. IL-15 in combination with haploidentical donor NK cells | AML; Myelodysplastic Syndrome | Masonic Cancer Center, University of Minnesota |
| NCT02395822 | rhIL-15 | s.c. IL-15 in combination with donor IL-15 activated NK cells | AML | Masonic Cancer Center, University of Minnesota |
| NCT04150562 | rhIL-15 | i.v. IL-15 in combination with avelumab | ccRCC | National Cancer Institute |
| NCT01727076 | rhIL-15 | Efficacy and dose escalation study of IL-15 administered s.c. | Advanced Melanoma; Kidney Cancer; NSCLC; SCHNC | National Cancer Institute |
| NCT01021059 | rhIL-15 | Safety and dose escalation study of Il-15 (i.v.) | Metastatic Malignant Melanoma; mRCC | National Cancer Institute |
| NCT01369888 | rhIL-15 | Safety and dosage study of IL-15 administered (ivb) following lymphodepleting chemotherapy and adoptive cell transfer of TILs | Metastatic Melanoma | National Cancer Institute |
| NCT01572493 | rhIL-15 | Continuous intravenous infusion (CIV) of IL-15 | Lymphoma; Carcinoma | National Cancer Institute |
| NCT03759184 | rhIL-15 | CIV of IL-15 in combination with obinutuzumab | CLL | National Cancer Institute |
| NCT04185220 | rhIL-15 | CIV of IL-15 in combination with mogamulizmab | Adult T-cell Lymphoma/Leukemia; Sezary Syndrome; Mycosis Fungoides | National Cancer Institute |
| NCT03388632 | rhIL-15 | Safety and dosage study of IL-15 (s.c.) in combination with checkpoint inhibitors nivolumab or ipilimumab or both | Metastatic Solid Tumors; Treatment-Refractory Cancers | National Cancer Institute |
| NCT02689453 | rhIL-15 | Dosage, safety, and efficacy study of IL-15 (s.c.) in combination with alemtuzumab | Relapsed T-cell Lymphoma; ATL; PTCL; CTCL; T-cell Prolymphocytic Leukemia | National Cancer Institute |
| NCT03905135 | rhIL-15 | CIV of IL-15 in combination with avelumab (Bacenico) | Peripheral T-cell Lymphoma; Mycosis Fungoides; Sezary Syndrome; ALCL | National Cancer Institute |
| NCT01875601 | rhIL-15 | Toxicity and dose escalation study of IL-15 in combination with NK cell infusion following lymphodepletion, analysis of pharmacokinetics in pediatric patients, and anti-tumor efficacy | Solid Tumors; Brain Tumors; Sarcoma; Pediatric Cancers; Neuroblastoma | National Cancer Institute |
| NCT02452268 | NIZ985 | Dose escalation and expansion study oNIZ985 and NIZ985 (s.c.) in combination with PDR001 | Metastatic and Advanced Solid Tumors | Novartis Pharmaceuticals |
| NCT02452268 | NIZ985 | Dose escalation and expansion study of NIZ985 and NIZ985 (s.c.) in combination with spartalizumab | In escalation: solid tumors and lymphoma In expansion: melanoma |
Novartis Pharmaceuticals |
| NCT01885897 | N-803 | Dose escalation and extended study of ALT-803 (i.v.) | AML; ALL; MDS; Lymphoma;CLL; CML | Masonic Cancer Center, University of Minnesota |
| NCT02099539 | N-803 | Dose escalation study of N-803 (i.v. vs. s.c.) | Relapsed or Refractory MM | Altor BioScience |
| NCT03853317 | N-803 | N-803 in combination with off-the-shelf CD16 targeted NK cells (haNK) and avelumab | Merkel Cell Carcinoma | ImmunityBio Incorporated |
| NCT02989844 | N-803 | N-803 for the maintenance after allogeneic hematopoietic cell transplant (alloHCT) | AML; MDS | Masonic Cancer Center, University of Minnesota |
| NCT04847466 | N-803 | Efficacy study of irradiated PD-L1 CAR-NK cells combined with pembrolizumab and N-803 (s.c.) | GEJ; HNSCC | National Cancer Institute |
|
NCT03022825 NCT02138734 |
N-803 | BCG in combination with N-803 or BCG alone or N-803 alone administered via intravesical instillation | NMIBC | ImmunityBio Incorporated |
| NCT04247282 | N-803 | TriAd vaccine in combination with N-803 (s.c.) | Head and Neck Cancer Head and Neck Neoplasms |
National Cancer Institute |
| NCT03493945 | N-803 | 2-. 3-, or 4 4-drug combinations of M7824, BN-brachyury vaccine, N-803 and Epacodstat | mPC; Prostate Cancer; Prostate Neoplasm; Solid Tumors | National Cancer Institute |
| NCT03520686 | N-803 | N-803 (s.c.) in combination with either pembrolizumab, carboplatin + nab-paclitaxel + pembrolizumab, or cisplatin + carboplatin + nab-paclitaxel + pembrolizumab | NSCLC | ImmunityBio Incorporated |
| NCT05096663 | N-803 | N-803 (s.c.) in combination with pembrolizumab in comparison to standard care therapy a | Advanced NSCCLC | Southwest Oncology Group |
| NCT04491955 | N-803 | N-803 (s.c.) in combination with CV301 vaccine, M7824, and NHS-IL12 | Small Bowel Cancers Colorectal Cancers |
National Cancer Institute |
| NCT04927884 | N-803 | N-803 in combination with sacituzumab | Advanced Triple Negative Breast Cancer | ImmunityBio Incorporated |
| NCT04898543 | N-803 | N-803 (s.c.) in combination with memory-cytokine enriched NK (m-ceNK) cells | Metastatic Solid Tumors | ImmunityBio Incorporated |
| NCT04290546 | N-803 | N-803 (s.c.) in combination with cytokine-induced memory-like (CIML) NK-enriched cells | HNSCC | Dana-Farber Cancer Institute |
| NCT03003728 | N-803 | N-803 (s.c.) in combination with elotuzumab, melphalan, and expanded NK cell autologous stem cell transplantation | MM | University of Arkansas |
| NCT02559674 | N-803 | Dose escalation study of N-803 (s.c.) in combination with gemcitabine and nab-paclitaxel | Advanced Pancreatic Cancer | Altor BioScience |
| NCT03228667 | N-803 | PD-1/PD-L1 checkpoint inhibitors in combination with N-803 and subsequently combined with PD-L1t-haNK cell therapy in patients with prior treatment of PD-1/PD-L1 checkpoint inhibitors | NSCLC; SCLC; Urothelial Carcinoma; HNSCC; MCC; Melanoma; RCC; Gastric Cancer; Cervical Cancer; and others | ImmunityBio Incorporated |
| NCT04659629 | NL-201 | Safety study of NL-201 (i.v.) alone or in combination with pembrolizumab | Solid Tumor Cancers | Neoleukin Therapeutics Incorporated |
| NCT04136756 | NKTR-255 | NKTR-255 (i.v.) IL-15 receptor agonist alone or in combination with daratumumab or rituximab | MM; NHL; Indolent Non-Hodgkin Lymphoma | Nektar Theraputics |
| NCT05327530 | NKTR-255 | NKTR-255 (i.v.) IL-15 receptor agonist in combination with avelumab | Locally Advanced or Metastatic Urothelial Carcinoma | EMD Serono Research and Development Institute Incorporated |
| NCT04616196 | NKTR-255 | NKTR-255 (i.v.) IL-15 receptor agonist alone or in combination with cetuximab | HNSCC; CRC; cSCC; ASCC; Cerivcal Cancer | Nektar Theraputics |
| NCT05359211 | NKTR-255 | NKTR-255 (i.v.) IL-15 receptor agonist in combination with autologous CD19-CAR T cells | B-Cell Lymphoma | Fred Hutchinson Cancer Center |