Bladder Cancer, Breast Cancer (Locally Advanced or Metastatic), Cancer, Colorectal Cancer, Esophageal Cancer, Glioblastoma, Kidney Cancer, Leukaemia, Liver Cancer (Primary and Metastatic), Lung Cancer (Diagnosis), Melanoma (Skin Cancer), Non-Melanoma Skin Cancer, Ovarian Cancer, Pancreatic Cancer Metastatic, Sarcoma
Conditions
Keywords
Natural killer cells, NK cell therapy, Solid tumors, IL-15, Breast Cancer, Lung and Bronchus Cancer, Prostate Cancer, Colorectal (Colon and Rectal) Cancer, CAR-T, Non-Melanoma Skin Cancer, Melanoma, Bladder Cancer, Kidney (Renal Cell and Renal Pelvis) Cancer, Pancreatic Cancer, Stomach (Gastric) Cancer, Esophageal Cancer
Brief summary
This Phase 1/2 study evaluates the safety, tolerability, and preliminary anti-tumor activity of EBNK-001 (allogeneic NK cells) given after lymphodepleting cyclophosphamide/fludarabine (CY/FLU) and supported with low-dose IL-15, administered either alone or in combination with pembrolizumab in adults with advanced/metastatic solid tumors. The study will determine a recommended Phase 2 dose (RP2D) and explore signals of clinical activity using RECIST-based response criteria.
Detailed description
EBNK-001 is an "off-the-shelf" allogeneic NK cell product intended for multi-dose administration. Participants first receive a short course of lymphodepleting chemotherapy (CY/FLU) to facilitate NK-cell expansion and persistence, followed by weekly NK-cell infusions for 3 consecutive weeks in each treatment cycle (e.g., Days 1, 8, 15). Low-dose IL-15 is administered after NK-cell infusion(s) to support NK-cell survival. The trial includes: Phase 1 (Dose Escalation): evaluates escalating doses of EBNK-001 to identify MTD/RP2D based on DLTs observed in the first 28 days after first NK-cell infusion (DLT window). Phase 2 (Dose Expansion): evaluates preliminary efficacy at RP2D in selected solid tumor expansion cohorts. Participants are followed for tumor response until progression and for survival for at least 12 months. If EBNK-001 is considered a gene-modified cell product in your program, participants may transition into a separate long-term follow-up study consistent with long-term monitoring described in NK cell therapy protocols.
Interventions
BIOLOGICALEBNK-001 + IL-15 + Pembrolizumab
Biological: EBNK-001 (Allogeneic NK Cells) Dose levels (example): 1×10\^8; 3×10\^8; 9×10\^8 viable cells/infusion Schedule: weekly infusions on Days 1, 8, and 15 (per cycle) Drug: Cyclophosphamide (CY) lymphodepletion: 300 mg/m² IV daily ×2 days (Cycle 1 only) Drug: Fludarabine (FLU) Example lymphodepletion: 25 mg/m² IV daily ×2 days (Cycle 1 only) Drug: Interleukin-15 (IL-15) Low-dose IL-15 given after NK cell infusion to support NK cell survival dose used in NK protocols: 6 MIU per dose Drug: Pembrolizumab Pembrolizumab administered per standard prescribing schedule
Sponsors
Essen Biotech
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1 dose-escalation to determine MTD/RP2D using DLT monitoring in an initial safety window (commonly \ 28 days). Phase 2 expansion cohorts at RP2D to estimate preliminary efficacy in selected solid tumor types.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years. * Histologically confirmed advanced/metastatic solid tumor that is relapsed/refractory after standard therapy (or no standard therapy available). * Measurable disease per RECIST v1.1 (or iRECIST if applicable). * ECOG performance status 0-1 (or 0-2 as allowed). * Adequate organ function (thresholds modeled on NK protocols): * Platelets ≥ 75,000/µL; hemoglobin ≥ 9 g/dL; ANC ≥ 1,000/µL (unsupported by growth factors/transfusions as defined). * eGFR ≥ 60 mL/min/1.73m². * AST/ALT ≤ 3× ULN. * Oxygen saturation ≥ 90% on room air (with PFT requirements if indicated). * LVEF ≥ 40% (by ECHO/MUGA/CMR). * If brain metastases are present, they must be stable for a defined period (example: ≥3 months) and not requiring escalating steroids.
Exclusion criteria
* Pregnant or breastfeeding. * Any condition requiring systemic immunosuppression (e.g., \>5 mg prednisone/day or equivalent) during dosing window (topical/inhaled may be allowed). * Active autoimmune disease requiring systemic immunosuppression. * Uncontrolled bacterial, fungal, or viral infection. * Receipt of investigational agent within 28 days before first study drug. * Live vaccine within 6 weeks prior to lymphodepletion. * Known HIV positivity or active hepatitis B/C with detectable viral load (protocol may allow chronic asymptomatic hepatitis depending on risk plan). * Known allergy to investigational product components (example: albumin/human or DMSO). * Any medical/social condition likely to interfere with study compliance or increase risk.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) | 30 DAYS | — |
| Incidence of Dose-Limiting Toxicities (DLTs) | 30 DAYS | Incidence of Dose-Limiting Toxicities (DLTs) |
Countries
China
Contacts
CONTACTRhoda M Smith, Phd
Outcome results
None listed