Overview
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.
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.
Eligibility
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.