Adaptive Phase 1/2 testing dual-target CAR‑NK cells for relapsed or refractory small cell lung cancer
A Phase 1/2 Adaptive Dose-Escalation and Expansion Study of Dual-Targeting Chimeric Antigen Receptor Natural Killer (CAR-NK) Cells Directed Against DLL3, CD56 (NCAM1), and/or GD2 in Adults With Relapsed/Refractory Small Cell Lung Cancer
This trial tests off-the-shelf dual-target CAR‑NK cell therapy in adults with relapsed or refractory extensive-stage small cell lung cancer to see if it is safe and can shrink tumors.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | CAR-T, prednisone, chemotherapy, cyclophosphamide, fludarabine |
| Locations | 1 site (Shenzhen, Guangdong) |
| Trial ID | NCT07480213 on ClinicalTrials.gov |
What this trial studies
This open-label, multi-center adaptive Phase 1/2 trial gives allogeneic off-the-shelf CAR‑NK cell products that target two antigens to adults with relapsed or refractory extensive-stage SCLC. Three dual-target constructs (DLL3/CD56, DLL3/GD2, and CD56/GD2) are evaluated in parallel during a modified 3+3 dose-escalation to determine the maximum tolerated dose or recommended Phase 2 dose. Tumor antigen profiling by immunohistochemistry guides baseline characterization and an interim composite assessment of safety, manufacturability, in vivo persistence, and early antitumor activity selects one construct to move into a Phase 2 expansion cohort. Participants receive lymphodepleting chemotherapy (for example fludarabine and cyclophosphamide) before CAR‑NK infusion(s), and repeat dosing may be used to support NK persistence.
Who should consider this trial
Good fit: Adults 18–75 with histologically confirmed relapsed or refractory extensive-stage SCLC who have had at least one prior systemic regimen (typically including a platinum), have measurable disease, ECOG 0–1, adequate organ function, and available tumor tissue for antigen profiling are the intended candidates.
Not a fit: Patients with uncontrolled or symptomatic central nervous system metastases, poor organ function, ECOG >1, inability to undergo lymphodepleting chemotherapy, or who are pregnant are unlikely to be eligible or to benefit.
Why it matters
Potential benefit: If successful, this approach could offer an off‑the‑shelf cell therapy that better controls relapsed SCLC by targeting two tumor antigens and reducing antigen‑escape.
How similar studies have performed: Early-phase CAR‑NK studies and dual-target CAR designs have shown acceptable safety and occasional responses in small cohorts, but dual-target CAR‑NK therapy specifically for SCLC is largely novel with limited prior clinical evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age 18 to 75 years at the time of consent. * Histologically or cytologically confirmed small cell lung cancer (SCLC) that is metastatic, extensive-stage, or unresectable, and relapsed or refractory after at least 1 prior systemic regimen (must include a platinum-based regimen unless contraindicated). * At least one measurable lesion per RECIST v1.1. * ECOG performance status 0 to 1. * Adequate organ function (hematologic, renal, hepatic, and cardiac) as defined in the protocol (examples: ANC \>= 1.0 x10\^9/L, platelets \>= 75 x10\^9/L, creatinine clearance \>= 50 mL/min, AST/ALT \<= 3 x ULN, total bilirubin \<= 1.5 x ULN). * Life expectancy \>= 12 weeks. * Tumor tissue available (archival or fresh) for antigen profiling (DLL3, CD56/NCAM1, GD2). * Negative pregnancy test for persons of childbearing potential; agreement to use effective contraception for the protocol-defined duration. Exclusion Criteria: * Active or uncontrolled CNS metastases or leptomeningeal disease (treated/stable CNS metastases may be allowed per protocol). * Prior treatment with CAR-T, CAR-NK, or other gene-modified cellular therapy within 6 months (or any prior therapy directed against the investigational target antigens if it would confound safety/efficacy assessment). * Allogeneic hematopoietic stem cell transplant within 6 months or active graft-versus-host disease. * Active uncontrolled infection, including uncontrolled HIV, active hepatitis B or C with viremia, or active tuberculosis. * Clinically significant cardiovascular disease (e.g., recent myocardial infarction within 6 months, uncontrolled arrhythmia, LVEF \< 45%). * Active autoimmune disease requiring systemic immunosuppression; chronic systemic corticosteroid use \> 10 mg/day prednisone equivalent (unless for physiologic replacement). * Concurrent malignancy requiring active treatment (exceptions may apply for certain non-melanoma skin cancers or in situ cancers). * Pregnant or breastfeeding. * Any condition that, in the investigator's opinion, would make participation unsafe or interfere with compliance.
Where this trial is running
Shenzhen, Guangdong
- Peking University Shenzhen Hospital — Shenzhen, Guangdong, China (Recruiting)
Study contacts
- Study coordinator: Seni S Lu, Phd
- Email: Seni-Lu@beijing-biotech.com
- Phone: +86 13076790030
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.