Adaptive Phase 1/2 Study of Dual-Target CAR-NK Cells in Relapsed/Refractory Small Cell Lung Cancer (SCLC)
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
Přehled studie
Postavení
Intervence / Léčba
Detailní popis
Rationale: SCLC is characterized by rapid progression, early relapse after platinum-based therapy, and antigen heterogeneity. DLL3, CD56 (NCAM1), and GD2 are frequently evaluated SCLC-associated surface targets. Dual-target CAR designs may reduce antigen-escape risk compared with single-target approaches.
Investigational products: Three off-the-shelf allogeneic CAR-NK cell products are evaluated. Each product is manufactured from healthy-donor NK cells and engineered to express a dual-target CAR plus a safety switch (e.g., inducible caspase-9) and a persistence support element (e.g., IL-15 support). The exact construct features can be adapted to the sponsor's platform.
Study schema: (1) Screening and biomarker assessment, including tumor antigen profiling for DLL3, CD56, and GD2 by immunohistochemistry (IHC) or validated equivalent assay. (2) Phase 1 dose escalation in up to three parallel arms (one arm per dual-target construct) using a modified 3+3 design to determine MTD and/or RP2D. (3) Interim construct selection based on a composite of safety (DLT rate), manufacturability/feasibility, in vivo expansion/persistence, and preliminary efficacy. (4) Phase 2 expansion cohort treated with the selected construct at RP2D to further characterize safety and estimate antitumor activity.
Conditioning and dosing: Participants receive lymphodepleting chemotherapy (e.g., fludarabine and cyclophosphamide) followed by CAR-NK infusion(s). Because NK-cell persistence can be limited, repeat dosing within a cycle is permitted (e.g., Day 0, Day 7, Day 14), and a second cycle may be allowed in responders without prohibitive toxicity.
Safety monitoring: Participants are monitored for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infusion reactions, cytopenias, infections, and other adverse events. An independent safety monitoring committee reviews cumulative safety at each dose level and prior to construct selection.
Follow-up: Clinical follow-up continues for 24 months for efficacy and late toxicity. Long-term follow-up for gene-modified cell products (up to 15 years) may be conducted per local regulatory requirements to monitor delayed adverse events
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
- Fáze 1
Kontakty a umístění
Studijní kontakt
- Jméno: shan S Lu, Phd
- Telefonní číslo: +86 13076790030
- E-mail: Seni-Lu@beijing-biotech.com
Studijní místa
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Guangdong
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Shenzhen, Guangdong, Čína, 518036
- Nábor
- Peking University Shenzhen Hospital
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Kontakt:
- Zhen J Peng, Phd
- Telefonní číslo: +86 13076790039
- E-mail: Zhen-Peng@beijing-biotech.com
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Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Paralelní přiřazení
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: DLL3/CD56 Dual-Target CAR-NK
Allogeneic dual-target CAR-NK cells targeting DLL3 and CD56 (NCAM1) following lymphodepleting chemotherapy.
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Allogeneic dual-target CAR-NK cells engineered to enhance tumor recognition and cytotoxicity against heterogeneous solid tumors.
An alkylating chemotherapy agent used as part of lymphodepleting conditioning prior to CAR-NK cell infusion to enhance cell expansion, persistence, and anti-tumor activity.
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Experimentální: DLL3/GD2 Dual-Target CAR-NK
Allogeneic dual-target CAR-NK cells targeting DLL3 and GD2 following lymphodepleting chemotherapy.
|
Allogeneic dual-target CAR-NK cells engineered to enhance tumor recognition and cytotoxicity against heterogeneous solid tumors.
An alkylating chemotherapy agent used as part of lymphodepleting conditioning prior to CAR-NK cell infusion to enhance cell expansion, persistence, and anti-tumor activity.
|
|
Experimentální: CD56/GD2 Dual-Target CAR-NK
Allogeneic dual-target CAR-NK cells targeting CD56 (NCAM1) and GD2 following lymphodepleting chemotherapy.
|
Allogeneic dual-target CAR-NK cells engineered to enhance tumor recognition and cytotoxicity against heterogeneous solid tumors.
An alkylating chemotherapy agent used as part of lymphodepleting conditioning prior to CAR-NK cell infusion to enhance cell expansion, persistence, and anti-tumor activity.
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Incidence of dose-limiting toxicities
Časové okno: 28 Days
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28 Days
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maximum tolerated dose (MTD)
Časové okno: 12 months
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maximum tolerated dose (MTD) of the drug
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12 months
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Sekundární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
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Míra objektivní odezvy
Časové okno: 12 měsíců
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12 měsíců
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Míra kontroly onemocnění
Časové okno: 12 měsíců
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12 měsíců
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Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- EB-CARNK-SCLC-014
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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