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
Studienübersicht
Status
Intervention / Behandlung
Detaillierte Beschreibung
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
Studientyp
Einschreibung (Geschätzt)
Phase
- Phase 2
- Phase 1
Kontakte und Standorte
Studienkontakt
- Name: shan S Lu, Phd
- Telefonnummer: +86 13076790030
- E-Mail: Seni-Lu@beijing-biotech.com
Studienorte
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Guangdong
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Shenzhen, Guangdong, China, 518036
- Rekrutierung
- Peking University Shenzhen Hospital
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Kontakt:
- Zhen J Peng, Phd
- Telefonnummer: +86 13076790039
- E-Mail: Zhen-Peng@beijing-biotech.com
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Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
- Erwachsene
- Älterer Erwachsener
Akzeptiert gesunde Freiwillige
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Nicht randomisiert
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
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Experimental: 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.
|
|
Experimental: DLL3/GD2 Dual-Target CAR-NK
Allogeneic dual-target CAR-NK cells targeting DLL3 and GD2 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.
|
|
Experimental: 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.
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
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Incidence of dose-limiting toxicities
Zeitfenster: 28 Days
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28 Days
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|
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maximum tolerated dose (MTD)
Zeitfenster: 12 months
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maximum tolerated dose (MTD) of the drug
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12 months
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Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Objektive Rücklaufquote
Zeitfenster: 12 Monate
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12 Monate
|
|
Seuchenkontrollrate
Zeitfenster: 12 Monate
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12 Monate
|
Mitarbeiter und Ermittler
Sponsor
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Tatsächlich)
Primärer Abschluss (Geschätzt)
Studienabschluss (Geschätzt)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Pathologische Prozesse
- Neubildungen nach Standort
- Neubildungen
- Krankheitsattribute
- Erkrankungen der Atemwege
- Lungenkrankheit
- Neubildungen der Atemwege
- Thoraxneoplasmen
- Lungentumoren
- Karzinom, bronchogen
- Bronchiale Neubildungen
- Pathologische Zustände, Anzeichen und Symptome
- Wiederauftreten
- Kleinzelliges Lungenkarzinom
Andere Studien-ID-Nummern
- EB-CARNK-SCLC-014
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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