Phase 1/2 Study of EB-NK-301 (Allogeneic TROP2-CAR NK Cells) in Advanced TROP2-Expressing Solid Tumors (SOLID-NK)
A Phase 1/2, Open-Label, Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Tolerability, and Preliminary Anti-tumor Activity of EB-NK-301 (Allogeneic TROP2-Targeted CAR NK Cells) Following Lymphodepleting Chemotherapy in Adults With Advanced or Metastatic TROP2-Expressing Solid Tumors
study evaluates EB-NK-301, an investigational off-the-shelf allogeneic CAR-NK cell product targeting TROP2, in adults with advanced or metastatic solid tumors that express TROP2 and have progressed after standard therapy.
The primary goals are to assess safety and tolerability, identify dose-limiting toxicities (DLTs), and determine a recommended Phase 2 dose (RP2D). Secondary goals include preliminary anti-tumor activity, persistence of infused CAR-NK cells, and exploratory immune biomarkers.
Studieoversikt
Status
Intervensjon / Behandling
Detaljert beskrivelse
Study Overview: The study includes two parts. Part A (dose escalation) uses a standard dose-escalation design to evaluate multiple dose levels of EB-NK-301 after lymphodepleting chemotherapy. Part B (dose expansion) enrolls additional participants at the selected RP2D to further characterize safety and to estimate preliminary efficacy within selected tumor-type cohorts.
Treatment Plan: Participants receive lymphodepleting chemotherapy (fludarabine and cyclophosphamide) followed by intravenous EB-NK-301 infusions. Participants are monitored closely for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infusion reactions, and other adverse events.
Assessments: Tumor imaging is performed every 8 weeks during the first 12 months, then every 12 weeks as clinically indicated. Blood samples are collected to assess CAR-NK cell persistence, cytokines, and other immune biomarkers.
Follow-up: Participants are followed for safety and survival for up to 24 months after first infusion.
Studietype
Registrering (Antatt)
Fase
- Fase 2
- Fase 1
Kontakter og plasseringer
Studiekontakt
- Navn: shan S Lu, Phd
- Telefonnummer: +86 13076790030
- E-post: Seni-Lu@beijing-biotech.com
Studiesteder
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Guangdong
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Shenzhen, Guangdong, Kina, 518036
- Rekruttering
- Peking University Shenzhen Hospital
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Ta kontakt med:
- Zhen J Peng, Phd
- E-post: Zhen-Peng@beijing-biotech.com
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
Inclusion Criteria:
- Age 18 to 75 years at the time of informed consent.
- Histologically or cytologically confirmed advanced or metastatic solid tumor with documented TROP2 expression (per local testing or central confirmation).
- Disease progression on, intolerance to, or ineligibility for available standard therapy.
- At least one measurable lesion per RECIST 1.1.
- ECOG performance status 0 to 1.
- Adequate organ function (hematologic, renal, hepatic) within protocol-defined limits.
- Life expectancy ≥ 12 weeks.
- Willingness to use effective contraception during study participation and for a protocol-defined period after last infusion (if of childbearing potential).
- Ability to understand and willingness to sign written informed consent.
Exclusion Criteria:
- Active central nervous system (CNS) metastases or leptomeningeal disease (unless treated and clinically stable for ≥ 4 weeks).
- Prior allogeneic hematopoietic stem cell transplant or solid organ transplant.
- Uncontrolled active infection, including uncontrolled hepatitis B, hepatitis C, or HIV infection.
- Active autoimmune disease requiring systemic immunosuppression.
- Clinically significant cardiovascular disease (e.g., recent myocardial infarction or stroke within 6 months, uncontrolled arrhythmia).
- Receipt of another investigational agent within 2 weeks (or 5 half-lives, whichever is longer) prior to lymphodepleting chemotherapy.
- Prior gene-modified cellular therapy within 3 months prior to enrollment.
- Systemic corticosteroid therapy > 10 mg/day prednisone equivalent within 7 days prior to lymphodepletion (excluding physiologic replacement).
- Pregnant or breastfeeding.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Sekvensiell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: Dose Escalation
Sequential dose escalation of EB-NK-301 following lymphodepleting chemotherapy to evaluate safety, DLTs, and identify RP2D.
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Investigational allogeneic CAR-NK cell product targeting TROP2, administered by intravenous infusion.
Andre navn:
Lymphodepleting chemotherapy administered prior to EB-NK-301 infusion to facilitate immune cell engraftment and persistence.
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Eksperimentell: Dose Expansion
Expansion cohorts at the RP2D in selected TROP2-expressing tumor types to further assess safety and preliminary efficacy.
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Investigational allogeneic CAR-NK cell product targeting TROP2, administered by intravenous infusion.
Andre navn:
Lymphodepleting chemotherapy administered prior to EB-NK-301 infusion to facilitate immune cell engraftment and persistence.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Incidence of dose-limiting toxicities (DLTs) (CTCAE v5.0)
Tidsramme: 28 days
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28 days
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Incidence and severity of treatment-emergent adverse events (AEs)
Tidsramme: 12 months
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12 months
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Recommended Phase 2 dose (RP2D) of EB-NK-301
Tidsramme: 6 months
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6 months
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Sekundære resultatmål
Resultatmål |
Tidsramme |
|---|---|
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Total overlevelse (OS)
Tidsramme: 24 måneder
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24 måneder
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Varighet av respons (DoR)
Tidsramme: 24 måneder
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24 måneder
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Objective response rate (ORR) per RECIST 1.1
Tidsramme: 12 months
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12 months
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Samarbeidspartnere og etterforskere
Sponsor
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- EB-NK-SOLID-019
Legemiddel- og utstyrsinformasjon, studiedokumenter
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