skip to main content
Idioma:
Primo Search
Clear Search Box
Search in: Busca Geral
Busca Avançada
Busca por Índices

Ligand-inducible, prostate stem cell antigen (PSCA)-directed GoCAR-T cells in advanced solid tumors: Preliminary results from a dose escalation

Becerra, Carlos Roberto ; Hoof, Pamela ; Paulson, Andrew Scott ; Manji, Gulam Abbas ; Gardner, Olivia ; Malankar, Aditya ; Shaw, Joanne ; Blass, Devin ; Ballard, Brandon ; Yi, Xiaohui ; Anumula, Madhavi ; Foster, Aaron E. ; Senesac, Joseph ; Woodard, Paul

Journal of clinical oncology, 2019-02, Vol.37 (4_suppl), p.283-283 [Periódico revisado por pares]

Texto completo disponível

Citações Citado por
  • Título:
    Ligand-inducible, prostate stem cell antigen (PSCA)-directed GoCAR-T cells in advanced solid tumors: Preliminary results from a dose escalation
  • Autor: Becerra, Carlos Roberto ; Hoof, Pamela ; Paulson, Andrew Scott ; Manji, Gulam Abbas ; Gardner, Olivia ; Malankar, Aditya ; Shaw, Joanne ; Blass, Devin ; Ballard, Brandon ; Yi, Xiaohui ; Anumula, Madhavi ; Foster, Aaron E. ; Senesac, Joseph ; Woodard, Paul
  • É parte de: Journal of clinical oncology, 2019-02, Vol.37 (4_suppl), p.283-283
  • Descrição: Abstract only 283 Background: PSCA, a cell surface protein, is upregulated in many solid tumors and correlates with disease stage. BPX601 is an autologous, T-cell product engineered to contain a PSCA-CD3ζ CAR plus the small molecule rimiducid (Rim)-inducible MyD88/CD40 costimulatory domain. BPX601 is optimized for antigen-directed and independent T cell activation, proliferation and persistence, potentially enhancing efficacy in solid tumors versus traditional CARs. This first-in-human study assesses the safety, biological and clinical activity of BPX601 plus Rim in select PSCA-positive cancers. Methods: NCT02744287 is a two-part, open-label trial. Part 1 is an ongoing 3+3 cell dose escalation to identify the recommended BPX601 cell dose (Day 0) given in combination with a fixed, single Rim dose (0.4 mg/kg; Day 7). Eligibility criteria include previously treated metastatic pancreatic cancer (mPDAC) with measurable disease & positive PSCA expression. Results: Patients received only cyclophosphamide (CTX) for lymphodepletion (LD) within three days before BPX601 infusion. Nine adults have been treated across three cell dose levels (cells/kg): 1.25x10 6 (cells only), 1.25x10 6 +Rim, 2.5x10 6 +Rim. All had mPDAC with ≥ two prior therapies. Common AEs were fatigue and nausea. No DLTs, related SAEs, neurotoxicity or CRS events were reported. Rapid cell engraftment by Day 4 was observed in all patients. No evidence of LD with CTX was seen. Of six patients that received Rim: two had cell expansion 10- to 20-fold within seven days; two had cell persistence > three weeks; all had elevated serum cytokines (IP-10, TNFα) correlated with cell expansion. Best response after ≥ one scan was 4 SD ≥ eight weeks with two minor responses (not confirmed; one patient had matched CA19-9 decrease) and 2 PD. Disease control without new therapy was 16 and > 11 weeks (ongoing) in one and two patients, respectively. Conclusions: BPX601 with single-dose Rim was well-tolerated and resulted in enhanced T cell expansion and prolonged persistence in some patients despite lack of LD. Evidence of clinical benefit in this heavily pretreated mPDAC population was seen. Part 2 is planned to open soon and will include CTX/fludarabine LD to maximize engraftment as well as gastric and prostate cancers. Clinical trial information: NCT02744287.
  • Idioma: Inglês
Voltar para lista de resultados

  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

Buscando em bases de dados remotas. Favor aguardar.