AACR 2019—Mesothelin CAR T-cell therapy shows benefit in solid pleural tumors


  • Keren Landman, MD
  • Univadis
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Takeaway

  • Intrapleurally administered mesothelin-targeted (MSLN) chimeric antigen receptor (CAR) T-cells demonstrated activity against solid pleural tumors in a small group of patients.

Why this matters

  • CAR T-cell therapy is effective against hematological malignancies, but applications in solid cancers have been limited.
  • Although pleural cancers are aggressive tumors, the last FDA-therapy approved for this disease in the early 2000's only conferred OS and PFS benefit of 3 months.

Study design

  • Phase 1 study of patients with malignant pleural disease expressing mesothelin; 40% had received at least 3 prior therapy lines.
  • 21 patients received 1 dose of CD2-costimulated, mesothelin-targeted, fully human CAR T-cells with the iCaspase-9 safety gene, administered intrapleurally with (18) or without (3) cyclophosphamide.
  • 6-17 weeks later, 14 patients received anti-PD1 agents off-protocol.
  • Funding sources: NCI, DoD, SU2C, Baker Street Foundation.

Key results

  • Response rate was 72% among 11 patients who received cyclophosphamide, CAR T-cells, and ≥3 doses of anti-PD1 with at least 3 months' follow-up: 2 had complete response, 5 had partial response, 4 had stable disease.
  • No on-target, off-tumor toxicities and no evidence of immunogenicity were detected.
  • There were no >grade 2 toxicities, although 1 patient had febrile neutropenia related to cyclophosphamide.

Limitations

  • Phase 1 trial; long-term efficacy not established.