81P - A first-in-human, multiple dose and dose escalation phase I study to investigate the safety, tolerability and antitumor activity of SmarT cells plus PD-1 blocking antibodies in patients with far advanced/metastatic solid tumors

Background

Limited infiltration and exhaustion of transferred T cells are key factors impeding the development of adoptive cell immunotherapy in solid tumors. Efficient infiltration of activated T cells into tumors plays an important role in the therapeutic effect of adoptive cell immunotherapy. A tumor-penetrating peptide iRGD modified T cells (SmarT cells) were established to promote tumor-specific lymphocyte infiltration and enhanced the antitumor efficacy of PD-1 blocking strategy.

Methods

Here we report the interim analysis results of an ongoing phase 1/2 dose-escalation clinical trial of SmarT plus PD-1 mAb in patients with previously treated solid cancers (ChiCTR2200061306). The primary objective was safety for the combination of SmarT cells, low dose radiation and PD-1 mAb; secondary objectives included efficacy and dose-finding of SmarT cells.

Results

We treated 10 patients with three SmarT doses: 1.0 × 10⁹, 5.0 × 10⁹ or 10 × 10⁹ cells. The low dose radiation (1Gy) was carried out 24 hours before SmarT injection. Three patients experienced a grade 2 fever. Two patients experienced a grade anemia. No cytokine release syndrome (CRS) occurred. No grade 3 or higher treatment-related adverse events or deaths were reported. A total of three patients had stable disease (SD) and seven patients had a progressive disease (PD). The disease control rate (DCR) reached 30.0%. The median progressive free survival time (mPFS) was 71 days and the median overall survival time (mOS) was 201 days.

Conclusions

These initial results suggest that SmarT cells has promising efficacy with an acceptable safety profile in patients with heavily pretreated solid cancers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The legal committee of Nanjing Drumtower Hospital.

Funding

The funds for Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (No. 2022-LCYJ-ZD-05, B.L.).

Disclosure

All authors have declared no conflicts of interest.