Virtual Library

Start Your Search

Khashayar Asadi



Author of

  • +

    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
    • +

      P2.04-11 - Overcoming Resistance to Immunotherapy Using CVA21: Initial Results from a Phase II Study (Now Available) (ID 2070)

      10:15 - 18:15  |  Author(s): Khashayar Asadi

      • Abstract
      • Slides

      Background

      Resistance develops in most non-small cell lung (NSCLC) patients treated with anti-PD-1/anti-PD-L1 based immunotherapy. CVA21 is an oncolytic coxsackie virus that targets ICAM over-expressing tumour cells. Pre-clinical models suggest that CVA21-induced tumour lysis may enhance the clinical efficacy of the anti-PD-1 antibody Pembrolizumab by inducing immune cell infiltration in patients that lack an immune cell rich tumour microenvironment. Previously, the Keynote 200 trial of CVA21 combined with Pembrolizumab reported an ORR of 23% in immunotherapy-naive NSCLC. We report the efficacy of Pembrolizumab in combination with CVA21 in a preliminary cohort of eight pre-treated NSCLC patients with secondary resistance to prior anti-PD-1/anti-PD-L1 therapy.

      Method

      On progression of prior therapy, IV CVA21 (1x109 TCID50) was administered on days 1, 3, 5, 8, then Q3W for 6 months, in combination with Pembrolizumab (200mg IV from day 8, then Q3W for up to 24 months). Repeat biopsies were mandated prior to cycle 2 of Pembrolizumab. Tumour measurements were calculated using immune-related RECIST. PD-L1 was tested on pre- and post-treatment biopsies using SP-263 (Ventana) and reported using the tumour proportion score (TPS).

      Result

      The majority of patients were female (n=7, 88%), median age 65 years (range 55-75), seven (88%) current or former smokers, five (63%) with 3+ lines of prior treatment, and only 1 anti-PD-1/anti-PD-L1 naive. Two patients were KRAS mutant, the remaining were wild type for EGFR, ROS1, ALK and BRAF.

      Two (25%) partial responses (PR) were observed, both in anti-PD-1/anti-PD-L1 pre-treated patients. Both responders were continuing at data cut-off, 240 and 120 days since commencement. Two achieved SD (overall clinical benefit 50%) and 3 were non-evaluable (1 early non-treatment-related death, 3 awaiting first scan). Early PD at 56 days occurred in the anti-PD-1/anti-PD-L1 naive patient (n=1).

      In the two PRs, PD-L1 TPS was 25% and 60% respectively. Preliminary IHC staining of paired biopsies showed an increase in PD-L1% in 2 (33%) evaluable patients at 21 days. PD-L1 TPS ranged from <1% to 80% in pre-treatment biopsies, but was not predictive of response or benefit from combination therapy. An increase in PD-L1 was associated with a trend toward longer disease stability (median 147 days).

      Combination treatment was well-tolerated with no observed G4/5 TRAE's.

      Conclusion

      Intravenous CVA21 in combination with pembrolizumab demonstrated encouraging clinical activity in patients who had progressed on prior anti-PD-1/anti-PD-L1 therapy, regardless of PD-L1 levels.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.