A Phase 2 study of In Situ Oncolytic Virus Therapy and Stereotactic Body Radiation Therapy Followed by Pembrolizumab in Metastatic Non-Small Cell Lung Cancer
Mené sur 28 patients atteints d'un cancer du poumon métastatique non à petites cellules, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, d'un traitement combinant un virus oncolytique exprimant la thymidine kinase du virus Herpes simplex (ADV/HSV-tk), une radiochirurgie et du pembrolizumab
Purpose: A phase 2 study of stereotactic body radiation therapy and in situoncolytic virus therapy in metastatic non-small cell lung cancer (mNSCLC) followed by Pembrolizumab (STOMP) was designed to explore the dual approach in enhancing single pembrolizumab with ADV/HSV-tk plus valacyclovir gene therapy and stereotactic radiotherapy (SBRT) in mNSCLC. Methods: STOMP is a single-arm, open-label phase II study. Patients with mNSCLC received intratumoral injections of ADV/HSV-tk (5 × 1011 vp) and SBRT (30 Gy in 5 fractions) followed by pembrolizumab 200 mg IV every 3 weeks until disease progression or intolerable toxicity. The primary end point was ORR (CR and PR). Secondary end points included clinical benefit rate (CBR, CR, PR and SD), PFS, OS and safety. Results: 28 patients were enrolled, among which 27 were evaluated for response. The ORR was 33.3% including two CR (7.4%) and seven PR (25.9%). CBR was 70.4%. 6/8 (75.0%) patients who were immune checkpoint inhibitor (ICI) refractory derived clinical benefits. Responders had durable responses with median PFS, and OS not reached. While the total population had a median PFS of 7.4 months (95% CI, 5.1 to 9.6 months), and OS 18.1 months (95%CI, 15.4 to 20.9 months). The combination was well tolerated with Grade 3 or higher toxicity in 6 (21.4%) patients. Conclusion: Dual approach of in situ ADV/HSV-tk plus valacyclovir gene therapy and SBRT as a chemotherapy sparing strategy to enhance anti-tumor effect of pembrolizumab is a well-tolerated encouraging treatment in patients with mNSCLC.
International Journal of Radiation Oncology, Biology, Physics 2023