Objective response rate among patients with locally advanced or metastatic sarcoma treated with talimogene laherparepvec in combination with pembrolizumab: A phase 2 clinical trial Journal Article
| Authors: | Kelly, C. M.; Antonescu, C. R.; Bowler, T.; Munhoz, R.; Chi, P.; Dickson, M. A.; Gounder, M. M.; Keohan, M. L.; Movva, S.; Dholakia, R.; Ahmad, H.; Biniakewitz, M.; Condy, M.; Phelan, H.; Callahan, M.; Wong, P.; Singer, S.; Ariyan, C.; Bartlett, E. K.; Crago, A.; Yoon, S.; Hwang, S.; Erinjeri, J. P.; Qin, L. X.; Tap, W. D.; D'Angelo, S. P. |
| Article Title: | Objective response rate among patients with locally advanced or metastatic sarcoma treated with talimogene laherparepvec in combination with pembrolizumab: A phase 2 clinical trial |
| Abstract: | Importance: Patients with advanced sarcoma have limited treatment options. Talimogene laherparepvec (T-VEC) has been shown to increase tumor-specific immune activation via augmenting antigen presentation and T-cell priming. Objective: To examine whether T-VEC in combination with pembrolizumab is associated with increased tumor-infiltrating lymphocyte infiltration and programmed death-ligand 1 expression and thus with increased antitumor activity in patients with locally advanced or metastatic sarcoma. Design, Setting, and Participants: This open-label, single-institution phase 2 interventional trial of T-VEC plus pembrolizumab enrolled 20 patients with locally advanced or metastatic sarcoma between March 16 and December 4, 2017, for whom at least 1 standard systemic therapy had failed. The median duration of therapy was 16 weeks (range, 7-67 weeks). Reported analyses include data through December 14, 2018. Intervention: Patients received pembrolizumab (200-mg flat dose) intravenously and T-VEC (first dose, ≤4 mL × 106 plaque-forming units [PFU]/mL; second and subsequent doses, ≤4 mL × 108 PFU/mL) injected into palpable tumor site(s) on day 1 of each 21-day cycle. Main Outcomes and Measures: The primary end point was objective response rate (ORR; complete response and partial response) at 24 weeks determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1, criteria. Secondary end points included best ORR by immune-related RECIST criteria, progression-free survival rate at 24 weeks, overall survival, and safety. Results: All 20 patients (12 women [60%]; median age, 63.5 years [range, 24-90 years]) were evaluable for response. The study met its primary end point of evaluating the best ORR at 24 weeks determined by RECIST, version 1.1, criteria; the best ORR was 30% (95% CI, 12%-54%; n = 6). The ORR overall was 35% (95% CI, 15%-59%; n = 7). The incidence of grade 3 treatment-related adverse events was low (4 patients [20%]). There were no grade 4 treatment-related adverse events or treatment-related deaths. Conclusions and Relevance: In this phase 2 clinical trial, treatment with T-VEC plus pembrolizumab was associated with antitumor activity in advanced sarcoma across a range of sarcoma histologic subtypes, with a manageable safety profile. This combination therapy met its predefined primary study end point; further evaluation of T-VEC in combination with pembrolizumab for patients with select sarcoma subtypes is planned. © 2019 American Medical Association. All rights reserved. |
| Keywords: | adult; clinical article; controlled study; protein expression; aged; overall survival; fatigue; advanced cancer; drug safety; drug withdrawal; side effect; treatment duration; outcome assessment; tumor associated leukocyte; progression free survival; phase 2 clinical trial; anemia; thrombocytopenia; cohort analysis; antineoplastic activity; chill; coughing; fever; pneumonia; pruritus; sarcoma; aspartate aminotransferase; drug response; scoring system; nausea and vomiting; open study; hypothyroidism; lymphocytic infiltration; drug substitution; amylase; uveitis; programmed death 1 ligand 1; optic neuritis; talimogene laherparepvec; human; male; female; article; pembrolizumab |
| Journal Title: | JAMA Oncology |
| Volume: | 6 |
| Issue: | 3 |
| ISSN: | 2374-2437 |
| Publisher: | American Medical Association |
| Date Published: | 2020-03-01 |
| Start Page: | 402 |
| End Page: | 408 |
| Language: | English |
| DOI: | 10.1001/jamaoncol.2019.6152 |
| PUBMED: | 31971541 |
| PROVIDER: | scopus |
| PMCID: | PMC6990941 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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