TY - JOUR
T1 - Phase II Trial of MEDI0457 and Durvalumab for Patients With Recurrent/Metastatic Human Papillomavirus-Associated Cancers
AU - Morris, Van K.
AU - Jazaeri, Amir
AU - Westin, Shannon N.
AU - Pettaway, Curtis
AU - George, Solly
AU - Huey, Ryan W.
AU - Grinsfelder, Michaela
AU - Shafer, Aaron
AU - Johnson, Benny
AU - Vining, David
AU - Guo, Ming
AU - Fellman, Bryan
AU - Frumovitz, Michael
N1 - Funding Information:
V.K.M. was supported by the NIH/NCI under award number K12 CA088084 and the Cancer Prevention & Research Institute of Texas (CPRIT) under award number RP220416. This study was supported by the HPV Moonshot Program at MD Anderson and the NIH CCSG Award CA016672 (Institutional Tissue Bank [ITB] and Research Histology Core Laboratory [RHCL]), Adaptive Patient-Oriented Longitudinal Learning and Optimization (APOLLO) Moonshot Program, Strategic Alliances and the Translational Molecular Pathology-Immunoprofiling lab (TMP-IL) at the Department Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center. AstraZeneca provided the study drug and provided funding to MD Anderson Cancer Center for study conduct.
Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press.
PY - 2023/7
Y1 - 2023/7
N2 - Background: Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers. Methods: Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg intravenously every 4 weeks. The primary endpoint was overall response (RECIST 1.1). In this Simon two-stage phase 2 trial (Ho: p<0.15; Ha: p≥0.35), ≥2 responses were needed in both cervical and non-cervical cohorts during the first stage for the trial to proceed to stage 2 with an additional 25 patients (34 total) enrolled. Results: Twenty-one patients (12 cervical, 7 anal, and 2 penile) were evaluable for toxicity and 19 for response Overall response rate was 21% (95% CI, 6%-46%) among evaluable patients. Disease control rate was 37% (95% CI, 16%-62%). Median duration of response among responders was 21.8 months (95% CI, 9.7%-not estimable). Median progression-free survival was 4.6 months (95% CI, 2.8%-7.2%). Median overall survival was 17.7 months (95% CI, 7.6%-not estimable). Grades 3-4 treatment-related adverse events occurred in 6 (23%) participants. Conclusions: The combination of MEDI0457 and durvalumab demonstrated acceptable safety and tolerability in patients with advanced HPV-16/18 cancers. The low ORR among patients with cervical cancer led to study discontinuation despite a clinically meaningful disease control rate.
AB - Background: Human papillomavirus (HPV) types 16/18 drive oncogenesis for most patients with cervical, anal, and penile cancers. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 HPV-16/18 viral oncogenes and IL-12 adjuvant, is safe and provokes an immune response against E6/E7. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for patients with HPV-associated cancers. Methods: Patients with recurrent/metastatic, treatment-refractory HPV-16/18 cervical cancer, or rare HPV-associated (anal and penile) cancers were eligible. Prior immune checkpoint inhibition was not permitted. Patients received MEDI0457 7 mg intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg intravenously every 4 weeks. The primary endpoint was overall response (RECIST 1.1). In this Simon two-stage phase 2 trial (Ho: p<0.15; Ha: p≥0.35), ≥2 responses were needed in both cervical and non-cervical cohorts during the first stage for the trial to proceed to stage 2 with an additional 25 patients (34 total) enrolled. Results: Twenty-one patients (12 cervical, 7 anal, and 2 penile) were evaluable for toxicity and 19 for response Overall response rate was 21% (95% CI, 6%-46%) among evaluable patients. Disease control rate was 37% (95% CI, 16%-62%). Median duration of response among responders was 21.8 months (95% CI, 9.7%-not estimable). Median progression-free survival was 4.6 months (95% CI, 2.8%-7.2%). Median overall survival was 17.7 months (95% CI, 7.6%-not estimable). Grades 3-4 treatment-related adverse events occurred in 6 (23%) participants. Conclusions: The combination of MEDI0457 and durvalumab demonstrated acceptable safety and tolerability in patients with advanced HPV-16/18 cancers. The low ORR among patients with cervical cancer led to study discontinuation despite a clinically meaningful disease control rate.
KW - anti-PD-L1
KW - DNA vaccine
KW - HPV
KW - immunotherapy
KW - metastasis
UR - http://www.scopus.com/inward/record.url?scp=85164243676&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85164243676&partnerID=8YFLogxK
U2 - 10.1093/oncolo/oyad085
DO - 10.1093/oncolo/oyad085
M3 - Article
C2 - 37104874
AN - SCOPUS:85164243676
SN - 1083-7159
VL - 28
SP - 618
EP - 623
JO - Oncologist
JF - Oncologist
IS - 7
ER -