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First-in-human, phase I study of PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in biochemical relapse (BCR) and metastatic castration-resistant prostate cancer (mCRPC).

Publication ,  Conference
Autio, KA; Higano, CS; Nordquist, LT; Appleman, LJ; Zhang, T; Zhu, X; Babiker, HM; Vogelzang, NJ; Prasad, S; Schweizer, MT; Billotte, S; Li, R ...
Published in: Journal of Clinical Oncology
May 20, 2021

2612 Background: Therapeutic vaccines targeting PC-associated antigens represent attractive approaches in combination with immune checkpoint inhibitors (ICI). Safety/antitumor activity of PF-06753512 (PrCa VBIR) was evaluated in a phase I, dose-escalation and expansion study in patients (pts) with BCR prior to ADT and in pts with mCRPC either prior to or after failure of novel hormone therapy. PrCa VBIR consists of: 1) priming immunization with a replication-deficient adenoviral vector (AdC68) expressing PSA, prostate-specific membrane antigen and prostate stem cell antigen; 2) boosts with plasmid DNA (pDNA) encoding the same antigens by IM electroporation; 3) ICI given subcutaneously, including anti CTLA-4 antibody tremelimumab (TRM) and anti PD-1 antibody sasanlimab (SSL). Methods: AdC68 ± ICI(s) were given on months (mos) 1 and 5 and pDNA ± ICI(s) on mos 2–4 and 6–8. After 8 mos, maintenance pDNA + ICI(s) were given every 1 or 2 mos. In Part A (6 escalation cohorts), pts with mCRPC received AdC68 (4 or 6x10e11 viral particles) + pDNA 5 mg ± ICIs (TRM alone 80 mg; TRM 40 or 80 mg + SSL 130 or 300 mg). In Part B (3 expansion cohorts), pts with mCRPC received AdC68 6x10e11 + pDNA 5 mg + TRM 80 mg + SSL 300 mg; pts with BCR received similar vector and pDNA + TRM 80 mg ± SSL 130 mg. Primary objectives: Assess overall safety (CTCAE v4.03), determine expansion dose. Secondary objectives: Anti-tumor activity (RECIST v1.1, Prostate Cancer Working Group 3, PSA 50 response) and immune response. (Note: Database remains open, some queries pending). Results: As of Sept 15, 2020, 91 pts were treated in dose-escalation (n=38) and expansion (n=53; BCR=35, mCRPC=18). Immune responses (ELISpot) were positive in some pts. Grade (G) 3 or 4 treatment-related adverse events (TRAEs) developed in 38.5% (35/91) of pts. G5 TRAEs occurred in 2 pts (n=1 G4 myasthenia gravis + G5 pulmonary embolism; n=1 G5 myocarditis). irAEs were more frequent in BCR compared to mCRPC. See the table for efficacy data. Conclusions: Vaccination with PrCa VBIR had a manageable safety profile. TRAEs increased when 2 ICIs were given. Some pts with BCR experienced durable PSA-50 responses without ADT; patients with mCRPC had few objective tumor responses, but had prolonged median rPFS. PrCa VBIR appears to stimulate antigen-specific immunity and results in noticeable antitumor activity, particularly in androgen sensitive disease. Clinical trial information: NCT02616185. [Table: see text]

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

May 20, 2021

Volume

39

Issue

15_suppl

Start / End Page

2612 / 2612

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
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MLA
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Autio, K. A., Higano, C. S., Nordquist, L. T., Appleman, L. J., Zhang, T., Zhu, X., … Petrylak, D. P. (2021). First-in-human, phase I study of PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in biochemical relapse (BCR) and metastatic castration-resistant prostate cancer (mCRPC). In Journal of Clinical Oncology (Vol. 39, pp. 2612–2612). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2021.39.15_suppl.2612
Autio, Karen A., Celestia S. Higano, Luke T. Nordquist, Leonard Joseph Appleman, Tian Zhang, Xinhua Zhu, Hani M. Babiker, et al. “First-in-human, phase I study of PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in biochemical relapse (BCR) and metastatic castration-resistant prostate cancer (mCRPC).” In Journal of Clinical Oncology, 39:2612–2612. American Society of Clinical Oncology (ASCO), 2021. https://doi.org/10.1200/jco.2021.39.15_suppl.2612.
Autio KA, Higano CS, Nordquist LT, Appleman LJ, Zhang T, Zhu X, et al. First-in-human, phase I study of PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in biochemical relapse (BCR) and metastatic castration-resistant prostate cancer (mCRPC). In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 2612–2612.
Autio, Karen A., et al. “First-in-human, phase I study of PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in biochemical relapse (BCR) and metastatic castration-resistant prostate cancer (mCRPC).Journal of Clinical Oncology, vol. 39, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 2612–2612. Crossref, doi:10.1200/jco.2021.39.15_suppl.2612.
Autio KA, Higano CS, Nordquist LT, Appleman LJ, Zhang T, Zhu X, Babiker HM, Vogelzang NJ, Prasad S, Schweizer MT, Billotte S, Binder J, Cavazos N, Li R, Chan K, Cho H, Dermyer M, Hollingsworth R, Kern KA, Petrylak DP. First-in-human, phase I study of PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in biochemical relapse (BCR) and metastatic castration-resistant prostate cancer (mCRPC). Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. 2612–2612.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

May 20, 2021

Volume

39

Issue

15_suppl

Start / End Page

2612 / 2612

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences