Skip to main content

LUMINOS-101: Phase 2 study of PVSRIPO with pembrolizumab in recurrent glioblastoma.

Publication ,  Conference
Sloan, AE; Buerki, RA; Murphy, C; Kelly, AT; Ambady, P; Brown, M; Butowski, NA; Cavaliere, R; Curry, WT; Desjardins, A; Franklin, L; Mixson, L ...
Published in: Journal of Clinical Oncology
May 20, 2021

TPS2065 Background: The prognosis for patients (pts) with recurrent (r) glioblastoma (GBM) is poor, with no highly effective approved therapies. Treatment failure may result from poor penetration of drugs through the blood-brain barrier and the immunosuppressive nature of the tumor microenvironment (TME). PVSRIPO, a recombinant poliovirus (PV):rhinovirus chimera, is a novel, non-neurovirulent, intratumoral immunotherapy. Trial results in rGBM pts show greater long-term survival with PVSRIPO monotherapy (21%, 36-60 months [mos]) vs criteria-matched external controls (4%, 36 mos; 2%, 60 mos; Desjardins 2018 NEJM). PVSRIPO targets CD155 (PV receptor), expressed on solid tumors and on APC. PVSRIPO infection results in inflammatory-mediated destruction of tumor cells but non-lethal lingering infection in TME APC. This leads to type I/III interferon-dominant inflammation and, ultimately, tumor antigen-specific T cell activation and recruitment (Brown 2017 Sci Transl Med), which is potentiated by immunologic recall to intratumoral replicating virus via prior vaccination. Induction of type 1 IFN dominant inflammation and compensatory activation of the PD-1:PD-L1 immune checkpoint (IC) pathway support investigation of PVSRIPO in combination with PD-1/L1 IC inhibitors. Immunologically cold mouse glioma models show PVSRIPO+anti-PD-1 therapy resulted in greater anti-tumor response than either agent. Methods: LUMINOS-101 is a phase 2, multicenter, open-label, single-arm study of intratumoral infusion of PVSRIPO (Day 1: 5x10 TCID) followed by the anti-PD-1 monoclonal antibody pembrolizumab (200mg IV q3w) in adult pts with rGBM. The trial objective is to evaluate anti-tumor activity and safety and tolerability of the combination. Eligibility criteria include pts ≥18 years who had prior PV and boost IPOL immunizations, histologically confirmed supratentorial rGBM, infusible 1 to ≤5.5cm enhancing disease, confirmed disease progression following prior therapies, and KPS ≥70. Key exclusion criteria include multifocal disease; discontinuation of prior anti-PD-1/L1 agent for toxicity; prior intratumoral therapy, immunotherapy, or radiotherapy within 12 weeks; high-dose systemic corticosteroids; chemotherapy, anti-VEGF, or TTF therapy ≤1-6 weeks depending on the therapy; serious cerebral herniation syndrome; extensive leptomeningeal, subependymal, or ≥1cm enhancing disease crossing the midline; and severe active comorbidities. Primary endpoints are objective response rate, duration of response, and safety. Secondary endpoints include overall and progression-free survival and disease control rate and duration. Exploratory endpoints include assessment of tumor and blood for biomarkers of response. The initially planned safety lead-in period is now fully enrolled. Recruitment is ongoing in the US, and results will inform the design of a randomized phase 3 trial. Clinical trial information: NCT04479241.

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

TPS2065 / TPS2065

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
Chicago
ICMJE
MLA
NLM
Sloan, A. E., Buerki, R. A., Murphy, C., Kelly, A. T., Ambady, P., Brown, M., … Nichols, G. (2021). LUMINOS-101: Phase 2 study of PVSRIPO with pembrolizumab in recurrent glioblastoma. In Journal of Clinical Oncology (Vol. 39, pp. TPS2065–TPS2065). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2021.39.15_suppl.tps2065
Sloan, Andrew E., Robin Arthur Buerki, Christopher Murphy, Andrea True Kelly, Prakash Ambady, Michael Brown, Nicholas A. Butowski, et al. “LUMINOS-101: Phase 2 study of PVSRIPO with pembrolizumab in recurrent glioblastoma.” In Journal of Clinical Oncology, 39:TPS2065–TPS2065. American Society of Clinical Oncology (ASCO), 2021. https://doi.org/10.1200/jco.2021.39.15_suppl.tps2065.
Sloan AE, Buerki RA, Murphy C, Kelly AT, Ambady P, Brown M, et al. LUMINOS-101: Phase 2 study of PVSRIPO with pembrolizumab in recurrent glioblastoma. In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. TPS2065–TPS2065.
Sloan, Andrew E., et al. “LUMINOS-101: Phase 2 study of PVSRIPO with pembrolizumab in recurrent glioblastoma.Journal of Clinical Oncology, vol. 39, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. TPS2065–TPS2065. Crossref, doi:10.1200/jco.2021.39.15_suppl.tps2065.
Sloan AE, Buerki RA, Murphy C, Kelly AT, Ambady P, Brown M, Butowski NA, Cavaliere R, Curry WT, Desjardins A, Franklin L, Friedman HS, Gromeier M, Jackson L, Mixson L, Ong SS, Randazzo D, Wen PY, Nichols G. LUMINOS-101: Phase 2 study of PVSRIPO with pembrolizumab in recurrent glioblastoma. Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. TPS2065–TPS2065.

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

TPS2065 / TPS2065

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

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