On May 29, 2020 Ziopharm Oncology, Inc. (Nasdaq: ZIOP), reported the presentation of final clinical data from its phase 1 monotherapy ("Main") study of Controlled IL-12, Ad-RTS-hIL-12 plus veledimex (Ad+V), as well as updated clinical data from two phase 1 substudies of Ad+V, a monotherapy expansion study ("Expansion") and a combination study with a PD-1 inhibitor, for the treatment of adult recurrent or progressive glioblastoma multiforme (rGBM) at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual (Virtual) Meeting (Press release, Ziopharm, MAY 29, 2020, View Source [SID1234558685]).

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"The results we have seen from the two Controlled IL-12 monotherapy studies are particularly promising, with median overall survival in unifocal patients after monotherapy Ad+V treatment remaining at 16.2 months after longer term follow-up, as well as encouraging preliminary data from the PD-1 combination study where median overall survival has not yet been reached," said Dr. Antonio Chiocca, M.D., Ph.D., Trial Investigator and Professor of Neurosurgery at Harvard Medical School, Surgical Director of the Center for Neuro-Oncology at Dana-Farber Cancer Institute, and Chairman of Neurosurgery and Co-Director of the Institute for the Neurosciences at Brigham and Women’s Hospital. "We also reported three additional partial responses, one in the monotherapy Main study, one in the Expansion study and one in the combination study, bringing the total number of partial responses (PRs) to five. Observing responses in brain tumors in the setting of recurrence is unusual and highly encouraging, and, along with the survival data, highlight the potential of Ad+V for the treatment of rGBM."

Laurence Cooper, M.D., Ph.D., Chief Executive Officer of Ziopharm, added, "According to most recent data, even with the best available therapies, median overall survival for unifocal rGBM patients appears to be 6-12 months. We are therefore heartened by the collection of data presented at ASCO (Free ASCO Whitepaper) across our three studies, which demonstrate survival benefits beyond a year supported by imaging studies showing tumor regression and biopsies revealing that Ad+V administration turns ‘cold’ tumors ‘hot’ by recruiting T cells into the tumor. We look forward to continuing to report follow-up monotherapy and combination phase 1 data, as well as initial data from the ongoing phase 2 study of Ad+V in combination with Libtayo, which is nearing completion of enrollment."

Ad-RTS-hIL-12 plus 20 mg/day veledimex is currently being examined in a phase 1 monotherapy "Expansion" substudy for the treatment of rGBM (NCT03679754) that enlarged the phase 1 "Main" veledimex dose escalation trial (NCT02026271) by an additional 36 patients. New clinical results in monotherapy were shared in poster presentations.

Final data highlights from the "Main" dose escalation monotherapy study, titled "Final results of Controlled IL-12 Monotherapy in Adults with Grade III or IV Gliomas," (Abstract #3040) include:

Subjects (n=6, unifocal, craniotomy) who received low-dose (≤ 20 mg cumulative) corticosteroids during veledimex dosing (Days 0 to 14, coinciding with administration of veledimex) had a median overall survival (mOS) of 17.8 months (mean follow-up of 18.4 months)
15 subjects (n=14, unifocal, craniotomy) treated with Ad (Day 0) and 20 mg veledimex with any dosing of corticosteroids had a mOS of 12.7 months (mean follow-up of 13.1 months)
Serial MRIs show patient with confirmed PR at 72 weeks, with durability at 96 weeks and monitoring ongoing
Veledimex-dependent and proportional increases in IL-12 and IFN-γ, resulting in immune activation
Favorable safety profile:
Ad+V was safely administered and tolerable in both craniotomy (Group 1, n=31) and stereotactic subjects (Group 2, n=7)
52 serious adverse event (SAEs) were reported in 21 subjects (55%) and 14 related SAEs were reported in 12 subjects (32%). There have been no study treatment related deaths
The 20 mg veledimex dose is the recommended phase 2 dose as confirmed in the "Expansion" substudy focusing on veledimex 20 mg (n=36; ASCO (Free ASCO Whitepaper) 2020 #2564)
The 10 mg veledimex dose level was studied to move forward as the starting dose in the monotherapy study for pediatric subjects (NCT03330197) and in combination therapy with PD-1 inhibitor in adults with rGBM (ASCO 2020 #2510)
Data highlights from the "Expansion" study, titled "Survival of Subjects with Recurrent Glioblastoma Receiving Intratumoral Administration of Controlled IL-12 with Limited Exposure to Dexamethasone," (Abstract #2564) include:

Subjects receiving Ad (Day 0, craniotomy) and 20 mg (Days 0 to 14) veledimex with unifocal disease ("Main" and "Expansion" n=20) administered low-dose corticosteroids showed mOS of 16.2 months (mean follow-up of 14.1 months)
Serial MRIs show patient with previously reported pseudoprogression now has confirmed PR at 30 weeks and response durability out to 48 weeks (follow-up ongoing), in addition to the PR previously reported 1
Adverse reactions remained consistent with previously reported results, being predictable and promptly reversible upon discontinuation of veledimex, and there were no drug-related deaths
Veledimex dosing compliance was comparable to and slightly higher than the "Main" study
Combination of Ad+V with the PD-1 inhibitor nivolumab (nivo) is being examined in a phase 1 substudy for the treatment of rGBM (NCT03636477). Data highlights shared in a poster discussion titled "Controlled IL-12 in Combination with a PD-1 Inhibitor: Subjects with Recurrent Glioblastoma" (Abstract #2510) include:

mOS has not been reached, with mean follow-up at 8.3 months
Drug-related toxicities were comparable to monotherapy, being predictable, dose-related, and promptly reversible upon discontinuation of veledimex
As previously reported from Ad+V monotherapy, plasma pharmacokinetics (PK) demonstrates an exposure-response relationship for veledimex
Serum IL-12 was detected in all subjects following initiation of Ad+V, typically followed by a transient increase in downstream serum IFN-γ, which is consistent with previously reported data of Ad+V monotherapy
There is evidence of immune-mediated anti-tumor effects, with serial MRIs showing pseudoprogression and one new PR, in addition to the PR previously reported2
To further investigate Ad+V in combination with an immune checkpoint inhibitor in rGBM subjects, a phase 2 trial of Ad+V in combination with cemiplimab-rwlc (Libtayo) is currently ongoing (NCT04006119).

More information about Controlled IL-12 is available on the Company’s website at View Source Additionally, the posters presented at the ASCO (Free ASCO Whitepaper) 2020 Virtual Meeting will be available on the Company’s website in the "Scientific and Medical Publications" section.