IGV-001 Showcases Positive Benefit-Risk Profile in Newly Diagnosed Glioblastoma

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IGV-001, an autologous cell immunotherapy, did not show emerging risks or a change to its benefit-risk profile compared with placebo in patients with newly diagnosed glioblastoma (GBM), according to blinded early-safety data from a phase 2b trial (NCT04485949) that were presented during the 2024 Society for Neuro-Oncology Annual Meeting.¹

A total of 86 serious adverse effects (SAEs) were reported, including 85 treatment-emergent (TE) SAEs and 1 non-TESAE, the latter of which was seen in a patient who failed screening. SAEs occurred most frequently in System Organ Class nervous system disorders (37.9%), general disorders and administration site conditions (7.4%), and the infections and infestations System Organ Class (7.4%).

Serious AEs that occurred in at least 2 patients from these 3 System Organ Class categories included seizure (15.8%), disease progression (5.3%), headache (4.2%), and pulmonary embolism (4.2%).

Additionally, 16 deaths were reported in the safety population (16.8%) irrespective of causality. There were 2 deaths in patients who were within 50 years of age and 14 had occurred in those older than 50 years; 9 of the deaths overall occurred in men. Two deaths were due to SAEs, which were specific to sepsis and hypotension, both of which were unrelated to the blinded study product.

“Available data show that the nature, the severity, and the frequency of reported adverse events are strongly indicative of causal relationships to the standard of care and the patients’ preexisting medical conditions and their natural complications,” lead study author J. Bradley Elder, MD, director of Neurosurgical Oncology and professor in the Department of Neurological Surgery at the Brain and Spine Tumor Center, The Ohio State University Wexner Medical Center in Columbus, said in an oral presentation during the meeting.

IGV-001 has the ability to induce cellular stresses on GBM cells, which thereby results in immunogenic cell death and consequent antitumor activity. Additionally, dying or dead tumor cell antigens, IMV-001, and damage-associated molecular patterns immune stimulators (DAMPs) also diffuse from biodiffusion chambers into surrounding tissue and combine with local DAMPs at the implantation site. This trains the immune system to create tumor-specific T-cell responses that reduce or eliminate tumor burden.

Elder explained that IGV-00, which is under the Imvax Goldspire platform, has a full antigenic signature capture, broad spectrum immune activation, overnight tissue progressing, and has been integrated into standard-of-care (SOC) regimens. It does not have off-target effects, he added.

As part of the process with IGV-001, patients undergo tumor excision followed by tumor cells and antisense oligonucleotide and incubation. Biodiffusion chambers are filled and irradiated, and treatment gets implanted once for 48 hours and is then explanted from the abdomen. Manufacturing is completed in less than 1 day.

Prior phase 1b (NCT02507583) results showed that IGV-001 was found to be well tolerated with an exposure-response relationship; data also demonstrated favorable progression-free survival (PFS) and overall survival (OS) outcomes vs historical SOC data, which was 6.5 months and 16.2 months, respectively.^2-4

In the phase 1b trial, the median PFS and OS in the intention-to-treat population (n = 33) was 9.8 months and 17.3 months, respectively, and was 10.4 months and 21.9 months, respectively, in the highest exposure group (n = 17).5 In those who met Stupp-eligible criteria and were in highest exposure group, the median PFS was 17.1 months and the median OS was 38.2 months. The 2-year OS rate in the highest exposure group was 44% (n = 17).

As a next step, investigators sought to compare a one-time treatment of IGV-001 plus standard radiation and temozolomide with placebo plus standard therapy.

In the multicenter, double-blind, randomized phase 2b trial, patients with newly diagnosed GBM aged 18 to 70 years, underwent screening with MRI on day –14 through day –3, with a screening/randomization period with craniotomy followed by a 2:1 randomization on day –2 through day 0. Abdominal incisions were performed following randomizations. Treatment was administered on days 1 through 28 (implant on day 1, explant on day 3, and postoperative visits on days 14 and 28), with standard treatment comprised of radiation and temozolomide given weeks 7 to 12 followed by temozolomide on weeks 17 through 41. Patients were then followed through months 10 to 36.

Sixty-six patients were randomized to IGV-001 compared with 33 who were on the placebo arm. In total, 94 patients (94.9%) were implanted with biodiffusion chambers and had enough follow-up time to begin treatment with concurrent radiation and temozolomide, and 84 patients (89.4%) had enough follow-up time who began treatment with concurrent radiation and temozolomide. A total 36 patients (37.9%) and 14 patients (14.7%) discontinued treatment and the study, respectively.

The primary end point is PFS, with OS as a secondary end point. Elder noted that the study fully enrolled in 13 months, encompassing patients across 20 sites in the United States. The safety period data cutoff date was July 14, 2024.

Baseline characteristics reported encompassed all patients in the safety population (n = 95). The median age was 60.0 years (range, 24-70), with most patients being between the ages of 51-70 years (70.5%). More than half of patients were White (85.3%) and male (63.2%).

Elder added that patients who were aged 51 to 70 years appeared to be more likely to experience SAEs, which suggest a potential impact of age-related predisposing comorbidity factors.

Investigators are planning to present PFS data in the middle of 2025, followed by an OS data presentation in mid-2026. Outcomes from 2 Independent Data Monitoring Committee (IDMC) meetings included recommendations that the study should continue as planned. A final IDMC meeting is scheduled to take place in December 2024.

Editor’s Note: Dr Elder did not cite any disclosures in his presentation.

References

1. Elder JB, Hanft S, Lee IY, et al. Early safety data from a randomized, multicenter, double-blind, phase 2b study of IGV-001, an autologous cell immunotherapy, versus placebo, in newly diagnosed glioblastoma (ndGBM). Presented at: 2024 SNO Annual Meeting; November 21-24, 2024; Houston, TX. Abstract CTIM-14.
2. Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy–temozolomide for newly diagnosed glioblastoma. N Eng J Med. 2014;370(8):709-722. doi:10.1056/NEJMoa1308345
3. Gilbert MR, Dignam JJ, Armstrong TS, et al. A randomized trial of bevacizumab for newly diagnosed glioblastoma. N Engl J Med. 2014;370(8):699-708. doi:10.1056/NEJMoa1308573
4. Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009;10(5):459-466. doi:10.1016/S1470-2045(09)70025-7
5. Andrews DW, Judy KD, Scott CB, et al. Phase Ib clinical trial of IGV-001 for patients with newly diagnosed glioblastoma. Clin Cancer Res. 2021;27(7):1912-1922. doi:10.1158/1078-0432.CCR-20-3805