PIC Monotherapy Shows Long-Term Promise in Patients with Glioblastoma and HCC

Two patients with aggressive cancers reached 5 and 6 years, respectively, of durable recurrence-free survival (RFS) while receiving personalized DNA-based tumor-infiltrating lymphocyte (TIL)-inducing therapies, according to Geneos Therapeutics, manufacturer of the treatment.¹

One patient has glioblastoma multiforme (GBM), and the other patient has advanced hepatocellular carcinoma (HCC) treated in the second line. Neither patient has experienced PIC-related adverse events (AEs) greater than grade 1 or treatment-related serious AEs.

The therapy, known as personalized immunotherapy for cancer (PIC), is a neoantigen-based personalized DNA vaccine being assessed for the treatment of HCC, GBM, and anaplastic astrocytoma.²

“Durable overall survival [OS] of [5] years or more in GBM and advanced HCC are uncommon, while recurrence-free survival is almost unheard of,” said Ildiko Csiki, MD, PhD, chief medical officer of Geneos, in a press release. “If confirmed in larger datasets, we expect these results to align with FDA’s guidance on overall survival as a primary end point for registrational studies.”

The patient with GBM received standard-of-care treatment of surgery, radiation, and temozolomide in addition to a single dose each of 2 experimental treatments. The patient began PIC monotherapy 1 year after diagnosis. In this setting, the median RFS is 26 months and OS is 40 months, with a 5-year survival rate less than 10%.¹ The patient is now at 75 months of RFS and 87 months from surgical resection.

The patient with HCC presented with a beta-catenin–mutated form of HCC, which progressed despite liver resection and oncolytic virus and sorafenib (Nexavar) treatment. After 2 years of a combination of PIC and pembrolizumab (Keytruda) treatment in Geneos’ GT-30 phase 1b/2a trial (NCT04251117),³ the patient switched to PIC monotherapy.

The median OS for patients with HCC treated with averages to 14 months with 3 to 4 months of progression-free survival.¹ The patient treated with PIC has now reached 60 months of RFS.

“Geneos’ PICs as monotherapy have now enabled patients with two distinct, difficult-to-treat, rapidly progressing cancers to live beyond five years, recurrence free and healthy – living rich, fulfilling lives,” added Niranjan Sardesai, PhD and president and CEO of Geneos, in the press release. “These cases, together with our broader clinical trial results, highlight the durability and tolerability we believe to be achievable with our DNA-based PIC therapy. These results are encouraging, and we look forward to continuing to advance our clinical program so that we may bring this potential new treatment option to people living with aggressive cancers rapidly.”

Geneos plans on continuing the advancement and study of PIC monotherapy in the upcoming GT-31 phase 2b randomized, controlled clinical trial in patients with HCC.¹

TIL therapy has emerged as a promising adoptive cell transfer strategy for solid tumors. The FDA approved lifileucel (Amtagvi) for patients with advanced melanoma who have progressed following anti–PD-(L1) inhibitor therapy in February 2024, marking it as the first cellular therapy in solid tumors.⁴

REFERENCES:

1. Patients With Aggressive Brain and Advanced Liver Cancers Treated with Geneos’ Personalized Immunotherapy for Cancer as Monotherapy Reach Five Years of Durable Recurrence-Free Survival. News release. Geneos Therapeutics. September 18, 2025. Accessed October 1, 2025. https://tinyurl.com/5ddyjp27

2. Our Approach. Geneos Therapeutics. Accessed October 1, 2025. https://www.geneostx.com/gt-epic-platform/

3. GNOS-PV02 Personalized Neoantigen Vaccine, INO-9012 and Pembrolizumab in Subjects with Advanced HCC. ClinicalTrials.gov. Updated January 31, 2025. Accessed October 1, 2025. https://clinicaltrials.gov/study/NCT04251117

4. FDA approves first cellular therapy to treat patients with unresectable or metastatic melanoma. News release. FDA. February 16, 2024. Accessed February 16, 2024. http://tinyurl.com/5n7cuszk