Personalized Neoantigen Vaccine Induces Continued Responses in Pretreated, Advanced HCC

Intradermal injection with GNOS-PV02 plus plasmid-encoded interleukin-12 (PTCV) followed by electroporation elicited complete molecular response (CMR) detected via circulating tumor DNA (ctDNA) in 4 additional patients as second-line therapy in patients with advanced hepatocellular carcinoma (HCC), according to updated data from the open-label, multi-arm phase 1b/2a GT-30 study (NCT04251117).^1,2

Three of the 4 patients achieved a durable partial response (PR) per RECIST v1.1 criteria; the fourth patient experienced lasting stable disease (SD). Under modified RECIST criteria, 3 patients experienced CR and 1 patient experienced PR.

Notably, reductions in ctDNA level occurred prior to improvement by MRI in all patients who achieved CR or PR who also had available ctDNA data.

“As hepatologists and oncologists treating patients with HCC, we're increasingly using ctDNA to monitor tumor response to therapy. In this study, the ctDNA improvements all preceded the MRI improvements, which shows ctDNA’s prognostic importance, especially since HCC lesions sometimes never fully resolve on MRI despite patients having no clinical evidence of residual viable cancer,” Ed Gane, MBChB, MD, FRACP, MNZM, professor of medicine at the University of Auckland, New Zealand, hepatologist and deputy director of the New Zealand Liver Unit at Auckland City Hospital, said in a news release.

“Historically, CRs in advanced HCC from checkpoint inhibitor treatment alone are virtually unheard of. The numerous CRs and CMRs seen here are remarkable and emphasize the role Geneos’ vaccines may have to treat seriously ill patients with late-stage HCC. I’m excited for what these vaccines may mean for these patients, who may now be able to hope, realistically, for a CR to treatment,” Gane added.

The study is evaluating the safety, immunogenicity, and efficacy of PTCV plus pembrolizumab (Keytruda) in 36 patients with unresectable or metastatic Barcelona Clinic Liver Cancer stage B or C HCC not amenable to locoregional therapy or curative-intent therapy with disease progression or intolerance following frontline treatment with sorafenib (Nexavar) or lenvatinib (Lenvima). Notably, PTCV is DNA-based rather than mRNA-, viral-, or peptide-based, allowing up to 40 neoantigens to be housed in each vaccine and up to 80 neoantigens when combining two DNA plasmids.³ Additionally, current manufacturing falls within 6 to 8 weeks and may soon be reduced to 3 to 4 weeks.¹

Previously reported findings from the trial indicated that 3 patients had achieved CR, and a fourth patient had become cancer free, enabling complete resection and treatment with radiation.³

As of the news release, best responses among the 32 evaluable patients included CR (n = 3), PR (n = 7), SD (n = 9), and progressive disease (n = 13).¹

Eleven patients achieved CR, PR, or CMR regardless of whether RECIST v1.1 criteria or ctDNA was used to evaluate response.

Regarding safety, no vaccination-related serious adverse effects have occurred. Vaccination-related AEs, predominantly injection site reactions, have been mild (grade 1/2) and recoverable.

“While we welcome the advances currently observed with mRNA-based cancer vaccines, they are being deployed almost exclusively in the adjuvant setting to prevent cancer recurrence in patients who have had surgery to remove their tumor. As a result, some are even suggesting that personalized therapeutic vaccines may only be effective in the adjuvant setting and ineffective at reducing advanced, unresectable, and metastatic tumors,” Niranjan Sardesai, PhD, president and chief executive officer of Geneos, said.

“We feel these latest data should set the record straight. Cancer vaccines based on our DNA vaccine platform are showing complete responses in patients with late-stage, advanced cancer. We look forward to continuing to develop in the advanced setting with the goal to offer this profoundly important treatment option to patients with advanced cancer, one with a side effect profile, as seen to date, as benign as that for the typical seasonal flu shot.”

References

1. Geneos Therapeutics announces eight of 34 patients to achieve complete response, complete molecular response, or, secondary resectability in ongoing clinical trial of personalized therapeutic cancer vaccination in second line advanced liver cancer. News release. Geneos Therapeutics. August 22, 2023. Accessed August 22, 2023. https://www.geneostx.com/geneos-therapeutics-announces-eight-of-34-patients-to-achieve-complete-response-complete-molecular-response-or-secondary-resectability-in-ongoing-clinical-trial-of-personalized-therapeutic-cancer-v/
2. GNOS-PV02 personalized neoantigen vaccine, INO-9012 and pembrolizumab in subjects with advanced HCC. ClinicalTrials.gov. Updated June 15, 2023. Accessed August 22, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04251117
3. Geneos Therapeutics announces another complete response in ongoing clinical trial of personalized therapeutic cancer vaccination in second line advanced liver cancer. News release. Geneos Therapeutics. December 14, 2022. Accessed August 22, 2023. https://www.geneostx.com/geneos-therapeutics-announces-another-complete-response-in-ongoing-clinical-trial-of-personalized-therapeutic-cancer-vaccination-in-second-line-advanced-liver-cancer/