Trial has met primary endpoints of safety and
immunogenicity and secondary endpoint for efficacy based on
response rate
Trial data published today in Nature
Medicine
Selected clinical trial data also presented at
the 2024 AACR Annual Meeting
PHILADELPHIA, April 7, 2024 /PRNewswire/ -- Geneos
Therapeutics, a clinical stage biotherapeutics company focused on
the development of personalized therapeutic cancer vaccines
(PTCVs), today announced the publication of positive safety,
immunogenicity, and efficacy data from the full cohort of patients
enrolled in its GT-30 clinical trial in Nature Medicine.
The paper, titled, "Personalized Neoantigen Vaccine and
Pembrolizumab in Advanced Hepatocellular Carcinoma: A phase 1/2
trial," details the GT-30 clinical trial, a 36-patient,
single-arm, open-label, multi-center Phase 1/2 study of GNOS-PV02,
a DNA plasmid encoded PTCV in combination with DNA plasmid encoded
IL-12 (a cytokine adjuvant), and pembrolizumab (a PD-1 inhibitor)
in second-line (2L) patients with advanced hepatocellular carcinoma
(HCC) previously treated with a multi-tyrosine kinase inhibitor.
The study met its primary endpoints of safety and immunogenicity
and its secondary endpoint of efficacy based on observed response
rate (ORR).
PTCV-related adverse events were all limited to Grades 1 and 2
with no dose-limiting toxicities or grade > 3 adverse events
observed. The most common adverse events were injection site
reactions observed in 41.6% (15/36) of patients. This is in
contrast to typical immuno-oncology combination regimens, including
those approved for first-line use in advanced HCC, wherein adding a
second agent may lead to markedly increased toxicity; here, the
addition of a PTCV to a PD-1 inhibitor was not observed to lead to
any significant decrease in patient safety and tolerability.
The ORR for GT-30 is currently at 30.6% (11/36), including three
complete responses (CR) and eight partial responses. This response
is statistically significant based on pre-specified criteria at a
one-sided p-value = 0.031 (1-sided 90% CI 20.4%-100%) versus a
pre-specified historical control of 16.9% for pembrolizumab
monotherapy. This historical comparator response rate was modeled
on Phase 3 KN-240 data presented at ASCO 2019 and is also
consistent with the prior Phase 2 KN-224 study. As an overall
class, anti-PD1 monotherapy for 2L advanced HCC has shown response
rates of 11%-18% in seven Phase 2 and Phase 3 clinical studies
enrolling over 1400 patients. Additionally, the GT-30 CR rate of
8.3% (3/36) compares with a historical anti-PD-1 monotherapy CR
rate in 2L of 0% - 3% in the prior studies. As of the data cutoff,
the median OS (mOS) in GT-30 was 19.9 months compared to a mOS
range of 12.9 – 15.1 months reported for the prior 2L studies of
pembrolizumab and other anti-PD-1 monotherapy. 11 of 36 patients
remain on treatment and, in total, 17 patients continue to be
followed for overall survival (OS).
"Other recent industry trials have tested personalized cancer
vaccines in patients with highly immune-sensitive tumor phenotypes
and no measurable disease. In marked contrast, the GT-30 trial
assesses PTCVs in HCC, a cancer with very low tumor mutational
burden and an immune-excluded phenotype, and in patients with
significant late-stage unresectable and metastatic disease," said
Niranjan Sardesai, PhD, CEO and
president of Geneos. "Despite the small size of this study, our
results are important for the advancement of the field. We have not
only met endpoints for safety, immunogenicity, and clinical
efficacy based on ORR in this difficult to treat setting, but our
mechanism of action data trace and confirm every step, from
vaccination to tumor reduction, required to explain the
immunological basis for the observed clinical responses."
Immunological analyses confirm the induction of new T cell
responses to vaccine-encoded neoantigens in 14 of 14 (100%)
evaluated patients and the expansion of this TCR repertoire both in
the peripheral blood and tumors of PTCV-treated patients. Single
cell sequencing analyses show the vast majority of these T cell
clones to be CD8 T effector memory cells, a key requirement to
induce anti-tumor cytotoxicity. In contrast, while anti-PD-1
monotherapy has been observed to reverse T cell dysfunction in
existing neoantigen-specific T cell clones, it is not known to
induce any new neoantigen-specific T cell clones.
Today Geneos also presented selected GT-30 clinical trial data
and updated longitudinal circulating tumor DNA (ctDNA) biomarker
data from the trial at the 2024 American Association for Cancer
Research (AACR) Annual Meeting in San
Diego. Reductions of at least 50% versus baseline in patient
ctDNA, an exploratory endpoint, were seen in 40.7% of patients (11
of 27 patients for whom the full data set are available). All such
responses correlate with ongoing survival.
"To our knowledge, the GT-30 clinical study provides the first
definitive demonstration of a personalized cancer vaccine enhancing
clinical response to anti-PD-1 therapy by inducing new,
neoantigen-specific T cells which traffic to the tumor," said
Ildiko Csiki, MD, PhD, chief
medical officer of Geneos. "The fact that the PTCV regimen has
produced this important result in a form of cancer as
immunologically 'cold' as HCC, leading to multiple complete
responses and a doubling of objective response versus PD-1, is
incredibly promising and shows the therapeutic potential of
personalized cancer vaccines for cancer patients."
DNA-based PTCVs may include up to 40 neoantigens. The majority
of patients in the GT-30 study were administered PTCVs which
included all of their targetable neoantigens across a broad range
of predicted MHC binding affinity. A correlation was seen in GT-30
between the number of vaccine epitopes and the number of reactive
epitopes post-vaccination, suggesting that having more neoantigens
in the vaccine increased the effectiveness of tumor control. Other
personalized vaccine platforms, especially those not based on DNA,
have historically had to target a more limited selection of
neoantigens, which may limit their efficacy.
About Geneos Therapeutics
Geneos Therapeutics, a clinical stage biotherapeutics company, is
developing personalized therapeutic cancer vaccines (PTCVs) that
may serve an important role in new immunotherapeutic paradigms for
cancer. The company's approach, using its proprietary GT-EPIC™
platform, is to target neoantigens (abnormal mutations produced by
cancer cells) from individual patient tumors to develop novel and
uniquely personalized treatments for cancer. Planning is underway
for a potentially registrational clinical trial in advanced
hepatocellular carcinoma. For more information, please
visit www.geneostx.com.
This press release contains certain forward-looking
statements relating to our business, including our plans regarding
the development of personalized therapeutic cancer vaccines and the
therapeutic potential and clinical benefits of our product
candidates. Actual events or results may differ from the
expectations set forth herein. There can be no assurance that any
product candidate in Geneos' pipeline will be successfully
developed, manufactured or commercialized, that final results of
clinical trials will be supportive of regulatory approvals required
to market licensed products, or that any of the forward-looking
information provided herein will be proven accurate.
Forward-looking statements speak only as of the date of this
release, and Geneos undertakes no obligation to update or revise
these statements, except as may be required by law.
This press release does not constitute an offer to sell or
the solicitation of an offer to buy any securities.
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SOURCE Geneos Therapeutics, Inc.