Tizona Therapeutics, Inc., a privately held, clinical-stage company
developing cancer immunotherapies, today announced first-in-human
Phase 1b clinical data of TTX-080, a novel, first-in-class,
antibody targeting HLA-G, in patients with metastatic colorectal
cancer (mCRC) and locally advanced/metastatic head and neck
squamous cell carcinoma (mHNSCC). The preliminary data will be
presented during a poster session on June 1, 2024, at the American
Society of Clinical Oncology (ASCO) Annual Meeting 2024 in Chicago,
IL.
“Metastatic colorectal cancer is a global health issue,
affecting men and women equally and with rising incidence among
young adults. Despite treatment advances in the last 25 years,
more therapeutic options are needed for those with good performance
status, but whose disease has become unresponsive to available
therapies. Additionally, the prognosis for patients with metastatic
head and neck squamous cell carcinoma is generally poor, also
requiring new treatment approaches to treat this disease,” said OU
Health Stephenson Cancer Center hematologist/oncologist Susanna V.
Ulahannan, M.D., MMEd, Associate Professor in the Section of
Hematology/Oncology at OU College of Medicine at the University of
Oklahoma Health Sciences and Presenting Author for the TTX-080
Phase 1 clinical trial. “The addition of TTX-080 to
standard-of-care cetuximab showed promising clinical activity in
subsets of biomarker-defined patients who have received multiple
lines of prior therapies, including chemotherapy, antiangiogenic
and immunotherapy agents. We look forward to additional studies
that further explore the role of TTX-080 for these
difficult-to-treat cancers in a high unmet need patient
population.”
Clinical Trial Results
Results from Ph1a/1b Analyses of TTX-080, a First-in-Class HLA-G
Antagonist, in Combination with Cetuximab in Patients with
Metastatic Colorectal Cancer and Head and Neck Squamous Cell
Carcinoma
The Phase 1 open-label, dose escalation and dose expansion
clinical trial of TTX-080 evaluated safety, tolerability,
recommended Phase 2 dose and preliminary efficacy of TTX-080 as
monotherapy and in combination with either cetuximab, an EGFR
inhibitor, or pembrolizumab, a PD-1 inhibitor, in patients with
advanced refractory/resistant solid tumors (n=240). The clinical
results that will be presented at ASCO focus on the safety and
efficacy from the Phase 1b cohorts of the trial, evaluating TTX-080
in combination with cetuximab in patients with anti-EGFR-naïve,
wild-type (WT) KRAS mCRC (n=25) and mHNSCC cancers (n=23), with a
data cutoff of April 15, 2024. Additional information about the
clinical trial can be found on clinicaltrials.gov
(NCT04485013).
TTX-080 was well tolerated as monotherapy and in combination
with cetuximab in patients with mCRC and mHNSCC.
Metastatic Colorectal Cancer Results
The most common Grade 3 adverse events (AEs) in patients with
mCRC were increases in AST (n=3) and ALT (n=3), fatigue (n=1),
dermatitis acneiform (n=1) and myalgias (n=1).
TTX-080 plus cetuximab demonstrated anti-tumor activity in
patients with WT RAS, BRAF, HER2-negative mCRC. Patients in this
subgroup had received a median of 2 prior lines of treatment (Range
1,5). All patients had received 5-fluoropyrimidine. Seventy-eight
percent (78%) of patients had received prior bevacizumab and more
than 75% had received oxaliplatin and or irinotecan. Median
progression-free survival (PFS) was 24.4 weeks, with a 36-week PFS
rate of 47%. In 14 tumor response evaluable patients with WT RAS,
BRAF, HER2-negative mCRC, TTX-080 plus cetuximab achieved an
overall best response (ORR) in 4 patients (29%), a partial response
(PR) in 4 patients (29%) and stable disease (SD) in 6 patients
(43%). Nine (9) of 13 (69%) patients had at least 15% target lesion
regression and 10 of 14 patients had disease control rate (DCR) of
greater than 90 days (71%).
Locally Advanced/Metastatic Head and Neck Squamous Cell
Carcinoma Results
The most common Grade 2 AEs were anemia (n=2), fatigue (n=1) and
an increase in AST (n=1). One (1) patient experienced Grade 4
anemia.
TTX-080 in combination with cetuximab generated anti-tumor
activity in patients with human papillomavirus (HPV)-negative
mHNSCC. Patients in this subgroup had received a median of 1 prior
line of treatment (Range 1, 2). All patients had received a prior
immunotherapy treatment. Median PFS was 23.9 weeks, with a 24-week
PFS rate of 43%. In 7 tumor response evaluable patients, TTX-080
plus cetuximab achieved an overall best response (ORR) in 4
patients (57%), 1 CR (14%), 3 PRs (43%) and 1 SD (14%). Five (5)
patients (71%) had at least 20% target lesion regression and DCR of
greater than 90 days (71%).
“These Phase 1b clinical results boost our confidence
that TTX-080 in combination with cetuximab may improve clinical
outcomes in patients with biomarker-defined advanced colorectal
cancer and head and neck squamous cell carcinoma,” said Swami
Murugappan, M.D., Ph.D., Consulting Chief Medical Officer at Tizona
Therapeutics. “Our goal is to confirm these Phase 1b results in
subsequent clinical trials.”
Translational Results
HLA-G, an MHC class I molecule expressed on solid tumors, is
known to drive immune suppression, promote cancer cell immune
escape and lead to tumor development and growth. HLA-G mediates
suppression through ILT2 and ILT4 on lymphoid (ILT2) and myeloid
(ILT2 & ILT4) cell subpopulations. TTX-080 is designed to block
HLA-G to reverse immune tolerance and activate anti-tumor immune
responses.
TTX-080 induced statistically significant on-mechanism immune
cell activation in the periphery and in the tumor. Peripheral
changes were detected using flow cytometry in patient peripheral
blood mononuclear cells (PBMCs). Increased percentages of activated
Ki67+ natural killer (NK) cells, - ILT2+ CD8+ T cells and of
activated Ki67+PD-1+HLA-DR+ CD4+ T cells. Monotherapy TTX-080 also
led to changes in the tumor, with the detection of increased
myeloid activation gene sets known to be associated with anti-tumor
activity.
Poster Details
Poster Session: Developmental Therapeutics –
ImmunotherapyDate/Time: June 1, 2024, at 9:00 a.m.
CDTAbstract: 2524 | Poster Board
#3Location: Hall A
About Tizona Therapeutics, Inc.
Tizona is a privately held, clinical-stage immunotherapy company
that develops first-in-class medicines to deliver transformational
benefits for people with cancer. Tizona translates scientific
breakthroughs into therapeutics that stimulate the immune system
and counter immune suppression. Tizona’s pipeline includes TTX-080,
which targets HLA-G and is being evaluated in a Phase 1b clinical
study in advanced cancers.
Media ContactLori
Murraylori.murray@captivate-comms.com