Tizona Therapeutics Presents Phase 1b TTX-080 Clinical Data in Advanced Colorectal Cancer and Head and Neck Squamous Cell Carcinoma at ASCO 2024

2024-05-23

免疫疗法临床1期临床结果ASCO会议

TTX-080 plus EGFR Inhibitor EGFR Inhibitor Cetuximab Demonstrated Promising Evidence of Clinical Activity in Patients with Biomarker-Defined Metastatic Colorectal Cancer and Locally Advanced/Metastatic Head and Neck Squamous Cell Carcinoma

TTX-080 Exhibited Significant On-Mechanism Immune Cell Changes in the Periphery and in Tumors

SOUTH SAN FRANCISCO, Calif., May 23, 2024 (GLOBE NEWSWIRE) -- 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 – Immunotherapy

Date/Time: June 1, 2024, at 9:00 a.m. CDT

Abstract: 2524 | Poster Board #3

Location: 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 Contact

Lori Murray

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