Tizona Therapeutics has broadened its ongoing Phase Ib clinical trial for TTX-080, an innovative antibody targeting human leukocyte antigen-G (HLA-G), to include additional arms focusing on metastatic colorectal cancer (mCRC) patients identified by specific biomarkers. This expansion aims to further evaluate the efficacy of TTX-080 in combination therapies for a defined subset of mCRC patients.
Trial Design and Patient Population
The expanded trial incorporates two randomized arms designed to assess the effectiveness of TTX-080 when administered with cetuximab and FOLFIRI as a second-line treatment. The study will enroll mCRC patients who are microsatellite stable (MSS), wild type (WT) RAS, WT BRAF, and human epidermal growth factor receptor 2 (HER2)-negative. These patients will have previously undergone treatment with fluorouracil (5-FU) and oxaliplatin in the first-line or adjuvant setting and experienced a relapse within six months, representing a population with limited treatment options.
Endpoints and Objectives
The trial's primary endpoint is the overall response rate (ORR), a key indicator of anti-tumor activity. Secondary endpoints include a comprehensive evaluation of safety, duration of response (DoR), median progression-free survival (PFS), and median overall survival (OS). These measures will provide a thorough understanding of the clinical benefit and tolerability of the TTX-080 combination therapy.
Prior Clinical Data
In May, Tizona Therapeutics reported data from an open-label, dose-escalation, and expansion Phase 1 trial of TTX-080. This earlier trial assessed the safety, tolerability, recommended Phase II dose, and initial efficacy of TTX-080 as a single agent and in combination with cetuximab or pembrolizumab in patients with advanced, refractory, or resistant solid tumors. The findings indicated that TTX-080 demonstrated good tolerability as a monotherapy and in combination with cetuximab in mCRC and metastatic head and neck squamous cell carcinoma (mHNSCC) patients.
Background and Previous Studies
In October 2021, Tizona initiated a Phase Ib expansion study to evaluate the safety and efficacy of TTX-080 as a single agent and in combination with pembrolizumab or cetuximab in patients with advanced refractory or resistant solid tumor malignancies. This study included patients with head and neck squamous cell carcinoma (HNSCC), non-small cell lung cancer (NSCLC), colorectal cancer, and triple-negative breast cancer. The study also evaluated the anti-tumor activity of TTX-080, as well as its safety, pharmacokinetics, immunogenicity, and potential biomarkers.
