TT125-802 Earns FDA Fast Track Designations for EGFR+ and KRAS G12C+ Advanced NSCLC

The FDA has granted a pair of fast track designations to the small molecule CBP/p300 bromodomain inhibitor TT125-802 for the treatment of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations, with disease progression on at least 1 line of prior therapy including an EGFR inhibitor; and for the treatment of patients with locally advanced or metastatic KRAS G12C–mutated NSCLC, with disease progression on at least 1 line of prior therapy including a KRAS G12C inhibitor.1

“NSCLC is a major cause of cancer-related death. While oncogene-targeting drugs such as EGFR and KRAS inhibitors improve overall survival, a significant number of patients eventually experience disease progression, representing a high unmet medical need,” Stefanie Flückiger-Mangual, PhD, chief executive officer at TOLREMO Therapeutics, stated in a news release. “TT125-802 has the potential to address this challenge by blocking transcriptional pathways that drive tumor growth and treatment evasion in parallel to the driving oncogene. This is supported by our clinical data to date, demonstrating deep and durable responses to TT125-802 as a single agent in patients with drug-resistant KRAS G12C– or EGFR-mutant NSCLC. The fast track designations in these indications provide us with an accelerated path on our mission to deliver our differentiated treatment approach to patients who urgently need it.”

Findings from the phase 1 TT-CSP-001 trial (NCT06403436) presented at the 2025 ASCO Annual Meeting showed that among treated patients with a variety of advanced solid tumors (n = 26), 7 patients experienced clinical benefit lasting more than 6 months, including 1 patient with NSCLC who achieved a confirmed partial response per RECIST 1.1 criteria.2

The agent was well tolerated. One dose-limiting toxicity (DLT; grade 3 hyperglycemia) was reported in a patient treated at a dose of 60 mg twice per day. Notably, 98% of treatment-related adverse effects (AEs) were grade 1 or 2, and no instances of thrombocytopenia were reported. The most common AEs included dysgeusia, hyperglycemia, anemia, elevated liver and pancreatic enzymes levels, stomatitis, fatigue, and decreased appetite.

TT-CSP-001 Overview

The first-in-human, open-label study is evaluating TT125-802 as a single agent in patients at least 18 years of age with advanced solid tumors that are resistant or refractory to standard treatment.3 Patients are also required to have an ECOG performance status of 0 or 1; adequate hepatic, renal, and coagulation function; and a life expectancy of more than 3 months. Patients with brain metastases were excluded unless they were clinically stable.

In the population treated ahead of the data cutoff for the ASCO presentation, patients had adenoid cystic carcinoma (n = 4), ampullary carcinoma (n = 1), anal cancer (n = 2), breast cancer (n = 2), colorectal cancer (n = 3), dedifferentiated liposarcoma (n = 1), enteroid adenocarcinoma (n = 1), malignant cylindroma (n = 1), castration-resistant prostate cancer (n = 2), NSCLC (n = 5), NUT carcinoma (1), pancreatic ductal adenocarcinoma (n = 1), thymic cancer (n = 1), and undifferentiated pleomorphic sarcoma (n = 1).2

These patients received TT125-802 at doses ranging from 15 mg once per day to 100 mg once per day, as well as 60 mg twice today while fasted and 30 mg once per day with food.

Safety and the incidence of DLTs are serving as the trial’s primary end points.3 Secondary end points include pharmacokinetics, objective response rate, duration of response, and progression-free survival.

References

1. TOLREMO Therapeutics receives two FDA fast track designations for TT125-802 in pretreated, advanced or metastatic NSCLC with either an EGFR or a KRAS-G12C mutation. News release. TOLREMO Therapeutics. August 28, 2025. Accessed August 29, 2025. https://www.tolremo.com/press-releases/2025/8/28/tolremo-therapeutics-receives-two-fda-fast-track-designations-for-tt125-802-in-pretreated-advanced-or-metastatic-nsclc-with-either-an-egfr-or-a-kras-g12c-mutation
2. Boni V, Antrás JF, Garralda E, et al. TT125-802, a highly selective, well-tolerated bromodomain inhibitor of CBP/p300 with anti-tumor activity in patients with advanced solid tumors: an update on the ongoing phase I study. J Clin Oncol. 2025;43(suppl 16):e15105. doi:10.1200/JCO.2025.43.16_suppl.e15105
3. A study evaluating the safety, tolerability, pharmacokinetics, and efficacy of TT125-802 in subjects with advanced solid tumors (TT-CSP-001). ClinicalTrials.gov. Updated May 21, 2025. Accessed August 29, 2025. https://www.clinicaltrials.gov/study/NCT06403436