FDA Grants 2 Fast Track Designations to TT125-802 in EGFR/KRAS G12C NSCLC

TT125-802 monotherapy shrank the tumors in 5 of 7 patients with drug-resistant NSCLC, and no thrombocytopenia was observed.

The FDA has granted 2 fast track designations (FTD) to TT125-802, an orally available small-molecule inhibitor of CBP/p300, in patients with non–small cell lung cancer (NSCLC), according to a press release from the developer, TOLREMO therapeutics AG.¹

The first FTD was for those with locally advanced or metastatic NSCLC with an EGFR exon 19 deletion or exon 21 L858R substitution mutation and disease progression following at least 1 line of therapy including an EGFR inhibitor; the second FTD was for patients with locally advanced or metastatic KRAS G12C-mutated NSCLC and disease progression following at least 1 prior line of therapy including a KRAS G12Cinhibitor.

Promising initial data from the first-in-human phase 1 TT-CSP-001 trial (NCT06403436) evaluating the safety, tolerability, pharmacokinetics, and efficacy of TT125-802 in patients with advanced solid tumors who have relapsed or are refractory to standard-of-care therapies was shared virtually in a 2025 American Society of Clinical Oncology Annual Meeting data update.^2,3

TT125-802 monotherapy yielded multiple responses, shrinking tumors in 5 of 7 patients with drug-resistant NSCLC; patients with KRAS G12C and EGFR mutations demonstrated rapid, deep, and durable responses.

“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, said in the press release.¹ “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 [with] TT125-802 as a single agent in patients with drug-resistant KRAS-G12C- or EGFR-mutant NSCLC.”

The trial had an estimated enrollment of 50 patients who received oral TT125-802 as a single agent.

Eligible patients were 18 years or older with advanced solid tumors resistant or refractory to standard treatment; measurable disease per RECIST v1.1 criteria; an ECOG performance status of 0 or 1; adequate hematological, hepatic, and renal function; adequate coagulation laboratory assessments; and a life expectancy of at least 3 months.⁴

Exclusion criteria included clinically significant uncontrolled intercurrent illness, presence of brain metastases unless clinically stable, history or presence of malignancies unless curatively treated with no evidence of disease for at least 2 years, and known HIV or active viral hepatitis B/C. Patients were also deemd ineligible for trial enrollment if they had serious gastrointestinal bleeding within the past 3 months, receipt of a live vaccine; receipt of a strong CYP3A4 inhibitor, and hypersensitivity to the agent or any excipients of TT125-802.

The trial’s primary end points were the frequency and severity of adverse events (AEs) and serious AEs, frequency of dose interruptions and dose reductions, incidence of dose-limiting toxicities, and recommended doses for expansion. Secondary end points were plasma concentration of TT125-802 in blood, objective response rate per RECIST v1.1 criteria, duration of response, and progression-free survival.

It was reported that TT125-802 did not cause thrombocytopenia.

“TT125-802’s highly selective mechanism of action and favorable safety profile without thrombocytopenia differentiate it from other agents in the class,” said Alan Sandler, MD, a scientific advisory board member at TOLREMO, in the release.¹ “The 2 fast track designations highlight TT125-802’s broad potential to provide a new approach for tackling drug resistance and tumor survival in solid tumors, including EGFR- and KRAS-G12C mutant NSCLC. We are looking forward to working closely with the FDA to advance the clinical evaluation of TT125-802 as an innovative backbone therapy.”

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 28, 2025. https://tinyurl.com/mtbwh275
2. TOLREMO therapeutics announces TT125-802 is the first CBP/p300 bromodomain inhibitor to show clinical activity in solid tumors. News release. TOLREMO therapeutics. June 4, 2025. Accessed August 28, 2025. https://tinyurl.com/mujyc7jj
3. ASCO data update: T125-802: a best-in-class CBP/p300 bromodomain inhibitor with activity in solid tumors. News release. TOLREMO therapeutics. June 2025. Accessed August 28, 2025. https://tinyurl.com/3maerntp
4. 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 28, 2025. https://tinyurl.com/3xspsbse