TT125-802 Gains FDA Fast Track Designation in NSCLC

A novel small-molecule bromodomain inhibitor, TT125-802, has received 2 fast track designations from the US FDA for the treatment of non–small cell lung cancer (NSCLC).¹ This dual designation is aimed at patients with locally advanced or metastatic NSCLC who have experienced disease progression on at least 1 prior line of therapy, including either an EGFR inhibitor or a KRAS G12C inhibitor. The designations underscore the potential of TT125-802, a drug developed by Tolremo Therapeutics AG, to address a critical unmet medical need in patients who have exhausted standard targeted therapies.

The FDA's fast track program is designed to expedite the development and review of new drugs that treat serious conditions and have the potential to address an unmet medical need. This status will enable Tolremo to engage in more frequent communication with the FDA throughout the development process, with the goal of bringing the therapy to patients more rapidly.

“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,” said Stefanie Flückiger-Mangual, PhD, CEO at Tolremo, in a press 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.”

Clinical Rationale and Evidence

The fast track designations are supported by encouraging initial efficacy and safety data from an ongoing first-in-human phase 1 clinical trial (NCT06403436). The trial, designed to evaluate the safety, tolerability, pharmacokinetics, and efficacy of TT125-802 in patients with advanced solid tumors, presented promising results at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting.

Initial data from the monotherapy dose-escalation portion of the study demonstrated impressive clinical activity, including deep and durable objective responses in patients with drug-resistant KRAS-G12C- or EGFR-mutant NSCLC. A notable finding from the trial was the drug's safety profile, which was described as best-in-class within its class of inhibitors. Specifically, TT125-802 did not cause thrombocytopenia, a common dose-limiting toxicity associated with other CBP/p300 bromodomain inhibitors. This favorable safety profile allows for higher dosing, which is often required to achieve a meaningful anti-tumor effect.

The study’s primary end point are frequency and severity of adverse events, frequency of dose interruptions and discontinuations, incidence of dose-limiting toxicities, and recommended dose(s) for expansion.²

Mechanism of Action

TT125-802 is an orally available, small-molecule inhibitor of the bromodomain of CREB-binding protein (CBP) and E1A-associated protein (p300).¹ The mechanism of action is distinct from conventional oncogene-targeting therapies. Instead of directly inhibiting the primary oncogenic pathway (eg, EGFR or KRAS), TT125-802 targets what the company refers to as “non-oncogene addiction." This refers to a fundamental driver of cancer cell survival and treatment resistance that operates in parallel to the primary oncogenic pathways. By blocking the bromodomain of CBP/p300, the drug aims to disrupt transcriptional escape pathways that lead to both intrinsic and acquired resistance to targeted therapies. This innovative approach is designed to prevent cancer cells from activating alternative survival mechanisms when the primary oncogene is inhibited.

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/5n8nwder

2. 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. August 28, 2025. https://clinicaltrials.gov/study/NCT06403436