Novel Small Molecule Earns FDA Fast Track Designation in ALK+ NSCLC

The FDA has granted fast track designation to TRI-611, an investigational molecular glue degrader therapy, as a treatment for those with ALK-positive non–small cell lung cancer (NSCLC), according to a press release from the developer, TRIANA Biomedicines, Inc.¹

Developers engineered TRI-611 as an orally available investigational agent that targets ALK fusion proteins among patients with NSCLC. The therapy causes ALK fusion proteins to converge with the E3 ligase enzyme cereblon with a unique binding mechanism that functions regardless of the ALK active site. Additionally, the agent leverages an innate protein-degradation system to selectively attack ALK fusion proteins while potentially overcoming limitations reported with other available ALK inhibitors.

“This fast track designation underscores the potential of TRI-611 to address the significant unmet need for patients with [ALK-positive] NSCLC who have been previously treated with 2 or more ALK tyrosine kinase inhibitors,” Patrick Trojer, PhD, president and chief executive officer of TRIANA, stated in the press release.¹ “TRI-611 was designed as an innovative therapeutic approach to target ALK fusion proteins. We look forward to working closely with the FDA to potentially bring TRI-611 forward to [the community of patients with lung cancer].”

Investigators are currently evaluating the safety, pharmacokinetics, and preliminary activity of TRI-611 among patients with ALK-positive NSCLC as part of a phase 1/2 study (NCT07491497). During the phase 1 portion of the trial, investigators will assess patients who have previously received standard-of-care ALK tyrosine kinase inhibitors (TKIs). The part 2 portion of the trial will determine the efficacy and safety of the agent across different patient populations.

Specifically, the part 2 portion of the study will include 3 different patient cohorts.² Cohort M1 will include those who previously received lorlatinib (Lorbrena) only in the second-line setting or later, cohort M2 will recruit those who received prior lorlatinib and neladalkib in the second-line setting or later, and cohort M3 will assess those without prior ALK TKI therapy exposure.

The trial’s primary end points include treatment-emergent adverse effects in part 1 as well as objective response rate (ORR) and depth of response in part 2. Secondary end points across both portions of the study include the half-life of TRI-611, maximum plasma concentration, duration of response, disease control rate, clinical benefit rate, progression-free survival, overall survival, central nervous system (CNS) ORR, CNS duration of response, time to intracranial progression, and profile changes in tumor ALK fusion protein levels.

Patients 18 years and older with pathologically confirmed ALK-positive NSCLC, measurable disease based on RECIST v1.1 guidelines, and adequate bone marrow reserve and organ function were eligible for enrollment on the trial. Prior treatment with 2 to 3 ALK TKIs was a requirement for entering part 1 of the study.

Those with additional driver alterations known to show resistance to ALK TKIs or CNS conditions associated with progressive neurological symptoms or those require increasing corticosteroid doses were ineligible for study entry. Patients were also unable to enroll if they had ongoing therapy with another anti-cancer agent or investigational treatment or major surgery within 4 weeks of beginning study treatment.

Earlier in March 2026, developers announced that the first patient had received a dose of TRI-611 as part of the phase 1/2 trial.³

“We are excited to have TRI-611 in the clinic and to advance this new potential therapy for [patients] living with lung cancer. Despite progress in treatments, many patients continue to [have] limited options,” Caroline Germa, MD, chief medical officer of TRIANA, said at the time of the first patient beginning treatment.³ “This study represents an important step in our mission to develop innovative therapies that may ultimately improve outcomes for [patients with ALK-positive] NSCLC and their families.”

References

1. TRIANA Biomedicines’ TRI-611 granted U.S. FDA fast track designation for treatment of ALK positive non-small cell lung cancer. News release. TRIANA Biomedicines, Inc. March 25, 2026. Accessed March 26, 2026. https://tinyurl.com/5a6m93tt
2. A phase 1/​2 study of TRI-611 in ALK-positive NSCLC. ClinicalTrials.gov. Updated March 25, 2026. Accessed March 26, 2026. https://tinyurl.com/mrn46zjb
3. TRIANA Biomedicines announces first patient dosed in a phase 1/2 trial evaluating TRI-611 for the treatment of ALK positive non-small cell lung cancer. News release. TRIANA Biomedicines, Inc. March 19, 2026. Accessed March 26, 2026. https://tinyurl.com/bdsdxv2b