FDA Grants Breakthrough Therapy Designation to CLN-081 for Locally Advanced/Metastatic EGFR Exon 20–Mutant NSCLC

Patients with locally advanced or metastatic EGFR exon 20–mutant non–small cell lung cancer may benefit from treatment with CLN-081, which was granted breakthrough therapy designation by the FDA.

CLN-081 received a breakthrough therapy designation from the FDA for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 mutations that has previously been treated with a systemic platinum-based chemotherapy regimen, according to a press release from developer Cullinan Oncology.1

The designation is intended to expedite the drug’s development and review.

“We are extremely pleased that Cullinan has received breakthrough therapy designation from the FDA for CLN-081, a distinction that underscores the urgent need to bring improved targeted treatments to this patient population and further supports the differentiated clinical profile of CLN-081,” Nadim Ahmed, chief executive officer at Cullinan Oncology, said in the press release. “The updated data from our ongoing phase 1/2a study in a larger number of patients have demonstrated a high response rate with durable responses and encouraging progression-free survival in heavily pre-treated patients. We are also encouraged by the favorable safety profile observed thus far, and we look forward to ongoing, productive regulatory discussions with the FDA, which are further enabled with this designation.”

Clinical data from a phase 1 study (NCT04036682) on the safety of CLN-081 were read out at the 2021 American Society of Clinical Oncology Annual Meeting.2 Patients were treated at 1 of several dose levels, including 30, 45, 65, 100, and 150 mg twice daily, with the 30, 65, and 100 mg doses being selected for the efficacy expansion.

Investigators reported that in terms of safety, 98% of patients experienced any grade treatment-related adverse effects (TRAEs), with 44% of patients experiencing TRAEs that were grade 3 or higher. Notably, patients did not need prophylactic treatment for gastrointestinal or skin toxicities. Common any grade TRAEs included rash (76%), diarrhea (22%), paronychia (22%), stomatitis (18%), nausea (18%), and anemia (18%). Grade 3 TRAEs included anemia (9%), alanine aminotransferase increase (4%), aspartate aminotransferase increase (4%), diarrhea (2%), amylase increase (2%), neutropenia (2%), and stomatitis (2%).

Among the 42 patients who were evaluable for response, 21 achieved a partial response (PR), 13 had a confirmed PR, and 8 had unconfirmed PRs following treatment with CLN-081. Additionally, 22 patients had stable disease and 1 experienced progressive disease. The treatment resulted in a disease control rate of 64% and 52% of patients were still on treatment at the data cutoff.

Findings from the phase 2 portion of the study indicated that 54% of patients experienced a PR following treatment with a 100 mg twice daily dose of CLN-081. Six of these responses were confirmed and 1 was unconfirmed.


  1. FDA grants breakthrough therapy designation for Cullinan Oncology’s CLN-081 in patients with locally advanced or metastatic EGFR mutated non-small cell lung cancer. News release. Cullinan Oncology. January 4, 2022. Accessed January 5, 2022. https://bit.ly/3qVHag9
  2. Piotrowska Z, Yu HA, Yang JC-H, et al. Safety and activity of CLN-081 (TAS6417) in NSCLC with EGFR exon 20 insertion mutations (Ins20). Presented at: American Society of Clinical Oncology Annual Meeting; June 4-8, 2021; Virtual. Abstract 9077.