FDA Grants BTD to Novel EGFR Inhibitor for Locally Advanced or Metastatic EGFR Exon 20+ NSCLC


The FDA has granted breakthrough therapy designation to CLN-081 for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor (EGFR) exon 20 insertion mutations who have previously received platinum-based systemic chemotherapy, announced Cullinan Oncology, Inc, in a press release.

“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,” said Nadim Ahmed, chief executive officer of Cullinan Oncology.

CLN-081, an orally available, irreversible EGFR inhibitor, has been shown to target cells that express EGFR exon 20 insertion mutations while simultaneously bypassing cells that express wild-type EGFR. Following platinum-based systemic chemotherapy, the agent is currently being investigated in a phase 1/2a, open-label, multi-center trial. In approximately 80 patients, the study will explore the safety and preliminary efficacy of the novel agent in 2 dose-escalation cohorts as well as 2 dose-expansion cohorts.

The study will assess the rate and severity of treatment-emergent adverse events (AEs) and dose-limiting toxicities, the incidence of laboratory assessment abnormalities, and the overall response rate (ORR) in patients treated in the phase 2a dose-expansion cohorts. The secondary end points of the study include ORR, duration of response, disease control rate, progression-free survival, overall survival, assessment of maximum concentration, area under the curve, time to maximum concentration, terminal half-life, and mean residence time.

Patients are eligible to enroll in the study given they are at least 18 years old with histologically or cytologically confirmed disease, a documented EGFR exon 20 insertion mutation, have received prior treatment in the recurrent/metastatic disease setting, have measurable disease per RECIST v1.1, have an ECOG performance status of 0 or 1, and have adequate laboratory values. All patients in the study must be able to take oral drugs.

The study excludes those who were previously treated with an EGFR inhibitor, a systemic anticancer therapy ≤ 14 days of study enrollment, radiotherapy ≤ 28 days of study enrollment, immunotherapy ≤ 28 days, and those who have undergone major surgery ≤ 28 days of joining the study. Patients previously treated with the investigation study drug are also excluded. Further, any patient with unresolved grade ≥ 2 toxicity from anticancer therapy is not eligible to enroll. Patients with suspected brain metastases and conditions that may interfere with study treatment were also excluded.

“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, said Ahmed, in the press release.


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. January 4, 2021. Accessed January 4, 2021. https://bit.ly/3pUIj8q

A phase 1/2a Trial of CLN-081 in patients with non-small cell lung cancer. Clinicaltrials.gov. Accessed January 4, 2021. https://bit.ly/3t2bZT3

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