FDA Grants Breakthrough Therapy Designation to Sac-TMT for Some with NSCLC

A breakthrough therapy designation has been granted for sacituzumab tirumotecan by the FDA for patients with NSCLC.

The Food and Drug Administration (FDA) has granted a breakthrough therapy designation to the antibody-drug conjugate (ADC) sacituzumab tirumotecan (sac-TMT, also known as MK-2870 and SKB264) for the treatment of certain patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC).

Specifically, patients eligible for treatment have epidermal growth factor receptor (EGFR) mutations (exon 19 deletion or exon 21 L858R) whose disease has progressed on or after treatment with a tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy.

“This designation by the FDA highlights the importance of developing novel therapeutic options for patients living with EGFR-mutated nonsquamous non-small cell lung cancer,” said Dr. Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories, in a news release issued by Merck, the drug’s manufacturer. “We believe ADCs are an important modality in the treatment of cancer and are rapidly advancing the clinical development of sacituzumab tirumotecan, with the goal of meaningfully improving upon current standards of care in certain cancers.”

The designation, according to the news release, is based on findings from the phase 2 expansion cohort of a phase 1/2 study that is evaluating sac-TMT among patients with EGFR-mutated NSCLC which were previously presented at the American Society of Clinical Oncology (ASCO) meeting in 2023 in addition to data from two parts of a phase 2 study evaluating the treatment in patients with EGFR-mutated NSCLC who were previously treated with at least two lines of therapy.

READ MORE: FDA Receives Application for Dato-DXd Treatment in EGFR-Mutated NSCLC

Merck, according to its news release, is currently evaluating sac-TMT as both a standalone monotherapy and in combination with Keytruda (pembrolizumab), and there are currently 10 ongoing phase 3 studies being conducted across various solid tumor types, the company stated.

These trials include TroFuse-004, in which researchers are studying sac-TMT versus chemotherapy in patients with previously treated NSCLC with EGFR mutations or other genetic alterations, and the TroFuse-009 clinical trial weighing sac-TMT versus doublet chemotherapy in some patients with previously treated EGFR-mutated NSCLC.

Sac-TMT, according to the National Cancer Institute, is now being studied in 13 clinical trials in tumor types including, in addition to NSCLC, endometrial cancer, gastrointestinal cancers, gastroesophageal adenocarcinoma, cervical cancer, urothelial carcinoma, breast cancer and bladder cancer.

In a poster presented at ASCO in 2023, the overall objective response rate (ORR) among patients with non-small cell lung cancer was 43.6%, with a median duration of response of 9.3 months and a six-month duration of response rate of 77.4%. The median progression-free survival was 6.2 months and the 12-month overall survival rate was 70.6%. Among patients with TKI-resistant EGFR-mutant NSCLC, half of whom had failed at least one line of chemotherapy, the ORR was 60% and the disease control rate was 100%.

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