The FDA granted a breakthrough therapy designation to sacituzumab tirumotecan (sac-TMT; Kelun Pharmaceutical, Merck) for the treatment of patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations—exon 19 deletion (19del) or exon 21 L858R—whose disease progressed while on or after tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy. This designation is based on data from the phase 2 expansion cohort of a phase 1/2 study that evaluated sac-TMT in patients with EGFR-mutated NSCLC.1
About the Trials
TroFuse-004
- Trial Name: Sacituzumab Tirumotecan (MK-2870) Versus Chemotherapy in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations (MK-2870-004)
- ClinicalTrials.gov ID: NCT06074588
- Sponsor: Merck Sharp & Dohme LLC
- Completion Date (Estimated): March 11, 2030
TroFuse-009
- Trial Name: Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) and Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009)
- ClinicalTrials.gov ID: NCT06305754
- Sponsor: Merck Sharp & Dohme LLC
- Completion Date (Estimated): June 14, 2030
Sac-TMT is an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody drug conjugate (ADC) being developed. It also contains an irreversible but hydrolyzable linker, which joins the monoclonal antibody and the cytotoxic payload leveraging proprietary linker conjugation technology. Internationally, sac-TMT recently received its first marketing authorization in for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer who have received at least 2 prior systemic therapies, at least 1 of which is for advanced or metastatic stage. This was based on results from the phase 3 OptiTROP-Breast01 study (NCT05347134).1
Currently, sac-TMT is undergoing evaluation as a monotherapy and in combination with pembrolizumab (Keytruda; Merck) in 10 ongoing phase 3 trials across various solid tumors.1 Of these, 2 include trials evaluating sac-TMT in NSCLC: TroFuse-004 (NCT06074588)2 and TroFuse-009 (NCT06305754).3
TroFuse-004 is an ongoing randomized, open-label phase 3 clinical trial assessing sac-TMT compared with chemotherapy (docetaxel [Taxotere; Sanofi] or pemetrexed [Alimta; Eli Lilly & Co]) in patients with previously treated EGFR-mutated or other genomic-altered NSCLC. Patients in the sac-TMT group will receive 4 mg/kg intravenous (IV) infusions of sac-TMT on days 1, 15, and 29 of each 6-week cycle, then diphenhydramine (or an equivalent), an H2 antagonist of investigator's choice, acetaminophen (or an equivalent), and dexamethasone (or an equivalent) per each drug's product label prior to the first 4 infusions of sac-TMT. The H2 antagonist and dexamethasone are optional at subsequent administrations. Those on chemotherapy will receive 75 mg/m2 of docetaxel or 500 mg/m2 of pemetrexed by IV infusion on days 1 and 22 of every 6-week cycle.2
TroFuse-009 is an ongoing randomized, open-label phase 3 study which is evaluating sac-TMT compared with doublet chemotherapy (pemetrexed plus carboplatin) in certain patients with previously treated EGFR-mutated NSCLC. Patients will receive 4 mg/kg IV infusions every 2 weeks on days 1, 15, and 29 of every 6-week cycle until discontinuation criteria is met. Those receiving chemotherapy will be administered 500 mg/m2 IV infusions of pemetrexed every 3 weeks—on days 1 and 22 of every 6-week cycle—plus area under the curve 5 mg/mL*min carboplatin every 3 weeks—on days 1 and 22 of every 6-week cycle for 4 doses—then 500 mg/m2 pemetrexed every 3 weeks until discontinuation criteria is met.3
For both trials, the primary outcome measures are progression-free survival (PFS) and overall survival (OS), which will be measured up to 35 months and 41 months, respectively, in TroFuse-004, and up to week 51 (both outcomes) in TroFuse-009. Secondary outcome measures include objective response rate, duration of response, time to deterioration, and number of adverse events.2,3
“This designation by the FDA highlights the importance of developing novel therapeutic options for patients living with EGFR-mutated nonsquamous NSCLC,” Scot Ebbinghaus, MD, vice president of global clinical development at Merck Research Laboratories, said in a news release. “We believe ADCs are an important modality in the treatment of cancer and are rapidly advancing the clinical development of sac-TMT, with the goal of meaningfully improving upon current standards of care in certain cancers.”1
REFERENCES
1. Businesswire. FDA Grants Breakthrough Therapy Designation to Sacituzumab Tirumotecan (sac-TMT) for the Treatment of Certain Patients With Previously Treated Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer With EGFR Mutations. News release. December 3, 2024. Accessed December 3, 2024. https://www.businesswire.com/news/home/20241203790598/en/FDA-Grants-Breakthrough-Therapy-Designation-to-Sacituzumab-Tirumotecan-sac-TMT-for-the-Treatment-of-Certain-Patients-With-Previously-Treated-Advanced-or-Metastatic-Nonsquamous-Non-Small-Cell-Lung-Cancer-With-EGFR-Mutations
2. Sacituzumab Tirumotecan (MK-2870) Versus Chemotherapy in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations (MK-2870-004). ClinicalTrials.gov identifier: NCT06074588. Updated December 2, 2024. Accessed December 3, 2024. https://clinicaltrials.gov/study/NCT06074588
3. Sacituzumab Tirumotecan (MK-2870) Versus Pemetrexed and Carboplatin Combination Therapy in Participants With Epidermal Growth Factor (EGFR)-Mutated, Advanced Nonsquamous Non-small Cell Lung Cancer (NSCLC) and Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors (MK-2870-009). ClinicalTrials.gov identifier: NCT06305754. Updated December 2, 2024. Accessed December 3, 2024. https://clinicaltrials.gov/study/NCT06305754
