NEW YORK – AbbVie's MET-targeting antibody-drug conjugate telisotuzumab vedotin led to durable responses in patients with c-MET-overexpressing EGFR-wild-type non-small cell lung cancer in a Phase II study.
The results from the LUMINOSITY trial, presented at the International Association for the Study of Lung Cancer's World Conference on Lung Cancer (WCLC) in San Diego on Tuesday, bolster AbbVie's confidence in the c-MET expression cutoff it has established in an ongoing Phase III trial testing telisotuzumab vedotin's activity in previously treated NSCLC patients.
Patients with c-MET-overexpressing NSCLC often have a poorer prognosis. In the LUMINOSITY trial, researchers aimed to measure the safety and efficacy of telisotuzumab vedotin and determine the level of c-MET expression at which patients are likely to respond to treatment.
In the trial, researchers used immunohistochemistry testing to stratify patients based on high or intermediate c-MET overexpression, Hidehito Horinouchi, a medical oncologist in the department of thoracic oncology at the National Cancer Center Hospital in Tokyo, said during a presentation at the meeting. Patients were high expressers if they expressed c-MET in at least 50 percent of tumor cells with an IHC 3+ score, and patients with c-MET expression in 25 percent to 50 percent of tumors cells and an IHC 3+ score were deemed intermediate expressers.
In the overall study cohort of 161 patients, the objective response rate on telisotuzumab vedotin was 28.6 percent. Among 78 patients with high c-MET expression, the response rate was slightly higher at 34.6 percent compared to a 22.9 percent response rate among 83 intermediate expressers.
The high expressers also had a longer duration of response, nine months versus 7.2 months for intermediate expressers. Nearly two-thirds of high expressers, or 63 percent, had a duration of response longer than six months, while nearly half of intermediate expressers, or 47.4 percent, responded for six months or longer. Overall, regardless of high or intermediate c-MET expression status, 56.5 percent of all patients in the study responded for six months or longer on telisotuzumab vedotin.
"Of note, these patients are in the second- and third-line [treatment setting], where the usual standard of care with docetaxel shows around a 50 percent response," Horinouchi said.
The researchers also explored the efficacy of telisotuzumab vedotin in a subgroup of 48 Asian patients, in whom the response rate was 35.4 percent. Stratified by c-MET expression, the response rate was 46.2 percent among 26 Asian patients with high expression and 22.7 percent among 22 Asian patients with intermediate expression.
The median progression-free survival was similar regardless of c-MET expression among Asian patients, at around 5.5 months. Asian patients with high expression had a numerically longer median overall survival, 25.4 months, compared to 17 months for intermediate expressers.
"The Asian subgroups showed a better response rate and better efficacy [on this treatment]," Horinouchi said. "When we selected for the patient population with c-MET high [expression], nearly half of the patients responded to this agent."
Federico Cappuzzo, director of medical oncology at the National Cancer Institute Regina Elena in Rome, who discussed the LUMINOSITY results at WCLC, noted that the difference seen in outcomes between Asian patients and the overall study population may be explained by patients' characteristics. He noted that the Asian subgroup had more never smokers and fewer patients with brain metastases, factors associated with better prognosis.
Even if Asian patients appeared to fare better on telisotuzumab vedotin, the data from LUMINOSITY showed that "this agent is potentially effective in the c-MET-positive [NSCLC] patients regardless of ethnicity," Cappuzzo concluded.
The most common adverse event seen with telisotuzumab vedotin treatment was peripheral sensory neuropathy, accounting for 30.2 percent of all adverse events and 7 percent of grade 3 or higher adverse events. Two patients died in the study from adverse events, one due to interstitial lung disease (ILD) and another due to respiratory failure. Overall, 9.9 percent of patients in the study experienced ILD on treatment.
Horinouchi noted that the adverse events seen in the trial, such as ILD, were known about the drug, and no new safety signals emerged in LUMINOSITY. Moreover, ILD is a common issue with antibody-drug conjugates, he said, adding that the field "must find a biomarker" that predicts which patients are at risk for this adverse event.
The Phase III trial of telisotuzumab vedotin underway in previously treated NSCLC is enrolling patients globally who have c-MET expression in more than 25 percent of tumor cells and an IHC 3+ score.
Telisotuzumab vedotin is a potential first-in-class agent, but there are other pharmas exploring treatments for c-MET-expressing tumors, such as Mythic Therapeutics' c-MET-targeting antibody-drug conjugate MYTX-011 and Fusion Pharmaceuticals' radiopharmaceutical [225AC]-FPI-2068 and accompanying imaging agent [111ln]-FPI-2107, being studied in solid tumors expressing EGFR and c-MET.