FDA Grants BTD to Telisotuzumab Vedotin in EGFR Wild-Type Non–Small Cell Lung Cancer

Telisotuzumab vedotin’s breakthrough therapy designation for EGFR wild-type non–small cell lung cancer was supported by results from the phase 2 LUMINOSITY trial.

The FDA has granted a breakthrough therapy designation to telisotuzumab vedotin (teliso-V) for patients with advanced or metastatic EGFR wild-type nonsquamous non–small cell lung cancer with high levels of c-Met overexpression who have progressed on a platinum-based therapy, according to a press release from AbbVie.1

The designation is based on data from the phase 2 LUMINOSITY (NCT03539536) trial, which examined a population of patients with NSCLC and c-Met overexpression who could benefit from treatment with teliso-V. Findings from a previously reported analysis indicated that patients in the c-Met high group had an overall response rate (ORR) of 53.8%, and those in the c-Met intermediate group had an ORR of 25.0%.

“Patients with non–small cell lung cancer have a high unmet need and teliso-V has the potential to provide them with an additional treatment option to manage their disease. Today's announcement marks an important step in our mission to advance new oncology treatments across tumor types to improve standards of care for patients with cancer,” Mohamed Zaki, MD, PhD, vice president and global head of oncology clinical development at AbbVie, said in the press release.

Results from the open-label, single arm study, which were previously presented at the 2021 American Association for Cancer Research Annual Meeting, indicated that approximately 150 patients enrolled in stage 1, with up to 160 patients in stage 2. Those who enrolled were given teliso-V intravenously at a dose of 1.9 mg/kg every 2 weeks.2

Intermediate c-Met expression was defined as staining between 25% to 50% of tumor cells with 3+ intensity, and c-Met high was defined as staining 50% or higher with 3+ intensity. Those with squamous histology had c-Met staining of 75% or higher with 1+ intensity.

During the presentation, investigators presented results from 90 evaluable patients from stage 1 of the study. Within the non-squamous EGFR wild-type cohort, MET amplifications were observed in 5% of patients, and 11% had MET exon 14 skipping mutations. Additionally, patients across all cohorts received a median of 2 prior systemic therapies such as platinum-based regimens and immunotherapy.

The EGFR wild-type group (n = 37) had an ORR of 35.1% (95% CCI, 20.2%-52.5%) by independent central review (ICR) and an investigator assessed ORR of 36.1% (95% CI, 20.8%-53.8%). Within this cohort, the duration of response (DOR) for patients in the c-Met intermediate subgroup was 6.9 months. The ORR in the EGFR-mutant group (n = 30) was 13.3% (95% CI, 3.8%-30.7%) by ICR and 25.8% (95% CI, 11.9%-44.6%) when assessed by investigators. Additionally, an ORR of 18.2% (95% CI, 5.2%-40.3%) by ICR was reported in the c-Met high group, as well as 36.4% (95% CI, 17.2%-59.3%) when assessed by investigators. Of the 21 evaluable patients in the squamous cell cohort 3 responded with a median DOR of 4.4 months.

Grade 3 treatment-emergent adverse effects (TEAE) occurred in 30% to 50% of patients across the different cohorts. Across the EGFR wild-type, EGFR mutant, and squamous cohorts, 34%, 21%, and 36%, respectively, experienced a TEAE that lead to treatment discontinuation. In the non-squamous, EGFR wild-type cohort, the most significant any grade TEAEs were peripheral edema (21%) and peripheral sensory neuropathy (21%), with key grade 3 or higher TEAEs including pneumonia (6%), peripheral sensory neuropathy (4%), and pneumonitis (2%). Eighteen percent of patients in the non-squamous EGFR mutant cohort had any grade of peripheral edema and 21% had peripheral sensory neuropathy. Grade 3 or higher AEs included pneumonia (5%) and pneumonitis (3%). Lastly, 11% and 7% of patients with squamous histology experienced any grade of peripheral edema and peripheral sensory neuropathy, with grade 3 TEAEs including pneumonia (4%), peripheral sensory neuropathy (4%), and pneumonitis (4%).


1. AbbVie announces US FDA granted breakthrough therapy designation (BTD) to telisotuzumab vedotin (teliso-v) for previously treated non–small cell lung cancer. News Release. AbbVie. January 4, 2022. Accessed January 4, 2022. https://prn.to/3JDIIDT

2. Camidge DR, Moiseenko F, Cicin I, et al. Telisotuzumab vedotin (teliso-v) monotherapy in patients with previously treated c-Met+ advanced non-small cell lung cancer. Poster presented at the American Association for Cancer Research Annual Meeting 2021; April 10-15, 2021; Virtual. Abstract CT179. Accessed January 4, 2022. https://bit.ly/32lwmvX