AbbVie Submits BLA to Telisotuzumab Vedotin for NSCLC

A supplemental biologics license application was submitted for telisotuzumab vedotin for the treatment of metastatic EGFR wild-type nonsquamous non–small cell lung cancer.

AbbVie submitted a biologics license application (BLA) to the FDA seeking accelerated approval for telisotuzumab vedotin (Teliso-V) in adults with pretreated, locally advanced or metastatic EGFR wild-type nonsquamous non–small cell lung cancer (NSCLC) that has c-Met protein overexpression.¹

The investigational antibody-drug conjugate (ADC) was designed to target tumors with overexpression of c-Met, a receptor tyrosine kinase associated with overexpression in several solid tumor types, such as NSCLC. The FDA previously granted breakthrough therapy designation to Teliso-V for this indication in January 2022.²

Supporting data for the BLA came from the phase 2 LUMINOSITY trial (NCT03539536) assessing Teliso-V monotherapy in patients with c-Met overexpressing NSCLC. Updated findings from LUMINOSITY were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.³

Among patients with high expression (n = 78), intermediate expression (n = 83), and overexpression of c-Met overall (n = 161), treatment with Teliso-V elicited an objective response rate (ORR) of 34.6% (95% CI, 24.2%-46.2%), 22.9% (95% CI, 14.1%-33.4%), and 28.6% (95% CI, 21.7%-36.2%), respectively. Additionally, the median duration of response (DOR) was 9.0 months (95% CI, 4.2-13.0), 7.2 months (95% CI, 5.3-11.5), and 8.3 months (95% CI, 5.6-11.3) in each respective cohort. Responses lasting for 6 months or longer were reported in 63.0%, 47.4%, and 56.5% of patients in each group.

Teliso-V produced a median progression-free survival (PFS) of 5.5 months (95% CI, 4.1-8.3) in the c-Met high group, 6.0 months (95% CI, 4.5-8.1) in the c-Met intermediate group (95% CI, 4.5-8.1), and 5.7 months (95% CI, 4.6-6.9) in the total c-Met overexpression group. Across each respective cohort, the median overall survival (OS) was 14.6 months (95% CI, 9.2-25.6), 14.2 months (95% CI, 9.6-16.6), and 14.5 months (95% CI, 9.9-16.6). Investigators noted that 41.0% of patients received an additional line of systemic therapy after discontinuing Teliso-V.

Any-grade treatment-related adverse effects (TRAEs) occurred in 81.4% of patients, and 27.9% had grade 3 or higher TRAEs. Common any-grade TRAEs included peripheral sensory neuropathy (30.2%), peripheral edema (16.3%), fatigue (14.0%), and diminished appetite (11.6%). Overall, investigators noted no new safety signals associated with Teliso-V.

“Patients with [NSCLC] have unmet medical needs and oncologists are looking for new treatment options for these patients who unfortunately have a poor prognosis. We are hopeful that Teliso-V will be a differentiated treatment for certain patients as we look toelevate the standards of care in oncology,” Roopal Thakkar, MD, executive vice president of Research and Development and chief scientific officer at AbbVie, stated in the press release.¹

In the multicenter, non-randomized phase 2 LUMINOSITY trial, patients were assigned to receive Teliso-V at 1.9 mg/kg every 2 weeks.

Patients 18 years and older with advanced or metastatic NSCLC and c-Met overexpression based on immunohistochemistry were eligible for enrollment on the trial. Those with 2 or fewer prior lines of systemic therapy in the advanced or metastatic setting, including cytotoxic chemotherapy, immunotherapy, and agents targeting driver gene alterations were also able to enroll on the trial.

The trial’s primary end point was ORR based on independent central review using RECIST v1.1 criteria. Secondary end points included disease control rate, DOR, PFS, and OS.

According to the press release, investigators are also evaluating treatment with Teliso-V monotherapy in those with previously treated NSCLC harboring c-Met overexpression in the confirmatory phase 3 TeliMET NSCLC-01 trial (NCT04928846).

References

1. AbbVie submits biologics license application to the FDA for telisotuzumab vedotin (Teliso-V) in previously treated non-small cell lung cancer. News release. AbbVie. September 27, 2024. Accessed October 7, 2024. https://tinyurl.com/342fntt7

2. AbbVie announces U.S. 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 October 7, 2024. https://tinyurl.com/25tzhdpz

3. Camidge DR, Bar J, Horinouchi H, et al. Telisotuzumab vedotin monotherapy in patients with previously treated c-Met–overexpressing non-squamous EGFR wildtype advanced NSCLC: primary analysis of the LUMINOSITY trial. J Clin Oncol. 2024;42(suppl 16):103. doi: 10.1200/JCO.2024.42.16_suppl.103