Telisotuzumab Vedotin Meets Clinical End Points in LUMINOSITY Trial in Previously Treated NSCLC

Telisotuzumab vedotin (Teliso-V) produced meaningful response rates and other clinically relevant outcomes in patients with c-Met protein overexpressed, EGFR wild-type, advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC), according to topline findings from the single-arm, phase 2 LUMINOSITY/M14-239 trial (NCT03539536).¹

Per independent central review (ICR), the objective response rate (ORR) was 35% in patients with c-Met–high expression and 23% in patients with c-Met–intermediate expression. Additionally, the IRC-assessed median duration of response (DOR) was 9 months and 7.2 months in the c-Met–high and c-Met–intermediate populations, respectively. The median overall survival (OS) was similar in patients with c-Met–high and c-Met–intermediate disease, at 14.6 months and 14.2 months, respectively.

The toxicity profile of Teliso-V was consistent with prior results, and no new safety signals were reported. Treatment-related adverse effects (AEs) were manageable and tolerated. Full data from the trial will be presented at an upcoming medical meeting and discussed with global health agencies to support potential accelerated approval.

"The results of the phase 2 LUMINOSITY trial are encouraging for those patients with NSCLC with c-Met overexpression, as there is a critical need for better care and additional therapy options for them," Ross Camidge, MD, PhD, of the University of Colorado Cancer Center and principal study investigator, stated in a news release. "Today's announcement also provides confidence as we continue to enroll patients into the phase 3 TeliMET NSCLC-01 trial [NCT04928846] and expand our understanding of Teliso-V's potential."

c-Met is a tyrosine kinase receptor that is commonly overexpressed in many solid tumors and is present in approximately 25% of patients with advanced EGFR wild-type NSCLC. Currently, patients with c-Met overexpression have poor prognosis and no FDA-approved treatment options. Teliso-V is a first-in-class, c-Met protein–directed antibody-drug conjugate under study in several settings.

In January 2022, the FDA granted a breakthrough therapy designation to Teliso-V for patients with advanced or metastatic EGFR wild-type, nonsquamous NSCLC who have high levels of c-Met overexpression and whose disease has progressed on, or after, platinum-based chemotherapy.²

The designation was based on results from an interim analysis of the phase 2 LUMINOSITY trial, in which second- or third-line treatment with Teliso-V led to an ORR of 53.8% in patients with EGFR wild-type, nonsquamous NSCLC and high c-Met expression; the ORR was 25.0% in those with intermediate c-Met expression.

The trial enrolled patients with locally advanced or metastatic squamous or nonsquamous NSCLC whose tumors were c-Met overexpressed by central immunohistochemistry (IHC).³

Patients could not have received more than 2 prior lines of systemic therapy, including more than 1 line of chemotherapy. In the nonsquamous population c-Met overexpression was defined as intermediate (IHC 3+, ≥25% to < 50%) or high (IHC 3+, ≥50% 3+); 75% or greater expression (IHC 1+) was required in the squamous population.

Eligible patients received 1.9 mg/kg of intravenous Teliso-V every 2 weeks.³

The primary end point of the study is ORR per ICR.3 Secondary end points include DOR, disease control rate and progression-free survival per ICR, and OS.¹

As of the fourth interim analysis, which had a data cutoff of May 27, 2021, 136 patients had received Teliso-V, 122 of whom were evaluable for ORR. The results showed that the ORR was 36.5% (95% CI, 23.6%-51.0%) in the nonsquamous EGFR wild-type cohort, 52.2% (95% CI, 30.6%-73.2%) in the c-Met–high group, and 24.1% (95% CI, 10.3%-43.5%) in the c-Met–intermediate group. Minimal activity was seen in the nonsquamous EGFR-mutant and squamous cohorts, at 11.6% (95% CI, 3.9%-25.1%) and 11.1% (95% CI, 2.4%-29.2%), respectively.³

Regarding safety, the most common any-grade AEs were peripheral sensory neuropathy (25.0%), nausea (22.1%), and hypoalbuminemia (20.6%). Grade 5 AEs deemed potentially related to Teliso-V occurred in 2 patients with squamous disease from sudden death and pneumonitis.

"Results from the phase 2 LUMINOSITY trial mark an important step forward for AbbVie's mission to advance new oncology treatments across our ADC program targeting solid tumor types with critical patient needs," Roopal Thakkar, MD, senior vice president, development and regulatory affairs and chief medical officer at AbbVie, stated.¹

Teliso-V is also under evaluation vs docetaxel in the randomized phase 3 TeliMET NSCLC-01 trial in patients with previously treated c-Met overexpressing, EGFR wild-type nonsquamous NSCLC and in combination with osimertinib (Tagrisso) in the phase 1 M14-237 trial (NCT02099058).

References

1. AbbVie announces positive topline results from phase 2 LUMINOSITY trial evaluating telisotuzumab-vedotin (Teliso-V) for patients with previously treated non-small cell lung cancer (NSCLC). News release. AbbVie. November 29, 2023. Accessed November 29, 2023. https://news.abbvie.com/2023-11-29-AbbVie-Announces-Positive-Topline-Results-from-Phase-2-LUMINOSITY-Trial-Evaluating-Telisotuzumab-Vedotin-Teliso-V-for-Patients-with-Previously-Treated-Non-Small-Cell-Lung-Cancer-NSCLC
2. 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 November 29, 2023. https://news.abbvie.com/2022-01-04-AbbVie-Announces-U-S-FDA-Granted-Breakthrough-Therapy-Designation-BTD-to-Telisotuzumab-Vedotin-Teliso-V-for-Previously-Treated-Non-Small-Cell-Lung-Cancer
3. Camidge DR, Bar J, Horinouchi H, et al. Telisotuzumab vedotin (Teliso-V) monotherapy in patients (pts) with previously treated c-Met–overexpressing (OE) advanced non-small cell lung cancer (NSCLC). J Clin Oncol. 2022;40(suppl 16):9016. doi:10.1200/JCO.2022.40.16_suppl.9016