Telisotuzumab Vedotin Elicits Compelling Data in EGFR-Mutant, c-Met NSCLC

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Telisotuzumab vedotin (ABBV-399) generated an encouraging overall response rate (ORR) per independent central review (ICR) of 35% and 23% across c-Met-high and c-Met-intermediate patients with epidermal growth factor receptor (EGFR) wild-type, advanced/metastatic nonsquamous non–small cell lung cancer (NSCLC),according to topline results from the phase 2 LUMINOSITY trial (NCT03539536).¹

Among patients with c-Met-high and c-Met-intermediate EGFR-mutated NSCLC, the median duration of response (DOR) per ICR was 9 months and 7.2 months, and the median overall survival (OS) was 14.6 months and 14.2 months, respectively.

For safety, no new safety signals were observed with telisotuzumab vedotin, and the safety profile of the agent was consistent with previous findings. As a monotherapy, telisotuzumab vedotin was generally well managed and well tolerated. Full data from the LUMINOSITY trial are expected to be presented at an upcoming medical meeting and discussed with global health authorities.

"Two categories of MET+ both show good response rates, suggesting the ongoing docetaxel vs telisotuzumab vedotin phase 3 trial still makes sense," Ross Camidge, MD, PhD, University of Colorado Cancer Center, United States, and principal investigator for the trial, told Targeted Oncology^TM "This was in EGFR wild-type, nonsquamous NSCLC. The development in EGFR-mutant in combination with osimertinib [Tagrisso] is a separate approach still being explored."

About the Phase 2 LUMINOSITY Trial

LUMINOSITY is an ongoing, open-label, phase 2 study designed evaluate the efficacy and safety of telisotuzumab vedotin in the second-line or third-line setting for patients with advanced/metastatic EGFR wild-type, nonsquamous NSCLC with high levels of c-Met overexpression.²

The trial enrolled 270 patients with locally advanced or metastatic NSCLC who have c-Met-positive disease, histologically documented non-squamous EGFR wild-type NSCLC, and received no more than 2 lines of prior systemic therapy in the locally advanced or metastatic setting. Multiple lines of tyrosine kinase inhibitors targeting the same tyrosine kinase count as 1 line of therapy, according to these eligibility criteria. Patients must also have progressed on systemic cytotoxic therapy, have an ECOG performance status of 0 to 1, and metastases to the central nervous system are only eligible after definitive therapy, including surgery or radiotherapy.²

Investigators are evaluating the primary end point of ORR along with secondary end points of DOR, disease control rate, progression-free survival, and OS.

"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," said Roopal Thakkar, MD, senior vice president, development and regulatory affairs and chief medical officer of AbbVie, in a press release.¹

About Telisotuzumab Vedotin

Telisotuzumab vedotin is an antibody-drug conjugate (ADC) which targets c-Met, a receptor tyrosine kinase that is overexpressed in NSCLC tumors. The FDA granted the agent a breakthrough therapy designation in January 2023 for patients with advanced/metastatic EGFR wild-type, nonsquamous NSCLC with high levels of c-Met overexpression whose disease progressed on or after platinum-based therapy.

In addition to LUMINOSITY, telisotuzumab vedotin is being evaluated as a monotherapy in patients with previously treated c-Met overexpressing EGFR wild-type nonsquamous NSCLC in the randomized phase 3 study TeliMET NSCLC-01. This trial is currently enrolling patients and has an estimated study completion date of March 2028.³

"The recent data of AZ/DAICHIIS Trop2 ADC vs docetaxel is encouraging for the ADC space, but there were concerns re toxicity of the trop 2 agents. These teliso-V data open up the idea that different ADCs, sometimes involving prescreening and enrichment, if the efficacy increases and/or the toxicity decreases compared to Trop 2 approaches still have much to contribute," added Camidge.

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://tinyurl.com/268wz8yw

2. Study of telisotuzumab vedotin (ABBV-399) in participants with previously treated c-Met+ non-small cell lung cancer. ClinicalTrials.gov. Updated July 14, 2023. Accessed November 29, 2023. https://clinicaltrials.gov/study/NCT03539536

3. A study to assess disease activity and adverse events of intravenous (IV) telisotuzumab vedotin compared to IV docetaxel in adult participants with previously treated non-squamous non-small cell lung cancer (NSCLC). ClinicalTrials.gov. Updated November 27, 2023. Accessed November 29, 2023. https://www.clinicaltrials.gov/study/NCT04928846