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In Pursuit of the Next Big Thing for Second-Line Treatment in Advanced NSCLC

– It's time to move beyond chemoIO, experts say; will an ADC own the future?


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Outside of pediatrics, it's a safe bet that scribbled smiley faces don't have a huge role to play when lung cancer specialists communicate with their patients about non-small cell lung cancer (NSCLC) therapeutic options. But that's exactly what Giannis Mountzios, MD, PhD, of the Henry Dunant Hospital Center in Athens, Greece, and colleagues, reported that they used: "Our strategy for explaining immunotherapy toxicity involves two main components: a hand-drawn diagram that the patient takes home with them and the verbal explanation of what those outcomes look like for the patient and their cancer treatment," the team wrote in a review in the .

"Together, the tool presents the categorical risk of side effects, gives a common example with a verbal story, and includes the time course, the implications for future treatment, and uses an adapted faces scale. Faces scales are easy to use and interpret nonverbally, are reliable and cross cultural, and can be understood by those with cognitive impairment," Mountzios and co-authors explained.

Their description of this communication method was part of a general overview on moving beyond chemoimmunotherapy (aid) in advanced NSCLC. Of course, the authors conceded that chemoIO is "currently the preferred first-line treatment option" for most patients with advanced NSCLC sans driver genetic alterations. "Most of these patients, however, will experience disease progression within the first year after treatment initiation and both patients and their physicians will be confronted with the dilemma of the optimal second-line treatment," the team said.

One of the second-line options that Mountzios' group highlighted was telisotuzumab vedotin (Teliso-V), "a novel ADC [antibody-drug conjugate] directed against MET-amplified and c-Met-overexpressing tumors, which has shown enhanced activity in the subgroup of patients with nonsquamous, EGFR wild-type [WT]," per the phase II trial that was recently updated in the , with overall response rates of 34.6% for patients with high c-Met expression and 22.9% for patients with c-Met-intermediate expression.

In that update, D. Ross Camidge, MD, PhD, of the University of Colorado Cancer Center in Aurora, and colleagues reported that the adverse events (AEs) with Teliso-V were manageable. The most common any-grade treatment-related AEs in LUMINOSITY were peripheral sensory neuropathy, peripheral edema, and fatigue; the most common grade ≥3 AE was peripheral sensory neuropathy. There were also a handful of cases of interstitial lung disease (ILD), and Camidge's group pointed out that "most patients with nonsquamous EGFR-WT NSCLC in the current study received a previous immune checkpoint inhibitor, and a previous report has suggested that patients with previous immune checkpoint inhibitor therapy have a greater likelihood of ILD during subsequent therapy."

LUMINOSITY co-investigator Shun Lu, MD, PhD, of Shanghai Jiao Tong University, is involved in the ongoing TeliMET NSCLC-01 trial. The open-label, global phase III trial evaluating the efficacy, safety, pharmacokinetics, and pharmacodynamics of Teliso-V monotherapy compared with docetaxel in patients with locally advanced/metastatic c-Met overexpressing EGFR WT nonsquamous NSCLC who have progressed on prior therapy. The trial has an estimated completion date of March 2028.

Barrett Ainsworth, PhD, scientific director of oncology clinical development at AbbVie, shared highlights from the recent "trial in progress" poster at the 2024 ASCO annual meeting.

What is the background for TeliMET NSCLC-01?

Ainsworth: Teliso-V is a first-in-class ADC. C-met is overexpressed in a subset of patients with NSCLC. In the primary analysis of LUMINOSITY, the median duration of response [DoR] for the overall C-met-expressing population was 8.3 months and 9 months in C-met high [with Teliso-V monotherapy] patients. The median overall survival [OS] was 14.5 months overall and 14.6 months in C-met high patients.

What are some of the TeliMET trial details?

Ainsworth: Patients are randomized 1:1 to either Teliso-V or docetaxel and treated until disease progression, toxicity, or other discontinuation criteria are met. Stratification factors include C-met high status, prior immune checkpoint inhibitor therapy, and region -- i.e., U.S./Canada, Europe, Pan-Asia, and rest of the world.

Approximately 698 patients will be enrolled, with Teliso-V dosed at 1.9 mg/kg every 2 weeks as an IV infusion. Docetaxel will be dosed at 75 mg/m2 every 3 weeks, or according to local package insert recommendations.

Patients must have C-met overexpressing NSCLC per central immunohistochemistry. They must have also progressed on at least one prior line of therapy, which can include no more than one prior line of platinum-based chemotherapy. Patients must not have actionable activating EGFR mutations. Patients receiving prior C-met-targeted antibody therapy or prior docetaxel therapy are excluded.

The co-primary endpoints are progression-free survival [PFS] per independent central review [ICR] and OS. Secondary endpoints include confirmed ORR by ICR, DoR by ICR, patient-reported outcome, a PFS per investigator assessment.

What's the current trial status?

Ainsworth: Enrollment for the ongoing TeliMET NSCLC-01 trial began in March 2022, with 250 sites in 34 countries planned.

Read the review article by Mountzios and colleagues here.

Mountzios disclosed financial relationships with Roche, Boehringer Ingelheim, AstraZeneca, MSD, Bristol Myers Squibb GmbH, Novartis, Amgen, Takeda, AstraZeneca/Greece, Novartis, Ipsen, and Demo Pharmaceutical.

TeliMET NSCLC-01 is funded by AbbVie; Ainsworth and some co-authors of the study are company employees.

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