Telisotuzumab Vedotin Monotherapy in Patients With Previously Treated c-Met Protein-Overexpressing Advanced Nonsquamous EGFR-Wildtype Non-Small Cell Lung Cancer in the Phase II LUMINOSITY Trial

Abstract

Purpose: Telisotuzumab vedotin (Teliso-V) is a c-Met-directed antibody-drug conjugate with a monomethyl auristatin E cytotoxic payload. The phase II LUMINOSITY trial (ClinicalTrials.gov identifier: NCT03539536) aimed to identify the optimal c-Met protein-overexpressing non-small cell lung cancer (NSCLC) population for treatment with Teliso-V (stage I) and expand the selected group for efficacy evaluation (stage II). Stage II enrolled patients with nonsquamous epidermal growth factor receptor (EGFR)-wildtype NSCLC.

Methods: Eligible patients had locally advanced/metastatic c-Met protein-overexpressing NSCLC and ≤2 previous lines of therapy (including ≤1 line of systemic chemotherapy). c-Met protein overexpression in nonsquamous EGFR-wildtype NSCLC was defined as ≥25% tumor cells with 3+ staining (high [≥50% 3+]; intermediate [≥25%-<50%]). Teliso-V was administered at 1.9 mg/kg once every 2 weeks. The primary end point was overall response rate (ORR) by independent central review.

Results: In total, 172 patients with nonsquamous EGFR-wildtype NSCLC received Teliso-V in stages I and II. ORR was 28.6% (95% CI, 21.7 to 36.2; c-Met high, 34.6% [95% CI, 24.2 to 46.2]; c-Met intermediate, 22.9% [95% CI, 14.4 to 33.4]). The median duration of response was 8.3 months (95% CI, 5.6 to 11.3; c-Met high, 9.0 [95% CI, 4.2 to 13.0]; c-Met intermediate: 7.2 [95% CI, 5.3 to 11.5]). The median overall survival was 14.5 months (95% CI, 9.9 to 16.6; c-Met high, 14.6 [95% CI, 9.2 to 25.6]; c-Met intermediate, 14.2 [95% CI, 9.6 to 16.6]). The median progression-free survival was 5.7 months (95% CI, 4.6 to 6.9; c-Met high, 5.5 [95% CI, 4.1 to 8.3]; c-Met intermediate: 6.0 [95% CI, 4.5 to 8.1]). Most common any-grade treatment-related adverse events (AEs) were peripheral sensory neuropathy (30%), peripheral edema (16%), and fatigue (14%); the most common grade ≥3 AE was peripheral sensory neuropathy (7%).

Conclusion: Teliso-V was associated with durable responses in c-Met protein-overexpressing nonsquamous EGFR-wildtype NSCLC, especially in those with high c-Met. AEs were generally manageable.

FIG 1.

Study design. The nonsquamous EGFR-wildtype cohort was expanded in stage II. A stage II China extension cohort planned to enroll up to 12 patients was added after the global stage II enrollment was complete. In addition, a supplementary cohort evaluating Teliso-V at 1.6 mg/kg q2w in up to approximately 20 patients with nonsquamous EGFR-wildtype NSCLC was added after completion of stage II enrollment. EGFR, epidermal growth factor receptor; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; MU, mutant; OE, overexpressing; q2w, once every 2 weeks; SQ, squamous; Teliso-V, telisotuzumab vedotin; WT, wildtype.

FIG 2.

Among the 172 patients in the safety analysis set for NSQ EGFR WT NSCLC at 1.9 mg/kg q2w, eight were enrolled in the China extension cohort. ^aAmong 1,954 evaluable submitted samples for prescreening patients for eligibility among those with nonsquamous EGFR-wildtype NSCLC, 23.6% were c-Met protein–overexpressing and 13.5% were c-Met high. ^bOf the 197 patients with nonsquamous EGFR-wildtype NSCLC, 53 patients were enrolled in stage I of the study. In total, 119 patients were enrolled in stage II: global enrollment, n = 111; China extension cohort, n = 8 (25 patients were enrolled in 1.6 mg/kg q2w cohort). EGFR, epidermal growth factor receptor; MU, mutated; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; OE, overexpression; q2w, once every 2 weeks; WT, wildtype.

FIG 3.

(A) Waterfall plot showing best reductions in target lesions^a; (B) time to response and duration of response for patients with a confirmed response; and (C) PFS and (D) OS for patients with c-Met protein–overexpressing, nonsquamous EGFR-wildtype NSCLC receiving 1.9 mg/kg Teliso-V. ^aOnly patients who had measurable disease at baseline and who had at least one measurable postbaseline assessment were included in the plot. DOR, duration of response; EGFR, epidermal growth factor receptor; H, c-Met high; I, c-Met intermediate; NE, not evaluable; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; Teliso-V, telisotuzumab vedotin; WT, wildtype.

FIG A1.

(A) Waterfall plot showing best reductions in target lesions for patients with c-Met protein–overexpressing, squamous NSCLC receiving 1.9 mg/kg Teliso-V^a; (B) progression-free survival for patients with c-Met protein–overexpressing, squamous NSCLC receiving 1.9 mg/kg Teliso-V; (C) OS for patients with c-Met protein–overexpressing, squamous NSCLC receiving 1.9 mg/kg Teliso-V. ^aOnly patients who had measurable disease at baseline and who had at least one measurable postbaseline assessment were included in this analysis. NSCLC, non–small cell lung cancer; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial response; SD, stable disease; SQ, squamous; Teliso-V, telisotuzumab vedotin.

FIG A2.

(A) Waterfall plot showing best reductions in target lesions^a for patients with c-Met protein–overexpressing, nonsquamous EGFR-mutant NSCLC receiving 1.9 mg/kg Teliso-V; (B) progression-free survival for patients with c-Met protein–overexpressing, nonsquamous EGFR-mutant NSCLC receiving 1.9 mg/kg Teliso-V; (C) OS for patients with c-Met protein–overexpressing, nonsquamous EGFR-mutant NSCLC receiving 1.9 mg/kg Teliso-V. ^aOnly patients who had measurable disease at baseline and who had at least one measurable postbaseline assessment were included in this analysis. EGFR, epidermal growth factor receptor; H, c-Met high; I, c-Met intermediate; MU, mutant; NSCLC, non–small cell lung cancer; NSQ, nonsquamous; OS, overall survival; PD, progressive disease; PR, partial response; SD, stable disease; Teliso-V, telisotuzumab vedotin.