In a phase Ib trial reported in the Journal of Clinical Oncology, D. Ross Camidge, MD, PhD, and colleagues found that the combination of telisotuzumab vedotin and erlotinib showed activity in c-Met protein–expressing advanced non–small cell lung cancer (NSCLC), including those with an EGFR mutation and prior EGFR tyrosine kinase inhibitor treatment.

D. Ross Camidge, MD, PhD

As stated by the investigators, “Overexpression of c-Met protein and … EGFR mutations can co-occur in … NSCLC, providing strong rationale for dual targeting. Telisotuzumab vedotin, … a first-in-class antibody-drug conjugate targeting c-Met, has shown a tolerable safety profile and antitumor activity as monotherapy.”

Study Details

In the international multicenter study, 42 patients with c-Met–positive disease were enrolled between April 2015 and January 2020; later enrollment was restricted to patients who also had an EGFR-activating mutation and disease progression on a prior EGFR tyrosine kinase inhibitor. Patients received telisotuzumab vedotin at 2.7 mg/kg once every 21 days plus erlotinib at 150 mg once daily.

A total of 36 patents were evaluable for efficacy, including 26 with an EGFR mutation. The efficacy-evaluable population consisted of those patients with a confirmed histology (H)-score ≥ 150 who had at least one postbaseline scan; c-Met–positive patients with H-scores ≥ 225 were classified as c-Met high.

Responses

Among all 36 evaluable patients, an objective response was observed in 11 (30.6%, 95% confidence interval [CI] = 16.3%–48.1%) and the disease control rate was 86.1%. Median duration of response was not reached. Median progression-free survival was 5.9 months (95% CI = 2.8 months to not reached).

Among the 28 patients with an EGFR mutation and prior tyrosine kinase inhibitor treatment, objective response was observed in 9 (32.1%, 95% CI = 15.9%–52.4%) and the disease control rate was 85.7%. Median progression-free survival was 5.9 months (95% CI = 2.8 months to not reached).

Among 15 patients with an EGFR mutation with c-Met–high status, the objective response rate was 52.6%. Median progression-free survival was 6.8 months among 15 patients with non-T790M mutations or whose T790M status was unknown, compared with 3.7 months among 13 patients with a T790M mutation.

Toxicity

Among the 42 patients in the safety population, the most common adverse events of any grade were peripheral sensory neuropathy (43%), dermatitis acneiform (38%), diarrhea (33%), and hypoalbuminemia (33%). The most common events considered related to telisotuzumab vedotin were peripheral sensory neuropathy (36%) and peripheral neuropathy (19%).

Grade ≥ 3 adverse events occurred in 64% of patients, most commonly pulmonary embolism (14%); hypokalemia (10%); and diarrhea, malignant neoplasm progression, peripheral sensory neuropathy, and hypophosphatemia (7% each). Treatment-related grade ≥ 3 adverse events occurred in 31%, most commonly hypophosphatemia and peripheral sensory neuropathy (7% each). Death in 1 patient, due to hemoptysis, was considered potentially related to telisotuzumab vedotin.

The investigators concluded: “[Telisotuzumab vedotin] plus erlotinib showed encouraging antitumor activity and acceptable toxicity in EGFR [tyrosine kinase inhibitor] pretreated patients with [EGFR-mutant, c-Met–positive] NSCLC.”

Ross Camidge, MD, PhD, of the University of Colorado Cancer Center, Aurora, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by AbbVie, Inc. For full disclosures of the study authors, visit ascopubs.org.