J Clin Oncol: Telisotuzumab Vedotin in combination with erlotinib for the treatment of c-Met-mutated NSCLC

C-Met protein overexpression and epidermal growth factor receptor (EGFR) mutations can occur simultaneously in non-small cell lung cancer (NSCLC), providing a strong theoretical basis
for dual-targeted therapy.
Telisotuzumab vedotin (Teliso-V) is the first antibody-drug conjugate targeting c-Met, which has shown a tolerable safety profile and antitumor activity
as monotherapy.

The study was designed to evaluate the initial activity and safety
of Teliso-V in combination with erlotinib (an EGFR tyrosine kinase inhibitor) in patients with c-Met-positive (+)NSCLC.

Patients aged 18 years or older with c-Met(+) NSCLC were treated
with Teliso-V (2.
7 mg/kg once on 21 days) + erlotinib (150 mg/day).
Patients
with EGFR-activating mutation (EGFR M+) who had progressed after prior EGFR TKI therapy were subsequently recruited and requested.
Primary endpoints included safety, pharmacokinetics, objective response rate (ORR), and progression-free survival (PFS).

Progression-free survival rates in patients with different mutation states in each group

As of January 2020, a total of 42 patients (36 of whom could be evaluated for efficacy)
had been enrolled.
Neuropathy was the most common reported adverse event of any grade, with 24 (57%) of 42 patients experiencing at least one adverse event
.
The pharmacokinetic profile of Teliso-V in combination with erlotinib is similar
to that of Teliso-V monotherapy.
The median PFS for all patients assessed for all efficacy was 5.
9 months (95% CI 2.
8 - not achieved).

The ORR of EGFR-M+ patients (n=28) was 32.
1%.

Among EGFR-M+ patients, the ORR for patients with high c-Met (n=15) was 52.
6%.

For patients with non-T790M+ and T790M status unknown, the median PFS was 6.
8 months, compared with 3.
7 months
for T790M+ patients.

In summary, Teliso-V combined with erlotinib showed encouraging antitumor activity and acceptable toxicity
in patients with EGFR and c-Met mutations in NSCLC.

Original source:

D.
Ross Camidge, et al.
Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein–Expressing Non–Small-Cell Lung Cancer.
Journal of Clinical Oncology.
October 26, 2022.
https://ascopubs.
org/doi/full/10.
1200/JCO.
22.
00739