medwireNews: Phase 1b trial findings indicate that telisotuzumab vedotin (teliso-v), given in combination with erlotinib, may have potential as a treatment option for progressing EGFR mutation-positive non-small-cell lung cancer (NSCLC) with c-Met overexpression.
“Teliso-V plus erlotinib showed encouraging antitumor activity and acceptable toxicity” in patients who had previously been treated with an EGFR–tyrosine kinase inhibitor (TKI), report Ross Camidge (University of Colorado Cancer Center, Aurora, USA) and co-workers.
Of the 42 adults in the study assigned to receive the Met-targeted antibody–drug conjugate teliso-v 2.7 mg/kg every 21 days plus erlotinib 150 mg/day, 36 had evaluable disease; 28 had disease positive for c-Met overexpression, a MET exon 14 skipping mutation, or MET amplification, as well as for EGFR mutations. Five were positive for C-Met overexpression only, and three had NSCLC positive for both c-Met overexpression and either a rare or unknown EGFR mutation.
The majority (69%) had previously received at least three lines of treatment and 83% had been given a first- or second-generation EGFR–TKI, while 44% had received a third-generation agent as their last therapy, the team reports in the Journal of Clinical Oncology.
The patients received teliso-v and erlotinib for a median of 18.1 and 20.3 weeks, respectively.
All 42 participants experienced at least one any-grade adverse event (AE) on treatment, most commonly peripheral sensory neuropathy (43%), dermatitis acneiform (38%), diarrhea (33%), and hypoalbuminemia (33%).
Furthermore, 64% had one or more grade 3 or more severe AE, such as pulmonary embolism (14%) and hypokalemia (10%), while 7% of patients each had peripheral sensory neuropathy, diarrhea, disease progression, and hypophosphatemia. One patient died from hemoptysis possibly related to teliso-v therapy.
Overall, 30.6% of evaluable participants achieved an objective response to treatment, and the disease control rate (DCR) was 86.1%. The median progression-free survival (PFS) was 5.9 months and median duration of response was not reached at data cutoff.
Among the 28 EGFR mutation-positive participants the objective response rate was 32.1%, DCR was 85.7% and the median PFS was 5.9 months, while exploratory analysis suggested comparable rates of objective response in patients with the EGFR T790M mutation and those with other types of EGFR mutations (31 vs 33%) but a lower median duration of PFS (3.7 vs 6.8 months).
The 15 EGFR mutation-positive patients who were given osimertinib had poorer responses to the study regimen than the 13 who did not receive the third-generation EGFR–TKI, in terms of both objective response (26.7 vs 38.5%) and disease control (73.3 vs 100%).
In addition, patients with high histology c-Met scores (≥225) were more likely to achieve an objective response than those with lower scores (52.6 vs 12.5%) but had a similar DCR (78.9 vs 87.5%). Five of the six patients with MET amplification were also c-Met-high; 60.0% achieved an objective response and 100% disease control.
“Although exploratory, targeting c-Met and EGFR showed promising results in this underserved patient population and is worthy of further evaluation in larger studies,” write Camidge et al.
“Our data also support additional prospective investigations of [teliso-v] in combination with osimertinib in selected patient populations.”
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