Phase Ib Study of Telisotuzumab Vedotin in Combination With Erlotinib in Patients With c-Met Protein-Expressing Non-Small-Cell Lung Cancer

  • J Clin Oncol. 2023 Feb 10;41(5):1105-1115. doi: 10.1200/JCO.22.00739.
D Ross Camidge  1 ,  Fabrice Barlesi  2  3 ,  Jonathan W Goldman  4 ,  Daniel Morgensztern  5 ,  Rebecca Heist  6 ,  Everett Vokes  7 ,  Alex Spira  8 ,  Eric Angevin  9 ,  Wu-Chou Su  10 ,  David S Hong  11 ,  John H Strickler  12 ,  Monica Motwani  13 ,  Martin Dunbar  13 ,  Apurvasena Parikh  14 ,  Elysa Noon  13 ,  Vincent Blot  13 ,  Jun Wu  13 ,  Karen Kelly  15
Affiliations
  • 1. University of Colorado Cancer Center, Aurora, CO.
  • 2. Multidisciplinary Oncology and Therapeutic Innovations Department, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Inserm U911 CRO2, Marseille, France.
  • 3. Medical Oncology Department, Gustave Roussy, Villejuif, France.
  • 4. David Geffen School of Medicine at UCLA, Los Angeles, CA.
  • 5. Washington University School of Medicine, St Louis, MO.
  • 6. Massachusetts General Hospital Cancer Center, Boston, MA.
  • 7. University of Chicago Medicine, Chicago, IL.
  • 8. Virginia Cancer Specialists Research Institute, Fairfax, VA.
  • 9. Drug Development Department (DITEP), Gustave Roussy, Villejuif, France.
  • 10. National Cheng Kung University Hospital, Tainan, Taiwan.
  • 11. The University of Texas MD Anderson Cancer Center, Houston, TX.
  • 12. Duke University Medical Center, Durham, NC.
  • 13. AbbVie Inc, North Chicago, IL.
  • 14. AbbVie Inc, Redwood City, CA.
  • 15. University of California Davis Comprehensive Cancer Center, Sacramento, CA.
PMID: 36288547 DOI: 10.1200/JCO.22.00739
Abstract

Purpose: Overexpression of c-Met protein and epidermal growth factor receptor (EGFR) mutations can co-occur in non-small-cell lung Cancer (NSCLC), providing strong rationale for dual targeting. Telisotuzumab vedotin (Teliso-V), a first-in-class antibody-drug conjugate targeting c-Met, has shown a tolerable safety profile and antitumor activity as monotherapy. Herein, we report the results of a phase Ib study (ClinicalTrials.gov identifier: NCT02099058) evaluating Teliso-V plus erlotinib, an EGFR tyrosine kinase inhibitor (TKI), in patients with c-Met-positive (+) NSCLC.

Patients and methods: This study evaluated Teliso-V (2.7 mg/kg once every 21 days) plus erlotinib (150 mg once daily) in adult patients (age ≥ 18 years) with c-Met+ NSCLC. Later enrollment required presence of an EGFR-activating mutation (EGFR-M+) and progression on a prior EGFR TKI. End points included safety, pharmacokinetics, objective response rate (ORR), and progression-free survival (PFS). The efficacy-evaluable population consisted of c-Met+ patients (confirmed histology [H]-score ≥ 150) who had at least one postbaseline scan; c-Met+ patients with H-scores ≥ 225 were classified as c-Met high.

Results: As of January 2020, 42 patients were enrolled (N = 36 efficacy-evaluable). Neuropathies were the most common any-grade adverse events reported, with 24 of 42 patients (57%) experiencing at least one event. The pharmacokinetic profile of Teliso-V plus erlotinib was similar to Teliso-V monotherapy. Median PFS for all efficacy-evaluable patients was 5.9 months (95% CI, 2.8 to not reached). ORR for EGFR-M+ patients (n = 28) was 32.1%. Of EGFR-M+ patients, those who were c-Met high (n = 15) had an ORR of 52.6%. Median PFS was 6.8 months for non-T790M+ and for those whose T790M status was unknown, versus 3.7 months for T790M+.

Conclusion: Teliso-V plus erlotinib showed encouraging antitumor activity and acceptable toxicity in EGFR TKI-pretreated patients with EGFR-M+, c-Met+ NSCLC.

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