JTO Clinical and Research Reports (Aug 2022)

Brief Report: Safety and Antitumor Activity of Alectinib Plus Atezolizumab From a Phase 1b Study in Advanced ALK-Positive NSCLC

  • Dong-Wan Kim, MD, PhD,
  • Shirish Gadgeel, MD,
  • Scott N. Gettinger, MD,
  • Gregory J. Riely, MD, PhD,
  • Geoffrey R. Oxnard, MD,
  • Tarek Mekhail, MD,
  • Peter Schmid, MD, PhD,
  • Afshin Dowlati, MD,
  • Rebecca S. Heist, MD, MPH,
  • Antoinette J. Wozniak, MD,
  • Jatinder Singh, PhD,
  • Edward Cha, MD, PhD,
  • Jessica Spahn, PhD,
  • Sai-Hong Ignatius Ou, MD, PhD

Journal volume & issue
Vol. 3, no. 8
p. 100367

Abstract

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Introduction: Alectinib is a preferred first-line treatment option for advanced ALK-positive NSCLC. Combination regimens of alectinib with immune checkpoint inhibitors are being evaluated for synergistic effects. Methods: Adults with treatment-naive, stage IIIB/IV, or recurrent ALK-positive NSCLC were enrolled into a two-stage phase 1b study. Patients received alectinib 600 mg (twice daily during cycle 1 and throughout each 21-d cycle thereafter) plus atezolizumab 1200 mg (d8 of cycle 1 and then d1 of each 21-d cycle). Primary objectives were to evaluate safety and tolerability of alectinib plus atezolizumab. Secondary objectives included assessments of antitumor activity. Results: In total, 21 patients received more than or equal to 1 dose of alectinib or atezolizumab. As no dose-limiting toxicities were observed in stage 1 (n = 7), the starting dose and schedule were continued into stage 2 (n = 14). Median duration of follow-up was 29 months (range: 1–39). Grade 3 treatment-related adverse events occurred in 57% of the patients, most often rash (19%). No grade 4 or 5 treatment-related adverse events were reported. Confirmed objective response rate was 86% (18 of 21; 95% confidence interval [CI]: 64–97). Median progression-free survival was not estimable (NE) (95% CI: 13 mo–NE), neither was median overall survival (95% CI: 33 mo–NE). Conclusions: The combination of alectinib and atezolizumab is feasible, but increased toxicity was found compared with the individual agents. With small sample sizes and relatively short follow-up, definitive conclusions regarding antitumor activity cannot be made.

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