ALK+ advanced non-small cell lung cancer: safety and clinical activity results from a study of Alectinib plus Atezolizumab
Alectinib ( Alecensa ) has proven systemic and CNS efficacy in patients with ALK+ aNSCLC ( advanced non-small cell lung cancer ) ( ALEX trial ). T
umor cell death caused by Alectinib may release antigens broadening the potential anti-tumor T cell response.
The monoclonal antibody Atezolizumab ( Tecentriq ) releases T cell suppression by inhibiting PD-L1 binding and improves overall survival ( OS ) in second-line NSCLC treatment.
Researchers have hypothesized Atezolizumab in combination with Alectinib would lead to enhanced efficacy.
A phase Ib enrolled treatment-naïve pts with ALK+ aNSCLC regardless of PD-L1 status, including patients with untreated asymptomatic brain metastases.
Patients received Alectinib 600 mg PO BID for 7 days ( safety evaluation) , followed by Alectinib 600 mg PO BID with Atezolizumab 1200 mg IV q3w ( expansion stage ) until progression or unacceptable toxicity.
The primary objective was to evaluate the safety and tolerability of the combination. Secondary objectives included evaluation of tumor response ( ORR ) per RECIST v1.1.
At cut-off ( 18 August 2017 ) 21 patients ( safety stage n = 7; expansion stage n = 14 ) who received greater than or equal to 1 dose of Alectinib or Atezolizumab were considered safety evaluable.
Median age was 53 years.
Incidence of grade 3 and serious adverse events were 62% ( 52.4% treatment-related ) and 33%, respectively.
No grade 4–5 adverse effects were reported.
Four patients ( 19% ) discontinued Atezolizumab and 2 patients ( 10% ) discontinued Alectinib due to adverse effects.
14 patients ( 67% ) had Alectinib dose interruptions / modifications.
No dose-limiting toxicities were observed.
At a median follow up of 13 months, ( 1–22 ), ORR was 81% ( 95% CI 58.1–94.6 ); median progression-free survival was 21.7 months ( 95% CI 10.3–21.7 ), median duration of response was 20.3 months ( 95% CI 11.5–20.3 ), however, only 6 pts had progressed at the time of data cut-off.
On-treatment CD8+ T-cell increase was observed post-Alectinib run-in.
in conclusion, the combination of full dose Alectinib and Atezolizumab appears to have an acceptable safety profile with no new safety findings for either agent.
Early efficacy results are encouraging but further follow-up is needed to define the role of this combination in patients with treatment-naïve ALK+ NSCLC. ( Xagena )
Source: American Society of Clinical Oncology - ASCO Meeting, 2018
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