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Capmatinib in patients with METex14-mutated advanced non-small cell lung cancer who received prior immunotherapy: GEOMETRY mono-1 study


MET exon 14 skipping mutations ( METex14 ) are seen in 3-4% of patients with non-small cell lung cancer ( METex14 NSCLC ) and are associated with poor outcomes.

In the phase 2 GEOMETRY mono-1 study, Capmatinib ( Tabrecta ) was efficacious in patients with METex14 NSCLC who were treatment-naive ( overall response rate [ ORR ] 68% ) or received one/two lines of therapy ( ORR 41% ).

A post-hoc analysis evaluating efficacy and safety of Capmatinib in patients with METex14 NSCLC who received immunotherapy before study entry, was presented.

Cohort 4 ( pre-treated METex14 NSCLC ) is included in this analysis.
Efficacy ( ORR and progression-free survival [ PFS ] ) on prior immunotherapy, determined by the investigator is reported.
Efficacy (ORR, duration of response [ DOR ] and PFS by blinded independent review committee ( BIRC ) per RECIST 1.1 ) of Capmatinib 400 mg BID are reported for patients with or without prior immunotherapy, as well as safety and biomarker status.

As of 28 October 2019, 69 patients with METex14 NSCLC were enrolled.
Of these, 19 had prior immunotherapy ( median age 71 years; women 63.2%; never smokers 63.2% ) and 50 did not ( median age 71.5 years; women 56%; never smokers 56% ).
Of 19 patients with prior immunotherapy, 9 received immunotherapy first-line and 10 second-line, 18/19 received immunotherapy as monotherapy.

14 patients of 19 did not respond to immunotherapy ( 8 of 19 had progressive disease as best overall response ).

Median progression-free survival on prior immunotherapy was 3.29 months ( 95%CI 2.10-5.16 ).

Efficacy of Capmatinib was demonstrated in patients who received and who did not receive prior immunotherapy: ORR 57.9% ( n=11/19; 95%CI 33.5-79.7 ) and 34% ( n=17/50; 95%CI 21.2-48.8 ); median DOR 11.20 months ( 95%CI 3.35-NE ) and 7.16 months ( 95%CI 4.17-11.14 ), respectively.

Durable responses were observed in patients with lack of response / primary resistance to immunotherapy.

Safety findings with Capmatinib for patients with prior immunotherapy were similar to patients without prior immunotherapy.
No increased risk of interstitial lung disease / pneumonitis was observed.

Average tumor mutation burden was less than 10 mut/mb in both groups.

In conclusion, efficacy data of immunotherapy in patients with METex14 NSCLC is limited.
Capmatinib has demonstrated efficacy irrespective of the prior treatment with immunotherapy, including in patients with lack of response / primary resistance to immunotherapy.
Capmatinib was well-tolerated in post-immunotherapy patients. ( Xagena )

Source: European Society for Medical Oncology ( ESMO ) Virtual Meeting, 2020

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