Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics

Figures & data

Figure 1 Capmatinib selectively targets MET on NSCLC tumor cells, inhibiting both wildtype and METex14 which lacks ubiquitination sites required for receptor degradation.

Table 1 Responses to Capmatinib by NSCLC Cohort from GEOMETRY mono-1²⁹

Cohort	MET Alteration	Previous Treatment	ORR	Median DOR (Months)
Cohort 1a (n = 69)	Amplification GCN ≥ 10	Pretreated	29%	8.3
Cohort 1b (n = 42)	Amplification GCN 6–9	Pretreated	12%	24.9
Cohort 2 (n = 54)	Amplification GCN 4–5	Pretreated	9%	9.7
Cohort 3 (n = 30)	Amplification GCN < 4	Pretreated	7%	4.2
Cohort 4 (n = 69)	METex14 any GCN	Pretreated	41%	9.7
Cohort 5a (n = 15)	Amplification GCN ≥ 10	Treatment naïve	40%	7.5
Cohort 5b (n = 28)	METex14 any GCN	Treatment naïve	68%	12.6

Notes: From Wolf J, Seto T, Han J-Y, et al. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med. 2020;383(10):944–957. Copyright © 2020 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society.²⁹

Table 2 Clinical Trials Investigating Monotherapies for METex14 NSCLC

Drug	Trial	Phase	N	Mechanism of Action	ORR for Treatment Naïve METex14 NSCLC	ORR for Pretreated METex14 NSCLC	Grade ≥ 3 TRAEs
Capmatinib^Citation29	GEOMETRY mono-1	II	364	Selective MET TKI	68%	41%	37%
Crizotinib^Citation53	PROFILE 1001	I	65	Multikinase TKI	25%	37%	29%
Tepotinib^Citation56	VISION	II	152	Selective MET TKI	44%	48%	28%
Savolitinib^Citation62	NCT02897479	II	70	Selective MET TKI	46%	40%	41%
Bozitinib^Citation64	NCT02896231	I	11	Selective MET TKI	NA	67%	27%

Wolf J, Seto T, Han J-Y, et al. Capmatinib in MET exon 14-mutated or MET-amplified non-small-cell lung cancer. N Engl J Med. 2020;383(10):944–957. doi:10.1056/NEJMoa2002787

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