Table 2 Clinical trials testing the combination of a MEK inhibitor and an EGFR-TKI for the treatment of NSCLC patients

Treatment arms

Tivantinib (360 mg twice a day) + erlotinib (150 mg once a day) vs. placebo (twice a day) + erlotinib (150 mg once a day)

Tepotinib (500 mg once a day) + gefitinib (250 mg once a day) vs. pemetrexed + cisplatin/carboplatin

Capmatinib (400 mg twice a day) + gefitinib (250 mg once a day)

Onartuzumab (15 mg/kg IV) + erlotinib (150 mg once a day) vs. placebo + erlotinib (150 mg once a day)

Patients (n)

1048

55

100

499

ORR (%)

10.3 vs. 6.5

66.7 vs. 42.9^a

47^b

8.4 vs. 9.6

PFS (months)

3.6 vs. 1.9 (HR = 0.74; P < 0.001)

21.2 vs. 4.2^a

5.5^b

2.7 vs. 2.6 (HR = 0.99; P = 0.92)

OS (months)

8.5 vs. 7.8 (HR = 0.98; P = 0.81)

NA

NA

6.8 vs.9.1 (HR = 1.27; P = 0.067)

Main grade 3 or higher toxicities (over 5%)

Fatigue or asthenia (9%), dyspnea (8.8%), and anemia (6.3%) in erlotinib plus tivantinib arm vs. fatigue or asthenia (7.9%) and dyspnea (7.4%) in erlotinib plus placebo arm

51.6% in tepotinib plus gefitinib arm and 52.2% in chemotherapy arm had grade ≥ 3 TRTEAEs

Nausea (5%), peripheral edema (5%), fatigue (6%), increased amylase (6%), and increased lipase (6%)

Overall skin and subcutaneous tissue disorders (17.3), rash (7.7%), and dyspnea (5.2%) in onartuzumab plus erlotinib arm vs. overall skin and subcutaneous tissue disorders (10.7%) and rash (5.3%) in erlotinib plus placebo arm