Supplementary Table 1: Clinical trials of combination of MEK inhibitors and immunotherapies in NSCLC.

(1)

Supplementary Table 1: Clinical trials of combination of MEK inhibitors and immunotherapies in NSCLC.

NCT number Title Conditions Interventions Phase Status

NCT03299088 Pembrolizumab and Trametinib in Treating Patients With Stage IV Non-Small Cell Lung Cancer and KRAS Gene Mutations

(1) KRAS Gene Mutation

(2) Metastatic Non-Squamous Non- Small Cell Lung Carcinoma (3) Recurrent Non-Squamous Non-

Small Cell Lung Carcinoma (4) Stage IV Non-Small Cell Lung

Cancer AJCC v7

Biological:

Pembrolizumab Drug: Trametinib

I Recruiting

NCT03225664 Trametinib and Pembrolizumab in Treating Patients With Recurrent Non-small Cell Lung Cancer That Is Metastatic, Unresectable, or Locally Advanced

(1) Metastatic Lung Non-Small Cell Carcinoma

(2) Recurrent Lung Non-Small Cell Carcinoma

(3) Stage III Lung Cancer AJCC v8 (4) Stage IIIA Lung Cancer AJCC v8 (5) Stage IIIB Lung Cancer AJCC v8 (6) Stage IIIC Lung Cancer AJCC v8 (7) Stage IV Lung Cancer AJCC v8 (8) Stage IVA Lung Cancer AJCC v8 (9) Stage IVB Lung Cancer AJCC v8 (10) Unresectable Lung Non-Small Cell

Carcinoma

Biological:

Pembrolizumab

Other: Pharmacokinetic Study

Drug: Trametinib

I/II Recruiting

NCT03581487 Durvalumab, Tremelimumab, and Selumetinib in Treating Participants With Recurrent or Stage IV Non-small Cell Lung Cancer

(2) Stage IV Lung Cancer AJCC v8

Biological: Durvalumab Drug: Selumetinib

I/II Recruiting

(2)

(3) Stage IVA Lung Cancer AJCC v8 (4) Stage IVB Lung Cancer AJCC v8

Biological:

Tremelimumab NCT02179671 Immune-Modulated Study of Selected Small

Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) in Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer (Experimental: Selumetinib+Docetaxel with a Seq. Switch to a MEDI4736)

Locally Advanced or Metastatic Non- Small-Cell Lung Cancer (Stage IIIB-IV)

Drug:

Selumetinib+Docetaxel Drug: Tremelimumab

II Completed

NCT03178552 A Study to Evaluate Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (Cohort E: Atezolizumab, Vemurafenib, and Cobimetinib)

Non-Small Cell Lung Cancer Drug: Atezolizumab Drug: Cobimetinib Drug: Vemurafenib

II/III Recruiting

NCT03337698 A Study Of Multiple Immunotherapy-Based Treatment Combinations In Participants With Metastatic Non-Small Cell Lung Cancer

(Morpheus- Non-Small Cell Lung Cancer) (Stage 1:

Cohort 1 and 2: Atezolizumab + Cobimetinib)

Carcinoma, Non-Small-Cell Lung Drug: Atezolizumab Drug: Cobimetinib

I/II Recruiting

NCT03600701 Atezolizumab and Cobimetinib in Treating Patients With Metastatic, Recurrent, or Refractory Non- small Cell Lung Cancer

(2) Refractory Lung Non-Small Cell Carcinoma

(3) Stage IV Lung Non-Small Cell Cancer AJCC v7

Drug: Atezolizumab Drug: Cobimetinib

II Recruiting

(3)

NCT02586987 A Study to Assess the Safety, Tolerability and Anti- tumour Activity of Ascending Doses of Selumetinib in Combination With MEDI4736 and Selumetinib in Combination With MEDI4736 and

Tremelimumab in Patients With Advanced Solid Tumours

(1) Lung Cancer

(2) Others (Melanoma, Head and Neck Carcinoma, Gastroesophageal Cancer, Breast Cancer, Pancreatic Adenocarcinoma, Colorectal Cancer, Biliary Tract Cancer)

Drug: Selumetinib Drug: MEDI4736 Drug: Tremelimumab

I Completed

NCT03833427 Study of Selumetinib in Combination With Pembrolizumab in Participants With

Advanced/Metastatic Solid Tumors (MK-5618-001)

Advanced/Metastatic Solid Tumors Drug: Selumetinib Biological:

Pembrolizumab

I Recruiting

NCT03264066 A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants With Solid Tumors

Solid Tumors Drug: Cobimetinib

Drug: Atezolizumab

II Active, not recruiting NCT01988896 Study of Atezolizumab in Combination With

Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors

Solid Tumors Drug: Atezolizumab

Drug: Cobimetinib

I Completed

NCT01928394 A Study of Nivolumab by Itself or Nivolumab Combined With Ipilimumab in Patients With Advanced or Metastatic Solid Tumors (Arm N-I, Level 2d: Nivolumab+Ipilimumab+Cobimetinib)

Advanced or Metastatic Solid Tumors Biological: Nivolumab Biological: Ipilimumab Drug: Cobimetinib

I/II Active, not recruiting

NSCLC: Non-small cell lung cancer; MEK: Mitogen-activated protein kinase kinase; AJCC: American Joint Committee Cancer; AZD9291:

Osimertinib; MEDI4736: Durvalumab; AZD6244: Selumetinib.