Table 2 Examples of drugs targeting downstream effectors of tyrosine kinase receptors that are in clinical development

BRAF;CRAF/RTK

Sorafenib + Vinorelbine

Breast Cancer

I/II

Completed

NCT00828074

BRAF;CRAF/Microtubule/DNA replication

Sorafenib + Paclitaxel + Carboplatin

Ovarian Cancer

II

Completed

NCT00390611

Pan RAF

LY3009120

Advanced or Metastatic Cancer

I

Active

NCT02014116

Pan RAF

PLX8394

Advanced Cancers

I/II

Terminated

NCT02012231

Pan RAF

PLX8394

Advanced Unresectable Solid Tumors

I/II

Recruiting

NCT02428712

MEK1/2

Trametinib

Oral Cavity Squamous Cell Cancer

II

Completed

NCT01553851

MEK1/2

Trametinib

Cancer

II

Active

NCT01072175

MEK1/2

Dabrafenib

Papillary Thyroid Carcinoma

Unknown

Completed

NCT01534897

MEK1/2/BRAF/BRAF

Binimetinib + Encorafenib + Vemurafenib

Melanoma

III

Active

NCT01909453

MEK1/2/BRAF/EGFR

Binimetinib + Encorafenib + Cetuximab

Metastatic Colorectal Cancer

III

Recruiting

NCT02928224

MEK1/2/CDK4/6

Binimetinib + Palbociclib

NSCLC

I/II

Recruiting

NCT03170206

BRAF/EGFR

Encorafenib + Cetuximab

Metastatic Colorectal Cancer

I/II

Active

NCT01719380

BRAF

Encorafenib

Melanoma and Metastatic Colorectal Cancer

I

Active

NCT01436656

BRAF + PD-1/PD-L1 axis

Vemurafenib + Pembrolizumab

Melanoma

I

Recruiting

NCT02818023

BRAF + PD-1/PD-L1 axis

Vemurafenib + Atezolizumab

Melanoma

Active

NCT01656642

PI3K/Estrogen Receptor

Buparsilib (BKM120) + Fulvestrant

Metastatic Breast Cancer

III

Active

NCT01633060

PI3K/EGFR, HER2neu

Buparsilib (BKM120) + Lapatinib

Breast Cancer

I/II

Suspended (data analysis)

NCT01589861

PI3K

Alpelisib + Fulvestrant

Breast Cancer

III

Recruiting

NCT02437318

PI3K

Alpesilib + Fulvestrant

Breast Cancer

II

Not yet recruiting

NCT03386162

PI3K/Aromatase

Alpelisib + Fulvestrant + Letrozole

Breast Cancer

II

Recruiting

NCT03056755

PI3K/mTOR/Aromatase

Alpelisib + Everolimus + Exemestane

Breast Cancer, Kidney Cancer, Pancreatic Neuroendocrine Cancer

I

Active

NCT02077933

PI3K

Taselisib + Fulvestrant

Breast Cancer

III

Active

NCT02340221

PI3K/Aromatase

Taselisib + Letrozole

Breast Cancer

II

Completed

NCT02273973

PI3K

Taselisib

Recurrent Squamous Cell Lung Carcinoma, Stage IV Squamous Cell Lung Carcinoma

II

Active

NCT02785913

PI3K

Copanlisib (BAY80-6946)

Non-Hodgkin Lymphoma

III

Active

NCT02369016

PI3K/CD20

Copanlisib (BAY80-6946) + Rituximab

Non-Hodgkin Lymphoma

III

Recruiting

NCT02367040

PI3K

Copanlisib (BAY80-6946)

Diffuse Large B-cell Lymphoma (DLBCL)

II

Active

NCT02391116

AKT/Androgen Receptor

AZD5363 + Enzalutamide

Adenocarcinoma of the Prostate

II

Recruiting

NCT02525068

AKT/Microtubule

AZD5363 + Paclitaxel

Advanced Gastric Cancer

II

Recruiting

NCT02451956

AKT

AZD5363

Metastatic Castrate-Resistant Prostate Cancer (mCRPC)

I

Completed

NCT01692262