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Table 1 Clinical trials targeting KRAS

From: Oncogenic KRAS blockade therapy: renewed enthusiasm and persistent challenges

Target

Agent

Combinations

Study

phase

Tumor type

Recruitment status

Trial number

BRAF, CRAF

LXH-254

None

I

Advanced solid tumors harboring MAPK pathway alterations

Active, not recruiting

NCT02607813

BRAF, CRAF

LXH-254

Rineterkib (RAF/ERK inhibitor); trametinib (MEK inhibitor); ribociclib (CDK4/6 inhibitor); EGF816 (EGFR inhibitor); dabrafenib (BRAF mutant inhibitor)

I, II

Unresectable or metastatic melanoma; EGFR-mutant NSCLC

Recruiting; active, not recruiting

NCT04417621; NCT02974725; NCT03333343; NCT04294160

ERK

LY3214996; GDC-0994; ulixertinib; MK-8353

None

I, II

Acute myeloid leukemia; locally advanced or metastatic solid tumors; metastatic uveal melanoma; acute myelogenous leukemia or myelodysplastic syndromes

Recruiting; completed; terminated

NCT04081259; NCT01875705; NCT04488003; NCT03417739; NCT02296242; NCT01358331

ERK

LY3214996

RMC-4630 (SHP2-inhibitor); abemaciclib (CDK4/6 inhibitor); hydroxychloroquine (autophagy inhibitor)

I, II

Metastatic KRAS mutant cancers; solid tumors harboring pathogenic alterations in BRAF, RAF1, MEK1/2, ERK1/2, and NF1

Not yet recruiting

NCT04916236; NCT04956640; NCT04534283; NCT04616183; NCT04391595; NCT04386057

ERK

GDC-0994

Cobimetinib (MEK inhibitor)

I

Locally advanced or metastatic solid tumors

Completed

NCT02457793

ERK

Ulixertinib

Hydroxychloroquine (autophagy inhibitor); palbociclib (CDK4/6 inhibitor)

I, II

Advanced MAPK-mutated gastrointestinal adenocarcinomas; advanced pancreatic and other solid tumors

Recruiting

NCT041452973; NCT03454035

ERK

MK-8353

Selumetinib (MEK inhibitor); pembrolizumab (anti–PD-1 ab)

I

Advanced malignancies

Completed; active, not recruiting

NCT03745989; NCT02972034

KRAS

AZD4785

None

I

Advanced solid tumors

Completed

NCT03101839

KRAS-G12C

Sotorasib

None

I, II

KRAS-G12C–mutant advanced/metastatic solid tumors

Recruiting; not yet recruiting

NCT04380753; NCT04625647; NCT04667234; NCT04933695

KRAS-G12C

Sotorasib

Docetaxel (microtubule inhibitor); pembrolizumab (anti–PD-1 ab)

I, II, III

KRAS-G12C–mutant advanced/metastatic solid tumors

Active, not recruiting; recruiting

NCT04303780; NCT03600883; NCT04613596

KRAS-G12C

Adagrasib

Docetaxel (microtubule inhibitor); pembrolizumab (anti–PD-1 ab); cetuximab (anti-EGFR ab); afatinib (pan-EGFR inhibitor); TNO155 (SHP2 inhibitor)

I, II, III

KRAS-G12C–mutant advanced/metastatic solid tumors

Recruiting

NCT04685135; NCT03785249; NCT04330664; NCT04793958

KRAS-G12C

GDC-6036

Atezolizumab (anti–PD-L1 ab); cetuximab (anti-EGFR ab); bevacizumab (anti-VEGF ab); erlotinib (EGFR inhibitor)

I

KRAS-G12C–mutant advanced/metastatic solid tumors

Recruiting

NCT04449874

KRAS-G12C

D-1553

Standard treatment

I

KRAS-G12C–mutant advanced/metastatic solid tumors

Recruiting

NCT04585035

KRAS-G12C

JNJ-74699157

Standard treatment

I

KRAS-G12C–mutant advanced/metastatic solid tumors

Completed

NCT04006301

KRAS-G12C

LY3499446

Abemaciclib (CDK4/6 inhibitor); cetuximab (anti-EGFR ab); erlotinib (EGFR inhibitor); docetaxel (microtubule inhibitor)

I, II

KRAS-G12C–mutant advanced/metastatic solid tumors

Terminated

NCT04165031

KRAS-G12D

siG12D-LODER

Gemcitabine + nab-paclitaxel; FOLFIRINOX

II

Advanced pancreatic cancer

Recruiting

NCT01676259

MEK

Cobimetinib

Belvarafenib

(RAF inhibitor)

I

Advanced or metastatic solid tumors

Recruiting

NCT03284502

MEK

Trametinib

LXH254 (RAF inhibitor)

I

NSCLC or melanoma

Recruiting

NCT02974725

MEK

Pimasertib

None

I

N-RAS–mutated locally advanced or metastasis malignant cutaneous melanoma

Recruiting

NCT01693068, NCT00982865

MEK

Pimasertib

SAR405838 (MDM2 antagonist)

I

Advanced solid tumors

Completed

NCT01985191

MEK

Mirdametinib

Lifirfenib

I

Advanced or refractory solid tumors

Recruiting

NCT03905148

p110α

Alpelisib

Capecitabine (nucleoside metabolic inhibitor); paclitaxel (microtubule inhibitor)

I

Patients with PIK3CA mutant metastatic colorectal cancer; PIK3CA-altered metastatic/recurrent gastric cancer

Not yet recruiting

NCT04753203; NCT04526470

p110α

GDC-0077

Entrectinib (pan-TRK inhibitor)

I

Breast cancer and advanced solid tumors

Recruiting

NCT04632992

RAF

PLX8394; TAK-580

None

I, II

Advanced unresectable solid tumors; low-grade glioma

Recruiting

NCT02428712; NCT03429803

RAF

Belvarafenib

None

I

Solid tumors

Completed

NCT02405065

RAF

Belvarafenib

Cobimetinib (MEK inhibitor); cetuximab (anti-EGFR ab); atezolizumab (anti–PD-L1 ab)

I

Advanced or metastatic solid tumors; NRAS-mutant advanced melanoma

Recruiting

NCT03284502; NCT04835805

RAF, EGFR

Lifirfenib

None

I

Solid tumors

Completed

NCT02610361; NCT03641586

RAF, EGFR

Lifirfenib

Mirdametinib (MEK inhibitor)

I

NSCLC with confirmed KRAS mutations

Recruiting

NCT04294160

SHP2

BBP-398; JAB-3068; RMC-4630; RLY-1971; JAB-3312; SH3809

None

I, II

Advanced or metastatic solid tumors

Recruiting

NCT04528836; NCT03565003; NCT03518554; NCT03634982; NCT04252339; NCT04121286; NCT04045496; NCT04843033

SHP2

RMC-4630

LY3214996 (ERK inhibitor); cobimetinib (MEK inhibitor); osimertinib (EGFR inhibitor)

I, II

Advanced or metastatic solid tumors

Not yet recruiting; recruiting

NCT04916236; NCT03989115

SHP2

ERAS-601

Cobimetinib (MEK inhibitor)

I

Advanced or metastatic solid tumors

Recruiting

NCT04670679

SHP2

TNO155

Nazartinib (EGFR inhibitor); spartalizumab (anti–IL-1β antibody); ribociclib (CDK4/6 inhibitor); adagrasib (KRAS-G12C inhibitor); JDQ443 (KRAS-G12C inhibitor)

I, II

Advanced solid tumors

Recruiting

NCT03114319; NCT04000529; NCT04330664; NCT04699188

SOS1

BI 1701963

Trametinib (MEK inhibitor); BI 3011441 (MEK inhibitor); irinotecan (topoisomerase I inhibitor)

I

Advanced or metastatic solid tumors

Recruiting

NCT04111458; NCT04835714; NCT04627142