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Table 1 Direct KRASG12C Inhibitors in Clinical Trials

From: The path to the clinic: a comprehensive review on direct KRASG12C inhibitors

Agent

Company

Identifier

Phase

Status

Details

JNJ-74699157 (ARS-3248)

Janssen Research & Development, LLC

NCT04006301

1

Completed

Non-randomized, open-label study examining monotherapy in patients with advanced solid tumors (e.g., NSCLC, CRC) harboring the KRASG12C mutation. Results unavailable.

AMG510 (sotorasib)

Amgen

NCT03600883

1/2

Recruiting

CodeBreaK100. Randomized, open-label study examining AMG510 alone and in combination with anti (PD-1/L1) in patients with advanced solid tumors with KRAS p.G12C mutation, and AMG510 alone in patients with naïve (i.e., previously untreated) advanced NSCLC with KRAS p.G12C mutation.

NCT04185883

1b/2

Recruiting

CodeBreaK101. Non-randomized, open-label study assessing AMG510 alone and in combination with other anti-cancer therapies in patients with advanced solid tumors with KRAS p.G12C mutation. Treatment arms include monotherapy in patients with advanced NSCLC with brain metastases; in combination with trametinib (MEK1/2 inhibitor), AMG 404 (PD-1 inhibitor), RMC-4630 (SHP2 inhibitor), palbociclib (CDK4/6 inhibitor), or everolimus (mTOR inhibitor) in patients with advanced solid tumors; in combination with afatinib (pan-ErbB inhibitor), pembrolizumab (PD-1 inhibitor), AMG 404 (PD-1 inhibitor), atezolizumab (PD-L1 inhibitor), or chemotherapy (carboplatin, pemetraxed, and docetaxel) in patients with advanced NSCLC; in combination with panitumumab (EGFR inhibitor) +/− chemotherapy (FOLFIRI), trametinib and panitumumab, or bevacizumab-awwb and chemotherapy (FOLFIRI or FOLFOX) in patients with advanced CRC.

NCT04380753

1

Recruiting

CodeBreaK105. Open-label study assessing monotherapy in patients of Chinese ancestry with advanced/metastatic solid tumors with KRAS p.G12C mutation.

NCT04303780

3

Active, not recruiting

CodeBreaK200. Randomized, open-label study comparing monotherapy vs. docetaxel in patients with previously treated advanced/metastatic NSCLC with KRAS p.G12C mutation.

NCT04933695

2

Not yet recruiting

CodeBreaK201. Randomized, open-label study investigating monotherapy in patients with Stage IV NSCLC with KRASG12C mutation and PD-L1 TPS < 1%, stratified by STK11 co-mutation.

NCT04625647

2

Not yet recruiting

Lung-MAP Treatment Trial sub-study (S1900E). Open-label study evaluating monotherapy in patients with stage IV or recurrent non-squamous NSCLC with KRASG12C mutation.

NCT04667234

 

Expanded access (Available)

Study provides expanded access to and characterize the safety profile of AMG 510 in patients with previously treated locally advanced/unresectable/metastatic NSCLC with KRAS p.G12C mutation in a real-world setting.

MRTX849 (adagrasib)

Mirati Therapeutics Inc.

NCT03785249

1/2

Recruiting

KRYSTAL-1. Non-randomized, open-label clinical trial evaluating MRTX849 alone in patients with advanced/metastatic solid tumors with KRASG12C mutation, in combination with pembrolizumab or afatinib in patients with NSCLC with KRASG12C mutation, or in combination with cetuximab in patients with CRC with KRASG12C mutation.

NCT04330664

1/2

Recruiting

KRYSTAL 2. Non-randomized, open-label study investigating MRTX849 in combination with TNO155 (SHP2 inhibitor) in patients with advanced solid tumors (NSCLC or CRC) with KRASG12C mutation.

NCT04613596

2

Recruiting

KRYSTAL-7. Open-label study examining MRTX849 in combination with pembrolizumab (anti-PD1 antibody) in patients with advanced NSCLC with KRASG12C mutation.

NCT04793958

3

Recruiting

KRYSTAL-10. Randomized, open-label study comparing combination therapy MRTX849 and cetuximab (anti-EGFR antibody) vs. chemotherapy (mFOLFOX6 or FOLFIRI) in patients with advanced/metastatic CRC with KRASG12C mutation.

NCT04685135

3

Recruiting

KRYSTAL-12. Randomized, open-label study comparing monotherapy with docetaxel (taxane) in patients with advanced/metastatic NSCLC with KRASG12C mutation.

NCT04975256

1/1b

Recruiting

KRYSTAL 14. Non-randomized, open-label study assessing MRTX849 in combination with BI 1701963 (SOS1 pan-KRAS inhibitor) in patients with advanced/metastatic solid malignancies (NSCLC or CRC) with KRASG12C mutation.

LY3499446

Eli Lilly and Company

NCT04165031

1/2

Terminated

Randomized, open label study comparing LY3499446 alone and in combination with abemaciclib, cetuximab, or erlotinib vs. docetaxel in patients with advanced/metastatic solid tumors with KRASG12C mutation. Study was terminated due to unexpected toxicity finding.

LY3537982

Eli Lilly and Company

NCT04956640

1

Not yet recruiting

Non-randomized, open-label study investigating LY3537982 alone and in combination with abemaciclib, erlotinib, sintilimab, temuterkib, LY3295668 (aurora A kinase inhibitor), or cetuximab in patients with KRASG12C mutant solid tumors.

GDC-6036

Genentech, Inc.

NCT04449874

1

Recruiting

Non-randomized, open-label study investigating GDC-6036 alone and in combination with atezolizumab, cetuximab, bevacizumab, erlotinib, or GDC-1971 (SHP2 inhibitor) in patients with advanced/metastatic solid tumors with KRASG12C mutation.

D-1553

InventisBio Inc.

NCT04585035

1/2

Recruiting

Non-randomized, open-label study evaluating D-1553 alone and in combination with other drugs used in standard treatment of solid tumors (not specified) in patients with advanced/metastatic solid tumors, including NSCLC and CRC, with KRASG12C mutation.

JDQ443

Novartis Pharmaceuticals

NCT04699188

1b/2

Recruiting

Non-randomized, open-label study assessing monotherapy and in combination with TNO155 (SHP2 inhibitor) and/or spartalizumab (anti-PD1 antibody) in patients with advanced (metastatic or unresectable) KRASG12C mutant solid tumors.

BI 1823911

Boehringer Ingelheim

NCT04973163

1a/1b

Not yet recruiting

Non-randomized, open-label study investigating BI 1823911 alone and in combination with BI 1701963 (SOS1::KRAS pan-KRAS inhibitor) in patients with advanced/metastatic solid tumors (e.g., NSCLC, CRC, pancreatic cancer, or cholangiocarcinoma) with KRASG12C mutation.

  1. Abbreviations: NSCLC non-small cell lung cancer, CRC colorectal cancer