Amgen Oncology’s CodeBreaK clinical trial program is evaluating sotorasib in patients with KRAS G12C-mutated cancers.

Please consider referring potentially eligible patients for further evaluation and possible participation in a CodeBreaK clinical trial.


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Sotorasib, a KRASG12C inhibitor

Sotorasib is a small molecule currently under investigation that is designed to specifically and irreversibly inhibit the KRASG12C protein.

CodeBreaK Clinical Trials

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A clinical trial for patients with advanced solid tumors that harbor a KRAS G12C mutation

Status
Recruiting

PHASE

Phase 1/2

CONDITION

Advanced solid tumors, including NSCLC

STUDY DRUG

Sotorasib alone or combined with another anti-cancer therapy

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A clinical trial for patients with advanced solid tumors that harbor a KRAS G12C mutation

Status
Recruiting

PHASE

Phase 1b/2

CONDITION

Advanced solid tumors, including NSCLC

STUDY DRUG

Sotorasib and other anti-cancer therapies

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A clinical trial for patients with non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS G12C mutation

Status
ACTIVE, NOT RECRUITING

PHASE

Phase 3

CONDITION

Non-small cell lung cancer

STUDY DRUG

Sotorasib or docetaxel

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A clinical trial for patients with untreated stage IV non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS G12C mutation

Status
Recruiting

PHASE

Phase 2

CONDITION

Metastatic NSCLC

STUDY DRUG

Sotorasib

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A clinical trial for patients with previously treated metastatic colorectal cancer (mCRC) whose tumors harbor a KRAS G12C mutation

Status
Recruiting

PHASE

Phase 3

CONDITION

Metastatic CRC

STUDY DRUG

Sotorasib plus panitumumab OR
Trifluridine and tipiracil OR
Regorafenib

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A Phase 1/2 Study to Evaluate Sotorasib Monotherapy and Combination Therapy in Subjects With Advanced Solid Tumors that Harbor a KRAS G12C Mutation

ClinicalTrials.gov Identifier:

NCT03600883

Amgen study protocol number:
20170543

Hcp factsheet

Study factsheet

Download a copy of the factsheet.

Download

A Phase 1/2 Study to Evaluate Sotorasib Monotherapy and Combination Therapy in Subjects With Advanced Solid Tumors that Harbor a KRAS G12C Mutation

Study Summary

Indication

KRAS G12C mutant advanced NSCLC, CRC, and other solid tumors

Study treatment

Phase 1: sotorasib monotherapy or combination therapy (sotorasib + PD-1/L1 inhibitor)

Phase 2: sotorasib monotherapy

Key study criteria*

Inclusion

  • Subjects ≥ 18 years old
  • Pathologically documented, locally-advanced or metastatic malignancy with KRAS G12C mutation identified through molecular testing

Exclusion

  • Active brain metastases from non-brain tumors
  • Myocardial infarction within 6 months of study day 1
  • Gastrointestinal tract disease causing the inability to take oral medication

*additional criteria apply

Primary And Secondary Endpoints*

TEAEs, TRAEs, Number of grade ≥ 3 TEAEs, serious AEs, AEs of interest, clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests, DLT, ORR, DOR, DCR, PFS, duration of SD, TTR, OS

*Endpoints vary by study phase/part

Study duration

  • Screening (28 days)
  • Treatment until subject has disease progression or discontinues from treatment
  • Safety follow-up (30 days after end of treatment)
  • Long-term follow-up (up to 3 years)

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A Phase 1b/2 Study Evaluating Sotorasib in Combination With Anti-Cancer Therapies in Subjects With Advanced Solid Tumors that Harbor a KRAS G12C Mutation

ClinicalTrials.gov Identifier:

NCT04185883

Amgen study protocol number:
20190135

Hcp factsheet

Study factsheet

Download a copy of the factsheet.
which includes the study schema.

Download

A Phase 1b/2 Study Evaluating Sotorasib in Combination With Anti-Cancer Therapies in Subjects With Advanced Solid Tumors that Harbor a KRAS G12C Mutation

Study Summary

Indication

Locally-advanced or metastatic malignancy that harbors a KRAS G12C mutation

Study treatment

Sotorasib orally once daily monotherapy or in combination with anticancer treatments. Anticancer treatments include:

  • Sotorasib + pembrolizumab (PD-1 inhibitor)
  • Sotorasib + trametinib or sotorasib + trametinib + panitumumab (MEK inhibitor or MEK inhibitor + EGFR antibody)
  • Sotorasib + RMC-4630 (SHP2 allosteric inhibitor)
  • Sotorasib + afatinib (pan-ErbB tyrosine kinase inhibitor)
  • Sotorasib + atezolizumab (PD-L1 inhibitor)
  • Sotorasib + panitumumab or sotorasib + panitumumab + FOLFIRI (EGFR antibody or EGFR antibody + chemotherapy)
  • Sotorasib + carboplatin + pemetrexed or sotorasib + docetaxel (chemotherapy)
  • Sotorasib + AMG 404 (PD-1 inhibitor)
  • Sotorasib + everolimus (mTOR inhibitor)
  • Sotorasib + palbociclib (CDK 4/6 inhibitor)
  • Sotorasib + bevacizumab-awwb + FOLFIRI or sotorasib + bevacizumab-awwb + FOLFOX (VEGF inhibitor + chemotherapy)
  • Sotorasib + TNO155 (SHP2 inhibitor)

Key study criteria*

Inclusion

  • Subjects age ≥ 18 years old
  • Pathologically documented, locally-advanced or metastatic malignancy with KRAS G12C mutation identified through molecular testing

Exclusion

  • Primary brain tumor
  • Spinal cord compression or untreated or active brain metastases or leptomeningeal disease from non-brain tumors
  • Myocardial infarction within 6 months of study day 1
  • Gastrointestinal tract disease causing the inability to take oral medication

*additional criteria apply

Primary endpoints

DLTs, TEAEs, TRAEs, and clinically significant changes in vital signs, ECGs, and clinical laboratory tests, and ORR

Key secondary endpoints

PK parameters of sotorasib and anti-cancer treatments, ORR, DOR, PFS, DCR, time to response and overall survival

Study duration

  • Screening (up to 28 days)
  • Treatment (may continue until evidence of disease progression in certain cases, intolerance to study medication, withdrawal of consent, or end of study)
  • Safety follow-up (30 days after end of treatment)
  • Long-term follow-up (up to 3 years)

CDK, Cyclin-dependent kinase; CRC, colorectal cancer; DCR, disease control rate; DLT, dose-limiting toxicity; DOR, duration of response; ECG, electrocardiogram; EGFR, epidermal growth factor receptor; ErbB, erythroblastic leukemia viral oncogene homolog; KRAS, Kirsten rat sarcoma; MEK, mitogen-activated protein kinase; mTOR, mammalian target of rapamycin; NSCLC, non-small cell lung cancer; ORR, objective response rate; PD-1, programmed cell death protein 1; PFS, progression-free survival; PK, pharmacokinetic; SD, stable disease; SHP2, src homology region 2-containing protein tyrosine phosphatase 2; TEAE, treatment-emergent adverse event; TKI, tyrosine kinase inhibitor; TRAE, treatment-related adverse event

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A Phase 2, Multicenter, Open-label Study of Sotorasib in Subjects With Stage IV NSCLC Whose Tumors Harbor a KRAS G12C Mutation in Need of First-Line Treatment

ClinicalTrials.gov Identifier:

NCT04933695

Amgen study protocol number:
20190288

Hcp factsheet

Study factsheet

Download a copy of the factsheet.
which includes the study schema.

Download

A Phase 2, Multicenter, Open-label Study of Sotorasib in Subjects With Stage IV NSCLC Whose Tumors Harbor a KRAS G12C Mutation in Need of First-Line Treatment

Study Summary

Indication

Untreated stage IV NSCLC that harbors a KRAS G12C mutation

Study treatment

Sotorasib monotherapy (960mg or 240mg daily)

Key study criteria*

Inclusion

  • Age ≥ 18 years
  • Untreated stage IV NSCLC
  • KRAS G12C mutation identified through molecular testing
  • PD-L1 TPS score < 1% and/or STK11 loss of function mutation

Exclusion

  • Mixed small-cell lung cancer and NSCLC histology
  • Prior treatment for metastatic NSCLC unless adjuvant/neoadjuvant therapy was completed 12 months before metastatic disease
  • Active brain metastases from non-brain tumors
  • Myocardial Infarction within 6 months of study Day 1
  • Unable to take or absorb (for example, gastrointestinal tract disease) oral medication
  • Co-administration of proton-pump inhibitors (PPIs) and histamine 2 (H2) receptor antagonists (H2RA)

*additional criteria apply

Primary And Secondary Endpoints

Primary: ORR
Secondary: DCR; DOR; TTR; PFS; OS; TEAEs; TRAEs; Changes in vital signs, ECGs, and clinical laboratory tests

Study duration

  • Screening (28 days)
  • Study treatment until disease progression, unacceptable toxicity, withdrawal of informed consent, or death
    Note: In select cases, subjects may continue on treatment following radiologic progression if they are continuing to demonstrate clinical benefit.
  • Safety follow-up (30 days after end of treatment)
  • Long-term follow-up (up to 5 years after last subject enrolled)

DCR, disease control rate; DOR, duration of response; ECG, electrocardiogram; ORR, objective response rate; OS, overall survival; PD-L1, programmed death-ligand 1; PFS, progression-free survival; STK11, serine/threonine kinase 11; TEAE, treatment-emergent adverse event; TPS, tumor proportion score, TRAE, treatment-related adverse event; TTR, time to response

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A Phase 3, Multicenter, Randomized, Open-label Study of Sotorasib and Panitumumab Versus Investigator’s Choice in Subjects With Previously Metastatic CRC Whose Tumors Harbor a KRAS G12C Mutation

ClinicalTrials.gov Identifier:

NCT05198934

Amgen study protocol number:
20190172

Hcp factsheet

Study factsheet

Download a copy of the factsheet.
which includes the study schema.

Download

A Phase 3, Multicenter, Randomized, Open-label Study of Sotorasib and Panitumumab Versus Investigator’s Choice in Subjects With Previously Metastatic CRC Whose Tumors Harbor a KRAS G12C Mutation

Study Summary

Indication

Previously treated metastatic CRC that harbors a KRAS G12C mutation

Study treatment

Sotorasib plus panitumumab OR Trifluridine and tipiracil OR Regorafenib

Key study criteria*

Inclusion

  • Age ≥ 18 years
  • Pathologically documented metastatic colorectal adenocarcinoma harboring a KRAS G12C mutation identified through molecular testing
  • Received at least 1 prior line of therapy for metastatic disease. Participants must have received and progressed or experienced disease recurrence on or after fluoropyrimidine, irinotecan, and oxaliplatin
  • ECOG PS ≤ 2
  • Measurable disease per RECIST 1.1 criteria

Exclusion

  • Active brain metastases
  • History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥ 2 years
  • Significant GI disorder that results in significant malabsorption, requirement for IV alimentation, or inability to take oral medication
  • History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis
  • Leptomeningeal disease
  • Previous treatment with a KRASG12C inhibitor

*additional criteria apply

Primary And Secondary Endpoints

Primary: PFS
Secondary: OS, ORR, DOR, TTR, DCR, investigator-assessed ORR, investigator-assessed PFS

Study duration

  • Screening (up to 28 days)
  • Study treatment until disease progression, unacceptable toxicity, withdrawal of informed consent, or death
    Note: In select cases, subjects may continue on treatment following radiologic progression if they are continuing to demonstrate clinical benefit
  • Safety follow-up (28 ± 7 days after end of treatment)
  • Long-term follow-up (up to 1 year after last subject enrolled)

CRC, colorectal cancer; DCR, disease control rate; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; GI, gastrointestinal; IV, intravenous; KRAS, Kirsten rat sarcoma; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RECIST, Response Evaluation Criteria In Solid Tumors; TTR, time to response

KRAS G12C is an oncogenic driver mutation in multiple cancer types

KRAS mutations can play a role in some of the most common cancers, including lung, colorectal, and pancreatic cancers. The KRAS G12C mutation is an oncogenic driver occurring in approximately 13% of non-squamous non-small cell lung cancer (NSCLC), and 1-3% of other solid tumors, such as colorectal cancer.1,2,3

Watch this video to learn more about how KRAS G12C mutations contribute to oncogenesis.



Targeting a unique surface groove on KRASG12C

Amgen is investigating ways to target mutant KRAS. Recent scientific advancements have revealed a binding site in the inactive state of KRASG12C. The mutant cysteine resides next to a narrow surface pocket, the P2 pocket, providing a potential binding target for covalent inhibitors, such as sotorasib.4,5,6

References: 1. Cox AD, Fesik SW, Kimmelman AC, Luo J, Der CJ. Nat Rev Drug Discov. 2014;13(11):828-851. 2. Biernacka A, Tsongalis PD, Peterson JD, et al. Cancer Genet. 2016;209(5):195-198. 3. Neumann J, Zeindl-Eberhart E, Kirchner T, Jung A. Pathol Res Pract. 2009;205:858-862. 4. Ryan MB, Corcoran RB. Nat Rev Clin Oncol. 2018;15(11):709-720. 5. Lanman BA, Chen JJ, Liu L, et al. Cancer Res. 2019;79(suppl 13):abstract 4455. 6. Canon J, Rex K, Saiki AY, et al. Nature. 2019;575(7781):217-223.