A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)

Study at a glance

From the registry record, last updated by the sponsor on 30 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Sotorasib (AMG 510) Monotherapy in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation and Sotorasib (AMG 510) Combination Therapy in Subjects With Advanced NSCLC With KRAS p.G12C Mutation (CodeBreaK 100)

ClinicalTrials.gov ID

NCT03600883

Acronym / sponsor ID

20170543

Conditions

KRAS p.G12C Mutant Advanced Solid Tumors

Phase

Phase 1/2

Study type

Interventional

Recruitment status

Completed

Enrolment

713 participants (actual)

Lead sponsor

AmgenIndustry (pharma, biotech, devices)

Study start

27 Aug 2018 (actual)

Primary completion

29 May 2026 (actual)

Study completion

29 May 2026 (actual)

First posted

26 Jul 2018 (actual)

Results

Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Sequential

Masking

None (open label)

Number of arms

6

Who may qualify

Ages

18 to 100 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Primary: Number of subjects with treatment-emergent adverse events

   Time frame: 24 Months

   Treatment-emergent adverse events will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy dose comparison

2. Primary: Number of subjects with treatment-related adverse events

   Time frame: 24 Months

   Treatment-related adverse events will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC

3. Primary: Number of subjects with grade ≥3 treatment-emergent adverse events

   Time frame: 24 Months

   Grade ≥3 treatment-emergent adverse events will be a primary outcome measure in the following group: - Phase 2 monotherapy dose comparison

4. Primary: Number of subjects with serious adverse events

   Time frame: 24 Months

   Serious adverse events will be a primary outcome measure in the following group: - Phase 2 monotherapy dose comparison

5. Primary: Number of subjects with adverse events of interest

   Time frame: 24 Months

   Adverse events of interest will be a primary outcome measure in the following group: - Phase 2 monotherapy dose comparison

6. Primary: Number of subjects with clinically significant changes in vital signs

   Time frame: Baseline to 24 Months

   Vital signs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC

7. Primary: Number of subjects with clinically significant changes in physical examination results

   Time frame: Baseline to 24 Months

   Physical examinations will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1

8. Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs)

   Time frame: Baseline to 24 Months

   ECGs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC

9. Primary: Number of subjects with clinically significant changes in clinical laboratory values

   Time frame: Baseline to 24 Months

   Abnormal clinical laboratory values will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC

10. Primary: Number of subjects with dose-limiting toxicities (DLTs)

    Time frame: 21 Days

    DLTs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC

11. Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria

    Time frame: 24 Months

    ORR will be a primary outcome measure in the following group: * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy * Phase 2 monotherapy dose comparison

12. Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria

    Time frame: 24 Months

    DOR will be a primary outcome measure in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC

13. Primary: Disease control as assessed by RECIST 1.1 criteria

    Time frame: 24 Months

    Disease control will be a primary outcome measure in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC

14. Primary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria

    Time frame: 24 Months

    Duration of SD will be a primary outcome measure in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC

15. Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria

    Time frame: 24 Months

    TTR will be a primary outcome measure in the following group: - Phase 1 monotherapy treatment naïve advanced NSCLC

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2026.
• Background: PubMed 31666701Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, Lanman BA, Werner J, Rapaport AS, San Miguel T, Ortiz R, Osgood T, Sun JR, Zhu X, McCarter JD, Volak LP, Houk BE, Fakih MG, O'Neil BH, Price TJ, Falchook GS, Desai J, Kuo J, Govindan R, Hong DS, Ouyang W, Henary H, Arvedson T, Cee VJ, Lipford JR. The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 2019 Nov;575(7781):217-223. doi: 10.1038/s41586-019-1694-1. Epub 2019 Oct 30.
• Background: PubMed 34096690Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, Kato T, Curioni-Fontecedro A, Sacher A, Spira A, Ramalingam SS, Takahashi T, Besse B, Anderson A, Ang A, Tran Q, Mather O, Henary H, Ngarmchamnanrith G, Friberg G, Velcheti V, Govindan R. Sotorasib for Lung Cancers with KRAS p.G12C Mutation. N Engl J Med. 2021 Jun 24;384(25):2371-2381. doi: 10.1056/NEJMoa2103695. Epub 2021 Jun 4.
• Background: PubMed 34919824Fakih MG, Kopetz S, Kuboki Y, Kim TW, Munster PN, Krauss JC, Falchook GS, Han SW, Heinemann V, Muro K, Strickler JH, Hong DS, Denlinger CS, Girotto G, Lee MA, Henary H, Tran Q, Park JK, Ngarmchamnanrith G, Prenen H, Price TJ. Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial. Lancet Oncol. 2022 Jan;23(1):115-124. doi: 10.1016/S1470-2045(21)00605-7. Epub 2021 Dec 15.
• Background: PubMed 32955176Hong DS, Fakih MG, Strickler JH, Desai J, Durm GA, Shapiro GI, Falchook GS, Price TJ, Sacher A, Denlinger CS, Bang YJ, Dy GK, Krauss JC, Kuboki Y, Kuo JC, Coveler AL, Park K, Kim TW, Barlesi F, Munster PN, Ramalingam SS, Burns TF, Meric-Bernstam F, Henary H, Ngang J, Ngarmchamnanrith G, Kim J, Houk BE, Canon J, Lipford JR, Friberg G, Lito P, Govindan R, Li BT. KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors. N Engl J Med. 2020 Sep 24;383(13):1207-1217. doi: 10.1056/NEJMoa1917239. Epub 2020 Sep 20.
• Background: PubMed 34759319Zhao Y, Murciano-Goroff YR, Xue JY, Ang A, Lucas J, Mai TT, Da Cruz Paula AF, Saiki AY, Mohn D, Achanta P, Sisk AE, Arora KS, Roy RS, Kim D, Li C, Lim LP, Li M, Bahr A, Loomis BR, de Stanchina E, Reis-Filho JS, Weigelt B, Berger M, Riely G, Arbour KC, Lipford JR, Li BT, Lito P. Diverse alterations associated with resistance to KRAS(G12C) inhibition. Nature. 2021 Nov;599(7886):679-683. doi: 10.1038/s41586-021-04065-2. Epub 2021 Nov 10.
• Background: PubMed 37098232Dy GK, Govindan R, Velcheti V, Falchook GS, Italiano A, Wolf J, Sacher AG, Takahashi T, Ramalingam SS, Dooms C, Kim DW, Addeo A, Desai J, Schuler M, Tomasini P, Hong DS, Lito P, Tran Q, Jones S, Anderson A, Hindoyan A, Snyder W, Skoulidis F, Li BT. Long-Term Outcomes and Molecular Correlates of Sotorasib Efficacy in Patients With Pretreated KRAS G12C-Mutated Non-Small-Cell Lung Cancer: 2-Year Analysis of CodeBreaK 100. J Clin Oncol. 2023 Jun 20;41(18):3311-3317. doi: 10.1200/JCO.22.02524. Epub 2023 Apr 25.
• Background: PubMed 38010044Dy GK, Govindan R, Velcheti V, Falchook GS, Italiano A, Wolf J, Sacher AG, Takahashi T, Ramalingam SS, Dooms C, Kim DW, Addeo A, Desai J, Schuler M, Tomasini P, Hong DS, Lito P, Tran Q, Jones S, Anderson A, Hindoyan A, Snyder W, Skoulidis F, Li BT. Long-term benefit of sotorasib in patients with KRAS G12C-mutated non-small-cell lung cancer: plain language summary. Future Oncol. 2024 Jan;20(3):113-120. doi: 10.2217/fon-2023-0560. Epub 2023 Nov 27.
• Background: PubMed 38975874Dilly J, Hoffman MT, Abbassi L, Li Z, Paradiso F, Parent BD, Hennessey CJ, Jordan AC, Morgado M, Dasgupta S, Uribe GA, Yang A, Kapner KS, Hambitzer FP, Qiang L, Feng H, Geisberg J, Wang J, Evans KE, Lyu H, Schalck A, Feng N, Lopez AM, Bristow CA, Kim MP, Rajapakshe KI, Bahrambeigi V, Roth JA, Garg K, Guerrero PA, Stanger BZ, Cristea S, Lowe SW, Baslan T, Van Allen EM, Mancias JD, Chan E, Anderson A, Katlinskaya YV, Shalek AK, Hong DS, Pant S, Hallin J, Anderes K, Olson P, Heffernan TP, Chugh S, Christensen JG, Maitra A, Wolpin BM, Raghavan S, Nowak JA, Winter PS, Dougan SK, Aguirre AJ. Mechanisms of Resistance to Oncogenic KRAS Inhibition in Pancreatic Cancer. Cancer Discov. 2024 Nov 1;14(11):2135-2161. doi: 10.1158/2159-8290.CD-24-0177.
• Background: PubMed 39029295Hochmair MJ, Vermaelen K, Mountzios G, Carcereny E, Dooms C, Lee SH, Morocz E, Kato T, Ciuleanu TE, Dy GK, Parente B, O'Byrne KJ, Chu QS, Castro Junior G, Girard N, Snyder W, Tran Q, Kormany W, Houk B, Mehta B, Curioni-Fontecedro A. Sotorasib (960 mg or 240 mg) once daily in patients with previously treated KRAS G12C-mutated advanced NSCLC. Eur J Cancer. 2024 Sep;208:114204. doi: 10.1016/j.ejca.2024.114204. Epub 2024 Jul 5.
• Background: PubMed 39806205Nagase M, Houk B, Vuu I, Cardona P, Dutta S, Lin CW. Population Pharmacokinetics of Sotorasib in Healthy Subjects and Advanced Solid Tumor Patients Harboring a KRASG12C Mutation from Phase 1 and Phase 2 Studies. AAPS J. 2025 Jan 13;27(1):26. doi: 10.1208/s12248-024-01013-6.
• Derived from this study: PubMed 36546651Strickler JH, Satake H, George TJ, Yaeger R, Hollebecque A, Garrido-Laguna I, Schuler M, Burns TF, Coveler AL, Falchook GS, Vincent M, Sunakawa Y, Dahan L, Bajor D, Rha SY, Lemech C, Juric D, Rehn M, Ngarmchamnanrith G, Jafarinasabian P, Tran Q, Hong DS. Sotorasib in KRAS p.G12C-Mutated Advanced Pancreatic Cancer. N Engl J Med. 2023 Jan 5;388(1):33-43. doi: 10.1056/NEJMoa2208470. Epub 2022 Dec 21.
• Derived from this study: PubMed 31820981Lanman BA, Allen JR, Allen JG, Amegadzie AK, Ashton KS, Booker SK, Chen JJ, Chen N, Frohn MJ, Goodman G, Kopecky DJ, Liu L, Lopez P, Low JD, Ma V, Minatti AE, Nguyen TT, Nishimura N, Pickrell AJ, Reed AB, Shin Y, Siegmund AC, Tamayo NA, Tegley CM, Walton MC, Wang HL, Wurz RP, Xue M, Yang KC, Achanta P, Bartberger MD, Canon J, Hollis LS, McCarter JD, Mohr C, Rex K, Saiki AY, San Miguel T, Volak LP, Wang KH, Whittington DA, Zech SG, Lipford JR, Cee VJ. Discovery of a Covalent Inhibitor of KRASG12C (AMG 510) for the Treatment of Solid Tumors. J Med Chem. 2020 Jan 9;63(1):52-65. doi: 10.1021/acs.jmedchem.9b01180. Epub 2019 Dec 24.
• AmgenTrials clinical trials websiteLink provided by the sponsor.
• Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

133 sites in 16 countries: see every site and its status.