History of Changes for Study: NCT03600883

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

A study version is represented by a row in the table.
Select two study versions to compare. One each from columns A and B.
Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
Click "Compare" to do the comparison and show the differences.
Select a version's Submitted Date link to see a rendering of the study for that version.
The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
Hover over the "Recruitment Status" to see how the study's recruitment status changed.
Study edits or deletions are displayed in red.
Study additions are displayed in green.

Study Record Versions

Version	Submitted Date	Changes
1	July 17, 2018	None (earliest Version on record)
2	August 7, 2018	Study Status, Eligibility, Arms and Interventions and Study Identification
3	September 14, 2018	Recruitment Status, Study Status, Contacts/Locations and Oversight
4	October 29, 2018	Study Status, IPDSharing and Contacts/Locations
5	November 21, 2018	Study Status and Contacts/Locations
6	January 30, 2019	Study Status and Contacts/Locations
7	March 11, 2019	Study Status, Contacts/Locations and Eligibility
8	March 13, 2019	Contacts/Locations and Study Status
9	April 3, 2019	Study Status and Contacts/Locations
10	May 30, 2019	Arms and Interventions, Study Status, Study Identification, Contacts/Locations, Eligibility, Study Design, Conditions and Study Description
11	June 5, 2019	Study Status and Contacts/Locations
12	July 17, 2019	Study Status and Contacts/Locations
13	July 31, 2019	Study Status, Contacts/Locations and Study Design
14	August 21, 2019	Study Status and Contacts/Locations
15	September 19, 2019	Study Status and Contacts/Locations
16	September 25, 2019	Contacts/Locations and Study Status
17	October 9, 2019	Study Status and Contacts/Locations
18	November 27, 2019	Study Status, Arms and Interventions, Outcome Measures, IPDSharing, Contacts/Locations, Study Design and Study Identification
19	December 20, 2019	Study Status, Study Identification, References and Contacts/Locations
20	January 8, 2020	Study Status and Contacts/Locations
21	January 15, 2020	Study Status and Contacts/Locations
22	February 12, 2020	Study Status and Contacts/Locations
23	February 19, 2020	Contacts/Locations and Study Status
24	April 8, 2020	Study Status, Contacts/Locations and Study Design
25	April 15, 2020	Study Status and Contacts/Locations
26	April 29, 2020	Contacts/Locations and Study Status
27	May 6, 2020	Study Status
28	May 13, 2020	Study Status
29	June 10, 2020	Study Status and Contacts/Locations
30	June 12, 2020	Contacts/Locations and Study Status
31	June 25, 2020	Contacts/Locations and Study Status
32	July 23, 2020	Contacts/Locations and Study Status
33	September 16, 2020	Contacts/Locations and Study Status
34	September 21, 2020	Contacts/Locations and Study Status
35	September 23, 2020	Contacts/Locations and Study Status
36	October 1, 2020	Contacts/Locations and Study Status
37	October 30, 2020	Contacts/Locations and Study Status
38	November 13, 2020	Study Status and Contacts/Locations
39	December 11, 2020	Study Status and Contacts/Locations
40	December 14, 2020	Contacts/Locations, Study Status, Eligibility and Arms and Interventions
41	December 29, 2020	Contacts/Locations and Study Status
42	January 15, 2021	Contacts/Locations and Study Status
43	February 11, 2021	Study Status and Contacts/Locations
44	March 12, 2021	Study Status and Contacts/Locations
45	March 25, 2021	Contacts/Locations and Study Status
46	May 7, 2021	Outcome Measures, Contacts/Locations, Arms and Interventions, Study Status, Study Design and Study Identification
47	May 21, 2021	Contacts/Locations and Study Status
48	May 26, 2021	Contacts/Locations and Study Status
49	May 28, 2021	Study Status
50	June 4, 2021	Contacts/Locations and Study Status
51	July 1, 2021	Study Status and References
52	July 7, 2021	Contacts/Locations and Study Status
53	July 14, 2021	Study Status and Contacts/Locations
54	August 3, 2021	Study Status
55	August 11, 2021	Study Status and Contacts/Locations
56	September 1, 2021	Study Status and Contacts/Locations
57	October 15, 2021	Study Status, Contacts/Locations and Outcome Measures
58	October 27, 2021	Study Status and Contacts/Locations
59	November 3, 2021	Study Status and Contacts/Locations
60	November 12, 2021	Study Status and Contacts/Locations
61	November 24, 2021	Contacts/Locations and Study Status
62	December 22, 2021	Contacts/Locations and Study Status
63	December 29, 2021	Contacts/Locations and Study Status
64	January 19, 2022	Study Status and Contacts/Locations
65	January 26, 2022	Contacts/Locations and Study Status
66	February 18, 2022	Arms and Interventions, Study Status, Contacts/Locations, Outcome Measures, Study Identification, Study Design and Study Description
67	June 1, 2022	Study Status and References
68	June 22, 2022	Study Status
69	September 1, 2022	Study Status, References and Contacts/Locations
70	September 21, 2022	Contacts/Locations and Study Status
71	September 30, 2022	Recruitment Status, Study Status, Contacts/Locations and Study Design
72	October 12, 2022	Study Status
73	November 14, 2022	Study Status
74	January 9, 2023	Study Status and References
75	March 24, 2023	Study Status
76	May 19, 2023	Study Status
77	October 23, 2023	Study Status and Arms and Interventions
78	February 22, 2024	Study Status and References
79	May 10, 2024	Study Status and References

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	20170543
Brief Title:	A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreak 100)
Official Title:	A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 510 Monotherapy in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation and AMG 510 Combination Therapy in Subjects With Advanced NSCLC With KRAS p.G12C Mutation (CodeBreak 100)
Secondary IDs:

Study Status


Record Verification:	July 2020
Overall Status:	Recruiting
Study Start:	August 27, 2018
Primary Completion:	January 29, 2022 [Anticipated]
Study Completion:	December 31, 2023 [Anticipated]

First Submitted:	June 26, 2018
First Submitted that Met QC Criteria:	July 17, 2018
First Posted:	July 26, 2018 [Actual]

Last Update Submitted that Met QC Criteria:	July 23, 2020
Last Update Posted:	July 24, 2020 [Actual]

Sponsor/Collaborators


Sponsor:	Amgen
Responsible Party:	Sponsor
Collaborators:

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	No

Study Description

Brief Summary:

Evaluate the safety and tolerability of AMG 510 in adult subjects with KRAS p.G12C mutant advanced solid tumors.

Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult subjects with KRAS p.G12C mutant advanced solid tumors.

Detailed Description:

Conditions


Conditions:	KRAS p.G12C Mutant Advanced Solid Tumors
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 1/Phase 2
Interventional Study Model:	Sequential Assignment
Number of Arms:	5
Masking:	None (Open Label)
Allocation:	Non-Randomized
Enrollment:	533 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Experimental: Dose Exploration Part 1 monotherapy Cohorts with food effect and alternative dosing regimens Enrollment into the dose exploration cohorts may be from any eligible solid tumor type. Dose escalation will begin with 2-4 subjects treated at the lowest planned dose level of 180 mg. If no DLT is observed, dose escalation will continue to the next planned dose cohort	Drug: AMG 510 Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation
Experimental: Dose Expansion Part 2 monotherapy Upon completing the dose exploration part of the study, dose expansion may proceed with 2 groups consisting of subjects with KRAS p.G12C mutant advanced solid tumors Dose expansion in these 2 groups may be done concurrently	Drug: AMG 510 Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation
Experimental: Phase 2 monotherapy Additional subjects will be enrolled in the dose expansion to confirm the recommended phase 2 dose. Enrollment into phase 2 will be opened after confirmation of the recommended phase 2 dose	Drug: AMG 510 Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation
Experimental: Combination arm with AMG 510 and anti PD-1/L1 Additional subjects will be enrolled into the combination arm with AMG 510 in combination with an anti (PD-1/L1)	Drug: AMG 510 Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation
Experimental: Monotherapy treatment naive advanced NSCLC Separate cohort of part 1 dose expansion patients to evaluate the safety and clinical activity of AMG 510 administered orally once daily in patients with previously untreated advanced NSCLC	Drug: AMG 510 Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation

Outcome Measures


Primary Outcome Measures:
1.	Number of Participants With Abnormal Laboratory Values [ Time Frame: 24 Months ]
2.	Number of subjects with clinically significant changes in vital signs. [ Time Frame: 24 Months ]
3.	Number of subjects with changes on ECG. [ Time Frame: 24 Months ]
4.	Objective response rate (ORR) assessed by RECIST 1.1 criteria of AMG 510 as monotherapy in subjects with KRAS p.G12C mutated advanced tumors [ Time Frame: 24 Months ]
Secondary Outcome Measures:
1.	Plasma concentration (Cmax) [ Time Frame: 24 Months ]
2.	Time to achieve Cmax (tmax) [ Time Frame: 24 Months ]
3.	Area under the plasma concentration-time curve (AUC) [ Time Frame: 24 Months ]
4.	Duration of overall response [ Time Frame: 24 Months ]
5.	Progression-free survival [ Time Frame: 24 Months ]
6.	Duration of stable disease [ Time Frame: 24 Months ]

Eligibility


Minimum Age:	18 Years
Maximum Age:	100 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
Criteria:	Inclusion Criteria: Men or women greater than or equal to 18 years old. Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12Cmutation identified through DNA sequencing. Exclusion Criteria Active brain metastases from non-brain tumors. Myocardial infarction within 6 months of study day 1. Gastrointestinal (GI) tract disease causing the inability to take oral medication.

Contacts/Locations


Central Contact Person:	Amgen Call Center Telephone: 866-572-6436 Email: medinfo@amgen.com
Study Officials:	MD Study Director Amgen
Locations:	United States, California
	Research Site [Recruiting] Duarte, California, United States, 91010
	Research Site [Recruiting] San Francisco, California, United States, 94158
	Research Site [Recruiting] Santa Monica, California, United States, 90403
	Research Site [Recruiting] Santa Monica, California, United States, 90404
	United States, Colorado
	Research Site [Recruiting] Denver, Colorado, United States, 80218
	Research Site [Recruiting] Lone Tree, Colorado, United States, 80124
	United States, Connecticut
	Research Site [Recruiting] New Haven, Connecticut, United States, 06510
	United States, Delaware
	Research Site [Recruiting] Newark, Delaware, United States, 19713
	United States, Florida
	Research Site [Recruiting] Gainesville, Florida, United States, 32608
	Research Site [Recruiting] Orlando, Florida, United States, 32804
	Research Site [Recruiting] Tampa, Florida, United States, 33612
	United States, Georgia
	Research Site [Recruiting] Atlanta, Georgia, United States, 30322
	United States, Indiana
	Research Site [Recruiting] Indianapolis, Indiana, United States, 46202
	United States, Maryland
	Research Site [Recruiting] Bethesda, Maryland, United States, 20817
	United States, Massachusetts
	Research Site [Recruiting] Boston, Massachusetts, United States, 02114
	Research Site [Recruiting] Boston, Massachusetts, United States, 02215
	United States, Michigan
	Research Site [Recruiting] Ann Arbor, Michigan, United States, 48109
	Research Site [Recruiting] Detroit, Michigan, United States, 48202
	United States, Missouri
	Research Site [Recruiting] Saint Louis, Missouri, United States, 63110
	United States, New York
	Research Site [Recruiting] Buffalo, New York, United States, 14263
	Research Site [Recruiting] New York, New York, United States, 10016
	Research Site [Recruiting] New York, New York, United States, 10065
	United States, North Carolina
	Research Site [Recruiting] Durham, North Carolina, United States, 27710
	United States, Ohio
	Research Site [Recruiting] Cleveland, Ohio, United States, 44106
	Research Site [Recruiting] Cleveland, Ohio, United States, 44195
	United States, Pennsylvania
	Research Site [Recruiting] Philadelphia, Pennsylvania, United States, 19104
	Research Site [Recruiting] Philadelphia, Pennsylvania, United States, 19111
	Research Site [Recruiting] Pittsburgh, Pennsylvania, United States, 15213
	United States, South Carolina
	Research Site [Recruiting] Spartanburg, South Carolina, United States, 29303
	United States, Tennessee
	Research Site [Recruiting] Nashville, Tennessee, United States, 37203
	Research Site [Recruiting] Nashville, Tennessee, United States, 37232
	United States, Texas
	Research Site [Recruiting] Austin, Texas, United States, 78731
	Research Site [Recruiting] Dallas, Texas, United States, 75246
	Research Site [Recruiting] Dallas, Texas, United States, 75390
	Research Site [Recruiting] Houston, Texas, United States, 77030
	Research Site [Recruiting] Irving, Texas, United States, 75063
	United States, Utah
	Research Site [Recruiting] Salt Lake City, Utah, United States, 84112
	United States, Virginia
	Research Site [Recruiting] Blacksburg, Virginia, United States, 24060
	Research Site [Recruiting] Fairfax, Virginia, United States, 22031
	United States, Washington
	Research Site [Recruiting] Seattle, Washington, United States, 98109
	Australia, New South Wales
	Research Site [Recruiting] Randwick, New South Wales, Australia, 2031
	Australia, Queensland
	Research Site [Recruiting] Woolloongabba, Queensland, Australia, 4102
	Australia, South Australia
	Research Site [Recruiting] Woodville South, South Australia, Australia, 5011
	Australia, Victoria
	Research Site [Recruiting] Melbourne, Victoria, Australia, 3000
	Austria
	Research Site [Recruiting] Graz, Austria, 8036
	Research Site [Recruiting] Innsbruck, Austria, 6020
	Research Site [Recruiting] Krems, Austria, 3500
	Research Site [Recruiting] Wien, Austria, 1090
	Belgium
	Research Site [Recruiting] Bruxelles, Belgium, 1000
	Research Site [Recruiting] Edegem, Belgium, 2650
	Research Site [Recruiting] Gent, Belgium, 9000
	Research Site [Recruiting] Leuven, Belgium, 3000
	Brazil
	Research Site [Recruiting] Rio De Janeiro, Brazil, 22793-080
	Brazil, Rio Grande Do Sul
	Research Site [Recruiting] Porto Alegre, Rio Grande Do Sul, Brazil, 90050-170
	Research Site [Recruiting] Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
	Brazil, Sao Paulo
	Research Site [Recruiting] São Paulo, Sao Paulo, Brazil, 01308-050
	Research Site [Recruiting] São Paulo, Sao Paulo, Brazil, 04501-000
	Brazil, São Paulo
	Research Site [Recruiting] São José do Rio Preto, São Paulo, Brazil, 15090-000
	Canada, Alberta
	Research Site [Recruiting] Calgary, Alberta, Canada, T2N 4N2
	Research Site [Recruiting] Edmonton, Alberta, Canada, T6G 1Z2
	Canada, Ontario
	Research Site [Recruiting] London, Ontario, Canada, N6A 5W9
	Research Site [Recruiting] Ottawa, Ontario, Canada, K1H 8L6
	Research Site [Recruiting] Toronto, Ontario, Canada, M5G 2M9
	France
	Research Site [Recruiting] Bordeaux, France, 33076
	Research Site [Recruiting] Créteil, France, 94010
	Research Site [Recruiting] Marseille cedex 5, France, 13385
	Research Site [Recruiting] Paris Cedex 5, France, 75248
	Research Site [Recruiting] Toulouse cedex 9, France, 31059
	Research Site [Recruiting] Villejuif, France, 94805
	Germany
	Research Site [Recruiting] Essen, Germany, 45147
	Research Site [Recruiting] Köln, Germany, 50937
	Research Site [Recruiting] München, Germany, 81377
	Japan, Aichi
	Research Site [Recruiting] Nagoya-shi, Aichi, Japan, 464-8681
	Japan, Chiba
	Research Site [Recruiting] Kashiwa-shi, Chiba, Japan, 277-8577
	Japan, Ehime
	Research Site [Recruiting] Matsuyama-shi, Ehime, Japan, 791-0280
	Japan, Fukuoka
	Research Site [Recruiting] Fukuoka-shi, Fukuoka, Japan, 811-1395
	Japan, Kanagawa
	Research Site [Recruiting] Kawasaki-shi, Kanagawa, Japan, 216-8511
	Research Site [Recruiting] Yokohama-shi, Kanagawa, Japan, 241-8515
	Japan, Osaka
	Research Site [Recruiting] Hirakata-shi, Osaka, Japan, 573-1191
	Research Site [Recruiting] Osaka-shi, Osaka, Japan, 541-8567
	Japan, Sendai-shi
	Research Site [Recruiting] Miyagi, Sendai-shi, Japan, 980-0873
	Japan, Shizuoka
	Research Site [Recruiting] Sunto-gun, Shizuoka, Japan, 411-8777
	Japan, Tokyo
	Research Site [Recruiting] Koto-ku, Tokyo, Japan, 135-8550
	Japan, Wakayama
	Research Site [Recruiting] Wakayama-shi, Wakayama, Japan, 641-8510
	Korea, Republic of
	Research Site [Recruiting] Seoul, Korea, Republic of, 03080
	Research Site [Recruiting] Seoul, Korea, Republic of, 03722
	Research Site [Recruiting] Seoul, Korea, Republic of, 05505
	Research Site [Recruiting] Seoul, Korea, Republic of, 06591
	Research Site [Recruiting] Seoul, Korea, Republic of, 135-710
	Switzerland
	Research Site [Recruiting] Basel, Switzerland, 4031
	Research Site [Recruiting] Geneve, Switzerland, 1211
	Research Site [Recruiting] Zurich, Switzerland, 8091

IPDSharing


Plan to Share IPD:	Yes De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
	Supporting Information: Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR)
	Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
	Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
	URL: https://www.amgen.com/datasharing

References


Citations:	Canon 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. PubMed 31666701
Links:	URL: http://www.amgentrials.com Description: AmgenTrials clinical trials website
Available IPD/Information: