ClinicalTrials.gov

History of Changes for Study: NCT03600883
A Phase 1, Open-label Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation
Latest version (submitted November 14, 2022) on ClinicalTrials.gov
  • 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 A B 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
Comparison Format:

Scroll up to access the controls

Study NCT03600883
Submitted Date:  July 17, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: 20170543
Brief Title: A Phase 1, Open-label Study Evaluating the Safety, Tolerability, PK, and Efficacy of AMG 510 in Subjects With Solid Tumors With a Specific KRAS Mutation
Official Title: A Phase 1, First-in-Human, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 510 in Subjects With Advanced Solid Tumors With a Specific KRAS Mutation
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2018
Overall Status: Not yet recruiting
Study Start: August 14, 2018
Primary Completion: March 20, 2020 [Anticipated]
Study Completion: September 20, 2021 [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 17, 2018
Last Update Posted: July 26, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Amgen
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
Brief Summary:

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

Estimate the maximum tolerated dose (MTD) and/or a biologically active dose (eg, recommended phase 2 dose [RP2D]) within investigated subject population groups.

Detailed Description:
Open or close this module Conditions
Conditions: Advanced KRAS p.G12C Mutant Solid Tumors
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Sequential Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 60 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Dose Exploration Part 1
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.
Drug: AMG 510
Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation
Experimental: Dose Expansion Part 2
Upon completing the dose exploration part of the study and depending on data obtained, dose expansion may proceed with three groups consisting of subjects with KRAS p.G12C mutant solid tumors Dose expansion in all three groups may be done concurrently.
Drug: AMG 510
Characterize the pharmacokinetics (PK) of AMG 510 following administration as an oral Tablet formulation
Open or close this module 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 ]

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. Objective response rate
[ Time Frame: 24 months ]

5. Duration of overall response
[ Time Frame: 24 Months ]

6. Progression-free survival
[ Time Frame: 24 Months ]

7. Duration of stable disease
[ Time Frame: 24 Months ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 100 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

Subject has provided informed consent prior to initiation of any study specific activities/procedures 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. Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy.

Part 1 (Dose Exploration) - Subjects willing to provide archived tumor samples (fresh frozen sample or formalin fixed, paraffin embedded [FFPE] sample collected within 5 years) or willing to undergo pretreatment tumor biopsy.

Part 2 (Dose Expansion) - Willing to undergo pre-treatment tumor biopsy. Subjects can be allowed to enroll without undergoing tumor biopsy upon agreement with Investigator and the Medical Monitor if tumor biopsy is not feasible.

Measurable or evaluable disease per RECIST 1.1 criteria (Appendix D). Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 2 Life expectancy of greater than 3 months, in the opinion of the investigator Ability to take oral medications and willing to record daily adherence to investigational product QTc less than or equal to 470 msec (based on average of screening triplicates)

Adequate hematological laboratory assessments, as follows:

Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L Platelet count greater than or equal to 75 x 109/L Hemoglobin greater than or equal to 9 g/dL

Adequate renal laboratory assessments, as follows:

Estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation greater than or equal to 60 ml/min/1.73 m2

Adequate hepatic laboratory assessments, as follows:

AST less than 2.5 x ULN (if liver metastases are present, less than or equal to 5 x ULN) ALT less than 2.5 x ULN (if liver metastases are present, less than or equal to 5 x ULN) Alkaline phosphatase less than 2.0 x ULN (if liver or bone metastases are present, less than 3.0 x ULN) Total bilirubin less than 1.5 x ULN (less than 2.0 x ULN for subjects with documented Gilbert's syndrome or less than 3.0 x ULN for subjects for whom the indirect bilirubin level suggests an extrahepatic source of elevation)

Adequate coagulation laboratory assessments, as follows:

Prothrombin time (PT) or partial thromboplastin time (PTT) less than 1.5 x upper limit of normal (ULN), OR International normalized ratio (INR) less than 1.5 or within target range if on prophylactic anticoagulation therapy.

Subject able to eat a standardized high-fat, high-caloric meal within 25 minutes Subject able to fast for greater than or equal to10 hours Subject able to handle collection of his/her urine over a 24 hour period. Pathologically documented, definitively diagnosed KRAS p.G12Cmutant NSCLC Pathologically documented, and definitively diagnosed KRAS p.G12C mutant CRC

Exclusion Criteria:

Active brain metastases from non-brain tumors. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade less than or equal to 2; b) on stable doses of dexamethasone, if applicable; and c) follow-up MRI shows no new lesions appearing History or presence of hematological malignancies unless curatively treated with no evidence of disease Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association greater than class II), unstable angina, or cardiac arrhythmia requiring medication Gastrointestinal (GI) tract disease causing the inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, uncontrolled inflammatory GI disease (eg, Crohn's disease, ulcerative colitis) Active infection requiring intravenous (IV) antibiotics within 1 weeks of study enrollment (day 1) Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic Hepatitis B), positive Hepatitis total core antibody with negative HepBsAg (suggestive of occult hepatitis B) or detectable Hepatitis C virus Ribonucleic acid (RNA) by PCR (indicative of active Hepatitis C - screening is generally done by Hepatitis C Antibody (HepCAb), followed by Hepatitis C virus RNA by PCR if HepCAb is positive) Known positive test for HIV Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (Grade 2 or 3 toxicities from prior anti-tumor therapy that are considered irreversible [defined as having been present and stable for greater than 6 months], such as ifosfamide-related proteinuria, may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor) Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy [except for subjects with breast cancer], or investigational agent) within 28 days of study day 1; concurrent use of hormone deprivation therapy for hormone-refractory prostate cancer or breast cancer is permitted Therapeutic or palliative radiation therapy within 2 weeks of study day 1 Currently enrolled in another investigational device or drug study, or less than 28 days since ending another investigational device or drug study(s), or receiving other investigational agent(s) Other investigational procedures are excluded All herbal medicines (eg, St. John's wort), vitamins, and supplements consumed by the subject within the 30 days prior to receiving the first dose of AMG 510, and continuing use if applicable, will be reviewed by the Principal Investigator and the Amgen Medical Monitor. Written documentation of this review and Amgen acknowledgment is required for subject participation Major surgery within 28 days of study day 1 Men and women of reproductive potential who are unwilling to practice acceptable methods of effective birth control while on study through 1 week (women) or 90 days (men) after receiving the last dose of study drug. Acceptable methods of effective birth control include sexual abstinence (refraining from heterosexual intercourse; men, women); vasectomy; tubal ligation; or a condom with spermicide (men) in combination with barrier methods, hormonal birth control or IUD (women) Women who are lactating/breast feeding or who plan to breastfeed while on study through 1 week after receiving the last dose of study drug.

Women with a positive pregnancy test. Women planning to become pregnant while on study through 1 week after receiving the last dose of study drug Subject has known sensitivity to any of the products to be administered during dosing Subject will not be available for protocol-required study visits or procedures, to the best of the subject and investigator's knowledge Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion Use of known cytochrome P450 (CYP) 3A4 sensitive substrates (with a narrow therapeutic window), within 14 days or 5 half-lives (whichever is longer) of the drug or its major active metabolite, whichever is longer, prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor Use of strong inhibitors of CYP3A4 or P-gp within 14 days or 5 half-lives (whichever is longer) or grapefruit juice or grapefruit containing products within 7 days prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor.

Use of strong inducers of CYP3A4 within 14 days or 5 half-lives (whichever is longer) within 7 days prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor.

Open or close this module Contacts/Locations
Central Contact Person: Amgen Call Center
Telephone: 866-572-6436
Email: medinfo@amgen.com
Study Officials: MD
Study Director
Amgen
Locations:
Open or close this module 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 link below.
URL: http://www.amgen.com/datasharing
Open or close this module References
Links: Description: AmgenTrials clinical trials website
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services