KRAS p.G12C mutant advanced NSCLC, CRC, and other solid tumors MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10061451 Term: Colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Sotorasib
Product Code: AMG 510
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Sotorasib
Current Sponsor code: AMG 510
Other descriptive name: AMG 510
Concentration unit: m
Sponsors
Amgen Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Subject has provided informed consent prior to initiation of any study specific activities/procedures 2.Men or women = 18 years old 3.For all parts except 2e: Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing. For phase 2 Part A only, the mutation will be confirmed by central testing prior to enrollment for NSCLC and CRC tumor types only. a.For NSCLC: Phase 1 subjects must have received platinum-based combination therapy and/or targeted therapies (ie, if molecular testing has identified mutations in EGFR, ALK, or proto-oncogene tyrosine-protein kinase ROS [ROS1] or expression of programmed death-ligand [PD-L1]), prior to receiving AMG 510. Phase 2 Part A subjects must have progressed after receiving anti-PD1 or anti-PD-L1 immunotherapy (unless contraindicated) AND/OR platinum-based combination chemotherapy AND targeted therapy if actionable oncogenic driver mutations were identified [ie, EGFR, ALK, and ROS1]). Subjects in phase 2 Part A must have received no more than 3 prior lines of therapy. For all NSCLC subjects, the following guidance should be used: • Adjuvant therapy will count as a line of therapy if the subject progressed on or within 6 months of adjuvant therapy administration. • In locally advanced and unresectable NSCLC, disease progression on or within six months of end of prior curatively intended multimodal therapy will count as a line of therapy. If chemoradiation is followed by planned systemic therapy without documented progression between chemoradiation & systemic therapy, the entire treatment course counts as 1 line of therapy. • Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate line of therapy. b.For CRC: Phase 1 subjects must have received at least 2 prior systemic regimens in the metastatic setting . For those CRC subjects with tumors that are MSI-H, at least 1 of the prior systemic regimens must be treatment with either nivolumab or pembrolizumab if they were clinically able to receive inhibitors and 1 of these agents is approved for that indication in the region or country. Phase 2 subjects must have progressed after receiving luoropyrimidine AND oxaliplatin AND irinotecan. For those CRC subjects with tumors that are MSI-H, at least 1 of the prior systemic regimens must have included an anti-PD1 therapy if they were clinically able to receive inhibitors and 1 of these agents is approved for that indication in the region or country. c.For advanced solid tumor other than NSCLC or CRC or pancreatic cancer: subjects must have received at least one prior systemic therapy or be intolerant or ineligible for available therapies known to provide clinical benefit. Subjects with advanced solid tumor types other than NSCLC or CRC may be enrolled and treated in phase 1 or phase 2 without central confirmation of the KRAS p.G12C mutation. d.For pancreatic cancer:Subjects with locally advanced or metastatic disease may be enrolled with or without prior treatment. Subjects may be enrolled and treated in phase 2 without central confirmation of the KRAS p.G12C mutation. 4.Subjects willing to provide archived tumor tissue samples (formalin fixed, paraffin embedded [FFPE] sample collected within 5 years) or willing to undergo pre- treatment tumor biopsy. Phase 1 subjects with all tumor types and phase 2 subjects with tumor types other than NSCLC or CRC with prior molecularly confirmed KRAS p.G12C muta
Exclusion criteria
Exclusion criteria: 1. Active brain metastases from non-brain tumors. 2. History or presence of hematological malignancies unless curatively treated with no evidence of disease = 2 years 3. Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure, unstable angina, or cardiac arrhythmia requiring medication 4. 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) 5. Active infection requiring IV antibiotics within 1 weeks of study enrolment (day 1) 6. Exclusion of hepatitis infection, 7. Known positive test for HIV 8. Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to CTCAE version 5.0 grade 0 or 1, or to levels dictated in the eligibility criteria. 9. 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 10. Therapeutic or palliative radiation therapy within 2 weeks of study day 1. Subjects must have recovered from all radiotherapy related toxicity. 11. 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) 12. Other investigational procedures are excluded 13. Previous treatment with a KRASG12C inhibitor 14. Major surgery within 28 days of study day 1 15. Monotherapy with AMG 510: Men and women of childbearing potential (WOCBP) who are unwilling to practice acceptable methods of birth control during treatment and for at least 7 days (women) or 7 days (men) after receiving the last dose of AMG 510. Acceptable methods of highly effective birth control for women include sexual abstinence (refraining from heterosexual intercourse); vasectomy (women with a single male sexual partner) with testing showing there is no sperm in the semen; bilateral tubal ligation or occlusion; or intrauterine device. Acceptable methods of birth control for men include sexual abstinence (refraining from heterosexual intercourse); vasectomy with testing showing there is no sperm in the semen; bilateral tubal ligation or occlusion in the partner; or a condom (the female partner should also consider a form of birth control). Combination Therapy (pembrolizumab plus AMG 510): WOBCP who are unwilling to practice the above-mentioned highly effective methods of birth control during treatment with pembrolizumab plus AMG 510 and for at least 4 months after receiving the last dose of any study drug. 16. Women who are lactating/breast feeding or who plan to breastfeed while on study through 7 days (or 4 months if receiving combination therapy with pembrolizumab) after receiving the last dose of study drug. 17. Women with a positive pregnancy test. 18. Women planning to become pregnant while on study through 7 days (or 4 months if receiving combination therapy with pembrolizumab) after receiving the last dose of study drug 19. Subject has known sensitivity to any of the products to be administered during dosing 20. Subject will not be available for protocol-required study visits or procedures, to the best of the subject and investigator’s knowledge 21. Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Phase 1 Part 1a/2a Incidence of treatment-emergent adverse events, treatment-related adverse events, and clinically significant changes in vital signs, physical examinations, electrocardiograms (ECGs), and clinical laboratory tests Subject incidence of dose-limiting toxicity (DLT) Part 1b/2b and 1d/2d Incidence of DLTs, treatment-emergent adverse events, treatment related adverse events, and changes in vital signs, ECGs, and clinical laboratory tests Part 1c/2c Incidence of DLTs, treatment-emergent adverse events, treatment related adverse events, and clinically significant changes in vital signs, physical examinations, ECGs, and clinical laboratory tests Part 2e Incidence of DLTs, treatment-emergent adverse events, treatment related adverse events, and changes in vital signs, ECGs, and clinical laboratory tests Objective response (OR = complete response [CR] + partial response [PR]), duration of response (DOR), disease control (CR + PR + stable disease [SD]), progression-free survival (PFS), duration of stable disease, and time to response (TTR) measured by computed tomography (CT) or magnetic resonance imaging (MRI) and assessed per RECIST 1.1. Response will be assessed by blinded independent central review (BICR). Complete response and partial response (PR) require confirmatory CT or MRI repeat assessment at least 4 weeks after the first detection of response. Phase 2 Part A Objective response (ORR = CR + PR), measured by CT or MRI and assessed per RECIST 1.1. Response will be assessed by BICR. Complete response and PR require confirmatory CT or MRI repeat assessment at least 4 weeks after the first detection of response. PartB Objective response (ORR = CR + PR), measured by CT or MRI and assessed per RECIST 1.1 Response will be assessed by blinded independent central review (BICR). Complete response and PR require confirmatory CT or MRI repeat assessment at least 4 weeks after the first detection of response. Treatment emergent adverse ev | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 1 Part 1a/2a, 1b/2b, 1d/2d PK parameters of AMG 510 including, but not limited to, maximum plasma concentration (Cmax), time to achieve Cmax (tmax), and area under the plasma concentration-time curve (AUC) OR, DOR, disease control, PFS, duration of stable disease, and TTR measured by CT or MRI and assessed per RECIST 1.1. Response will be assessed by BICR. Complete response and PR require confirmatory CT or MRI repeat assessment at least 4 weeks after the first detection of response. Overall Survival (OS) PK parameters of AMG 510 including, but not limited to, Cmax, tmax, and AUC in the fed and/or fasted state AMG 510 exposure/QTc interval relationship Part 1c/2c PK parameters of AMG 510 including, but not limited to, Cmax, tmax, and AUC OR, DOR, disease control, PFS, duration of stable disease, and TTR measured by CT or MRI and assessed per RECIST 1.1. Response will be assessed by BICR. Complete response and PR require confirmatory CT or MRI repeat assessment at least 4 weeks after the first detection of response. OS Part 2e PK parameters of AMG 510 including, but not limited to Cmax, tmax, and AUC PK parameters for midazolam including, but not limited to: Cmax, AUC, clearance, and t1/2 Phase 2 Part A - Duration of response (DOR) - Disease control rate (DCR) - Time to response (TTR) - Progression-free survival (PFS) - Overall survival (OS) - 6-month PFS and 12 month PFS - 12-month OS Incidence and severity of adverse events PK parameters of AMG 510 including, but not limited to, Cmax, tmax, and AUC. Part B - Duration of response (DOR) - Disease control (DCR = CR + PR + SD) - Depth of response (best percent change from baseline in lesion sum diameters) - Time to response (TTR) - Progression free survival (PFS) - Overall survival (OS) PK parameters of AMG 510 including, but not limited to, Cmax and AUC Changes in cancer-specific symptoms and overall health status using subject reported outcome instruments: - Impact of tre | — |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Greece, Hungary, Japan, Korea, Republic of, Portugal, Romania, Spain, Switzerland, United States
Contacts
Public ContactMedical Information
Amgen GmbH
Outcome results
None listed