Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)

Sponsor

Amgen (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04185883

Collaborator

(none)

1,054

Enrollment

Locations

Arms

82.8

Anticipated Duration (Months)

14.2

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To evaluate the safety and tolerability of sotorasib administered in investigational regimens in adult participants with KRAS p.G12C mutant advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors Kirsten Rat Sarcoma (KRAS) pG12C Mutation	Drug: Sotorasib Drug: AMG 404 Drug: trametinib Drug: RMC-4630 Drug: afatinib Drug: pembrolizumab Drug: panitumumab Drug: carboplatin, pemetrexed, docetaxel Drug: atezolizumab Drug: everolimus Drug: palbociclib Drug: MVASI® (bevacizumab-awwb) Drug: TNO155 Drug: FOLFIRI Drug: FOLFOX Drug: Loperamide	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1054 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1b/2, Protocol Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Sotorasib Monotherapy and in Combination With Other Anti-cancer Therapies in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)

Actual Study Start Date :

Dec 17, 2019

Anticipated Primary Completion Date :

Aug 26, 2024

Anticipated Study Completion Date :

Nov 11, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sotorasib + trametinib Experimental: Sotorasib + trametinib Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: trametinib trametinib administered orally as a tablet.
Experimental: Sotorasib + AMG 404 Experimental: Sotorasib + AMG 404 Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: AMG 404 AMG 404 administered as an intravenous (IV) infusion.
Experimental: Sotorasib + RMC-4630 Experimental: Sotorasib + RMC-4630 Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants, with KRAS p.G12C mutant advanced solid tumors.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: RMC-4630 RMC-4630 administered orally as a capsule.
Experimental: Sotorasib + afatinib Experimental:Sotorasib + afatinib Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced non-small cell lung cancer. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: afatinib afatinib administered orally as a tablet.
Experimental: Sotorasib + pembrolizumab Experimental: Sotorasib + pembrolizumab Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: pembrolizumab pembrolizumab administered as an intravenous (IV) infusion.
Experimental: Sotorasib + panitumumab +/- FOLFIRI Experimental: Sotorasib + panitumumab +/- FOLFIRI Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: panitumumab panitumumab administered as an intravenous (IV) infusion. Drug: FOLFIRI FOLFIRI chemotherapy combination of leucovorin administered as an intravenous (IV) injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and irinotecan administered as IV injection.
Experimental: Sotorasib + atezolizumab Sotorasib + atezolizumab Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: atezolizumab atezolizumab administered as an intravenous (IV) injection.
Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, pembrolizumab Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, pembrolizumab Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: pembrolizumab pembrolizumab administered as an intravenous (IV) infusion. Drug: carboplatin, pemetrexed, docetaxel carboplatin, pemetrexed, docetaxel administered as an intravenous (IV) infusion.
Experimental: Sotorasib Monotherapy Experimental: Sotorasib only Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer with brain metastases. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer with brain metastases.	Drug: Sotorasib Sotorasib administered orally as a tablet.
Experimental: Sotorasib + palbociclib Experimental: Sotorasib + palbociclib Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: palbociclib palbociclib administered orally as a tablet.
Experimental: Sotorasib + everolimus Experimental: Sotorasib + everolimus Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: everolimus everolimus administered orally.
Experimental: Sotorasib + trametinib+ panitumumab Experimental: Sotorasib + trametinib+ panitumumab Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS P.G12C mutant advanced colorectal cancer.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: trametinib trametinib administered orally as a tablet. Drug: panitumumab panitumumab administered as an intravenous (IV) infusion.
Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ FOLFIRI or FOLFOX Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ FOLFIRI or FOLFOX Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced colorectal cancer.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: MVASI® (bevacizumab-awwb) MVASI® (bevacizumab-awwb) administered as an intravenous (IV) infusion. Drug: FOLFIRI FOLFIRI chemotherapy combination of leucovorin administered as an intravenous (IV) injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and irinotecan administered as IV injection. Drug: FOLFOX FOLFOX chemotherapy combination of leucovorin administered as intravenous (IV) injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and oxaliplatin administered as IV injection.
Experimental: Sotorasib + TNO155 Dose Exploration and Dose Expansion Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: TNO155 TNO155 administered orally as a capsule.
Experimental: Sotorasib + afatinib + loperamide Dose Expansion • Upon completing the dose exploration part of the study with sotorasib + afatinib, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer, who will receive sotorasib + afatinib + loperamide.	Drug: Sotorasib Sotorasib administered orally as a tablet. Drug: afatinib afatinib administered orally as a tablet. Drug: Loperamide Loperamide administered orally as a capsule.

Outcome Measures

Primary Outcome Measures

Phase 1b: Number of Participants with Dose Limiting Toxicities (DLTs) [12 Months]
Phase 1b: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [12 Months]
Phase 1b: Number of Participants with Treatment-related Adverse Events [12 Months]
Phase 1b: Number of Participants with Clinically Significant Changes in Vital Signs [12 Months]
Phase 1b: Number of Participants with Clinically Significant Changes in ECG Measurements [12 Months]
Phase 1b: Number of Participants with Clinically Significant Changes in Laboratory Test Values [12 Months]
Phase 2: Objective Response Rate [12 Months]

Secondary Outcome Measures

Phase 1b: Maximum Plasma Concentration (Cmax) [12 Months]
Phase 1b: Time to Maximum Plasma Concentration (Tmax) [12 Months]
Phase 1b: Area Under the Plasma Concentration-time Curve (AUC) [12 Months]
Phase 1b: Objective Response Rate [12 Months]
Phase 1b: Disease Control Rate [12 Months]
Phase 1b: Duration of Response [12 Months]
Phase 1b: Progression-free Survival [12 Months]
Phase 1b: Duration of Stable Disease [12 Months]
Phase 1b: Time to Response [12 Months]
Phase 1b: Overall Survival [12 Months]
Phase 1b: Sotorasib + EGFR Inhibitor +/- Chemotherapeutic Regimen Only: Quantification of Plasma Levels [12 Months]
Phase 1b: Sotorasib Monotherapy Only: Intracranial Objective Response Rate [12 Months]
Intracranial objective response rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM).
Phase 1b: Sotorasib Monotherapy Only: Intracranial Disease Control Rate [12 Months]
Intracranial disease control rate assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM).
Phase 1b: Sotorasib Monotherapy Only: Intracranial Duration of Response [12 Months]
Intracranial duration of response assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM).
Phase 1b: Sotorasib Monotherapy Only: Time to Intracranial Radiation Therapy [12 Months]
Phase 1b: Sotorasib Monotherapy Only: Intracranial Progression-free Survival (PFS) [12 Months]
Intracranial PFS assessed per Response Assessment in Neuro-oncology Brain Metastases (RANO-BM)
Phase 1b: Sotorasib Monotherapy Only: Non-intracranial Progression-free Survival (PFS) [12 Months]
Non-intracranial PFS assessed per RECIST 1.1.
Phase 1b: Sotorasib Monotherapy Only: Overall Progression-free Survival (PFS) [12 Months]
Overall PFS assessed per RECIST 1.1 and RANO-BM.
Phase 1b: Sotorasib + TNO155 Only: Best Overall Response [12 Months]
Phase 2: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [12 Months]
Phase 2: Number of Participants with Grade ≥3 Treatment-emergent Adverse Events (TEAEs) [12 Months]
Phase 2: Maximum Plasma Concentration (Cmax) [12 Months]
Phase 2: Time to Maximum Plasma Concentration (Tmax) [12 Months]
Phase 2: Area Under the Plasma Concentration-time Curve (AUC) [12 Months]
Phase 2: Disease Control Rate [12 Months]
Phase 2: Duration of Response [12 Months]
Phase 2: Progression-free Survival [12 Months]
Phase 2: Time to Response [12 Months]
Phase 2: Overall Survival [12 Months]
Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Dose Limiting Toxicities (DLTs) [12 Months]
Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [12 Months]
Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Treatment-related Adverse Events [12 Months]
Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Vital Signs [12 Months]
Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in ECG Measurements [12 Months]
Phase 1b: Sotorasib + Afatinib + Loperamide Only: Number of Participants with Clinically Significant Changes in Laboratory Test Values [12 Months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men or women greater than or equal to 18 years old.
Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing performed according to in-country requirements. In the United States, this test must be performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.

Exclusion Criteria:

Primary brain tumor.
Spinal cord compression, or untreated, or symptomatic, or active brain metastases, or leptomeningeal disease 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 and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates Professional Corporation	Tucson	Arizona	United States	85711
2	City of Hope National Medical Center	Duarte	California	United States	91010
3	University of California San Diego Moores Cancer Center	La Jolla	California	United States	92093
4	Loma Linda University Cancer Center	Loma Linda	California	United States	92354
5	University of Southern California, Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
6	University of California Davis Medical Center	Sacramento	California	United States	95817
7	University of California at SF	San Francisco	California	United States	94115
8	University of California Los Angeles	Santa Monica	California	United States	90404
9	Rocky Mountain Cancer Centers Denver Midtown	Denver	Colorado	United States	80218
10	Sarah Cannon Research Institute at HealthONE	Denver	Colorado	United States	80218
11	Yale Cancer Center	New Haven	Connecticut	United States	06520
12	Norwalk Hospital	Norwalk	Connecticut	United States	06856
13	Memorial Cancer Institute	Pembroke Pines	Florida	United States	33028
14	Moffitt Cancer Center	Tampa	Florida	United States	33612
15	Emory University	Atlanta	Georgia	United States	30332
16	Northwestern University	Chicago	Illinois	United States	60637
17	University of Chicago Medical Center	Chicago	Illinois	United States	60637
18	Indiana University	Indianapolis	Indiana	United States	46202
19	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
20	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21224
21	University of Michigan	Ann Arbor	Michigan	United States	48109-5912
22	Henry Ford Health System	Detroit	Michigan	United States	48202
23	Washington University	Saint Louis	Missouri	United States	63110-1093
24	Montefiore Medical Center	Bronx	New York	United States	10461
25	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
26	Icahn School of Medicine at Mount Sinai	New York	New York	United States	10029
27	Columbia University Medical Center	New York	New York	United States	10032
28	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
29	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
30	Duke University Medical Center	Durham	North Carolina	United States	27710
31	University of Cincinnati Medical Center	Cincinnati	Ohio	United States	45267
32	Cleveland Clinic	Cleveland	Ohio	United States	44195
33	Providence Portland Medical Center	Portland	Oregon	United States	97213
34	Oregon Health and Science University	Portland	Oregon	United States	97239
35	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
36	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
37	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19111
38	University of Pittsburgh Medical Center Cancer Pavillion	Pittsburgh	Pennsylvania	United States	15232
39	Gibbs Cancer Center and Research Institute - Spartanburg	Spartanburg	South Carolina	United States	29303
40	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57108
41	Henry Joyce Cancer Center	Nashville	Tennessee	United States	37232
42	Texas Oncology - Austin Midtown	Austin	Texas	United States	78705
43	Mary Crowley Cancer Research	Dallas	Texas	United States	75230
44	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
45	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
46	Texas Oncology-Tyler	Tyler	Texas	United States	75702
47	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
48	United States Oncology Regulatory Affairs Corporate Office	Fairfax	Virginia	United States	22031
49	US Oncology Research Investigational Products Center	Fairfax	Virginia	United States	22031
50	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
51	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109-1023
52	Northwest Cancer Specialists - Vancouver	Vancouver	Washington	United States	98684
53	Nepean Cancer Centre	Kingswood	New South Wales	Australia	2747
54	GenesisCare -North Shore (Oncology)	St Leonards	New South Wales	Australia	2065
55	Icon Cancer Care South Brisbane	South Brisbane	Queensland	Australia	4101
56	The Queen Elizabeth Hospital	Woodville South	South Australia	Australia	5011
57	St John of God Healthcare	Subiaco	Western Australia	Australia	6008
58	Medizinische Universitaet Graz	Graz		Austria	8036
59	Universitaetsklinikum Salzburg	Salzburg		Austria	5020
60	Universite Catholique de Louvain Cliniques Universitaires Saint Luc	Bruxelles		Belgium	1200
61	Universitair Ziekenhuis Antwerpen	Edegem		Belgium	2650
62	CHU de Quebec Hopital de l Enfant Jesus	Quebec		Canada	G1J 1Z4
63	Charite Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum	Berlin		Germany	13353
64	Universitaetsklinikum Carl Gustav Carus	Dresden		Germany	01307
65	Aichi Cancer Center	Nagoya-shi	Aichi	Japan	464-8681
66	National Cancer Center Hospital East	Kashiwa-shi	Chiba	Japan	277-8577
67	Seoul National University Hospital	Seoul		Korea, Republic of	03080
68	The Catholic University of Korea Seoul St Marys Hospital	Seoul		Korea, Republic of	06591
69	Asan Medical Center	Seoul		Korea, Republic of	138-736
70	Hospital Universitari Vall d Hebron	Barcelona	Cataluña	Spain	08035
71	Hospital Clinic i Provincial de Barcelona	Barcelona	Cataluña	Spain	08036
72	Instituto Catalan de Oncologia Hospital Duran i Reynals	Hospitalet de Llobregat	Cataluña	Spain	08908
73	Hospital Universitario Ramon y Cajal	Madrid		Spain	28034
74	Hospital Universitario 12 de Octubre	Madrid		Spain	28041