Phase 1/2 Study of MRTX849 in Patients With Cancer Having a KRAS G12C Mutation KRYSTAL-1

Sponsor

Mirati Therapeutics Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT03785249

Collaborator

(none)

740

Enrollment

Locations

Arms

55.5

Anticipated Duration (Months)

9.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors that have a KRAS G12C mutation.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer Metastatic Cancer Malignant Neoplastic Disease	Drug: MRTX849 Drug: Pembrolizumab Drug: Cetuximab Drug: Afatinib	Phase 1/Phase 2

Detailed Description

This study will evaluate the safety, tolerability, pharmacokinetics, metabolites, pharmacodynamics, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumors with a KRAS G12C mutation. MRTX849 (adagrasib) is an orally-available small molecule inhibitor of KRAS G12C.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

740 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Multiple Expansion Cohort Trial of MRTX849 in Patients With Advanced Solid Tumors With KRAS G12C Mutation KRYSTAL-1

Actual Study Start Date :

Jan 15, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Sep 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1 Dose Exploration Dose escalation of MRTX849 to determine maximum tolerated dose	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental: Phase 1b Expansion Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 to recommend Phase 2 regimens	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental: Phase 2 Separate cohorts of patients stratified by histological diagnosis, prior treatment history or co-mutation status (e.g., STK11) for evaluation of clinical activity of MRTX849	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen
Experimental: Pilot Phase 1b Combination with Pembrolizumab Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Pembrolizumab Pembrolizumab is administered as an intravenous infusion once every 3 weeks
Experimental: Pilot Phase 1b Combination with Cetuximab Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Cetuximab Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental: Pilot Phase 1b Combination with Afatinib Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Afatinib Afatinib will be administered orally once a day in a continuous regimen
Experimental: Phase 2 Combination with Cetuximab Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Cetuximab Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental: Pilot Phase 1b Combination with Cetuximab in NSCLC Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Cetuximab Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks
Experimental: Pilot Phase 1b Combination with Cetuximab in PDAC Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC)	Drug: MRTX849 MRTX849 will be administered orally once or twice daily in a continuous regimen Drug: Cetuximab Cetuximab will be administered as an intravenous infusion once per week or once every 2 weeks

Outcome Measures

Primary Outcome Measures

Characterize the safety of MRTX849 in patients having advanced solid tumor malignancies with KRAS G12C mutation [20 months]
Number of participants with treatment related adverse events
Evaluate the pharmacokinetics of MRTX849 [20 months]
Blood plasma concentration
Evaluate clinical activity/efficacy of MRTX849 [20 months]
Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)

Secondary Outcome Measures

Establish maximum tolerated dose [12 months]
Number of participants with dose limiting toxicity
Characterize safety and tolerability of MRTX849 in combination with selected therapeutic agents [12 months]
Number of participants with dose limiting toxicity
Evaluate the pharmacokinetics of new MRTX849 oral formulations [6 months]
Blood plasma concentration
Evaluate the pharmacokinetics of MRTX849 administered with food [6 months]
Blood plasma concentration

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation
Unresectable or metastatic disease
Standard treatment is not available or patient declines; first-line treatment for NSCLC for certain cohorts
Adequate organ function

Exclusion Criteria:

History of intestinal disease or major gastric surgery or inability to swallow oral medications
Other active cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Alaska Oncology and Hematology	Anchorage	Alaska	United States	99508
3	Mayo Clinic in Arizona	Phoenix	Arizona	United States	85054
4	Arizona Oncology Associates	Tucson	Arizona	United States	85704
5	Kaiser Permanente-Bellflower Medical Offices	Bellflower	California	United States	90706
6	Beverly Hills Cancer Center	Beverly Hills	California	United States	90211
7	City of Hope	Duarte	California	United States	91010
8	St. Joseph Heritage Healthcare	Fullerton	California	United States	92835
9	University of California San Diego Moores Cancer Center	La Jolla	California	United States	92093
10	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92663
11	University of California, Irvine	Orange	California	United States	92868
12	California Cancer Associates for Research and Excellence	San Diego	California	United States	92111
13	Ridley - Tree Cancer Center - Santa Barbara	Santa Barbara	California	United States	93105
14	Kaiser Permanente	Vallejo	California	United States	94589
15	Rocky Mountain Cancer Centers	Aurora	Colorado	United States	80012
16	University of Colorado Hospital	Aurora	Colorado	United States	80045
17	SCL Health - Saint Joseph Hospital Cancer Center	Denver	Colorado	United States	80218
18	St. Mary's Hospital & Regional Medical Center - Research	Grand Junction	Colorado	United States	81501
19	Yale Cancer Center	New Haven	Connecticut	United States	06511
20	Medical Oncology Hematology Consultants	Newark	Delaware	United States	19713
21	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224
22	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida	United States	33140
23	Miami Cancer Institute Baptist Health	Miami	Florida	United States	33176
24	Mid Florida Hematology and Oncology Center	Orange City	Florida	United States	37263
25	Woodlands Medical Specialists	Pensacola	Florida	United States	32503
26	BRCR Medical Center	Plantation	Florida	United States	33322
27	University Cancer and Blood Center	Athens	Georgia	United States	30607
28	Northwest Georgia Oncology Centers, PC	Marietta	Georgia	United States	30060
29	Illinois Cancer Specialists - Niles	Niles	Illinois	United States	60714
30	University of Iowa Hospital & Clinics	Iowa City	Iowa	United States	52242
31	University of Kansas Medical Center	Westwood	Kansas	United States	66205
32	University of Kentucky	Lexington	Kentucky	United States	40536
33	Main Health Cancer Center Biddeford	Biddeford	Maine	United States	04005
34	Maryland Oncology Hematology-Columbia	Columbia	Maryland	United States	21044
35	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
36	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
37	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201
38	Henry Ford Medical Center	Detroit	Michigan	United States	48377
39	Minnesota Oncology	Minneapolis	Minnesota	United States	55102
40	University of Minnesota	Minneapolis	Minnesota	United States	55454
41	Mayo Clinic in Minnesota	Rochester	Minnesota	United States	55905
42	Metro-Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota	United States	55416
43	Central Care Cancer Center - Bolivar	Bolivar	Missouri	United States	65613
44	Goldschmidt Cancer Center- Central Region Medical Center	Jefferson City	Missouri	United States	65109
45	Frontier Cancer Center	Billings	Montana	United States	59102
46	Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
47	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
48	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89169
49	Roswell Park	Buffalo	New York	United States	14263
50	Perlmutter Cancer Center	New York	New York	United States	10016
51	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
52	University of North Carolina	Chapel Hill	North Carolina	United States	27514
53	FirstHealth Outpatient Cancer Center	Pinehurst	North Carolina	United States	28374
54	The Christ Hospital Cancer Center	Cincinnati	Ohio	United States	45219
55	University of Cincinnati Health Barrett Cancer Center	Cincinnati	Ohio	United States	45219
56	Cleveland Clinic	Cleveland	Ohio	United States	44195
57	OSU Medical Center	Columbus	Ohio	United States	43210
58	Kettering Cancer Center	Kettering	Ohio	United States	45429
59	Willamette Valley Cancer Institute and Research Center - Eugene	Eugene	Oregon	United States	97401
60	Lehigh Valley Heath	Allentown	Pennsylvania	United States	18103
61	Penn State Health Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033
62	Charleston Oncology P.A.	Charleston	South Carolina	United States	29414
63	Medical University of South Carolina	Charleston	South Carolina	United States	29425
64	Tennessee Oncology/The Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
65	Texas Oncology-Arlington	Arlington	Texas	United States	76014
66	USOR - Texas Oncology - Austin Central	Austin	Texas	United States	78731
67	Mary Crowley Cancer Research	Dallas	Texas	United States	75231
68	Texas Oncology at Presbyterian Dallas	Dallas	Texas	United States	75231
69	USOR Texas Oncology Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
70	Texas Oncology	Fort Worth	Texas	United States	76104
71	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
72	South Texas Accelerated Research Therapeutics	San Antonio	Texas	United States	78229
73	Texas Oncology	Sugar Land	Texas	United States	77479
74	Texas Oncology	Tyler	Texas	United States	75702
75	Texas Oncology Waco	Waco	Texas	United States	76712
76	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
77	Virginia Oncology Associates-Newport News	Newport News	Virginia	United States	23606
78	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
79	USOR - Compass Oncology - Vancouver	Vancouver	Washington	United States	98684
80	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin	United States	53792
81	PanOncology Trials	San Juan		Puerto Rico	00935