A Phase 1/2 of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation

Program Status

Active, not recruiting

Phase

Phase 1

Prior Immunotherapy Allowed

Yes

CRC-directed Trial

Yes

Drugs

MRTX1133

Tags

MSI-H/ MMRd, MSS/ MMRp

Comments

Trial with an oral, novel KRASG12D inhibitor. Expansion cohorts in pancreatic, colorectal, lung and other KRASG12D tumor types. Only for patients with unresectable or metastatic disease.

“MRTX1133 is a highly potent investigational inhibitor of the KRASG12D driver mutation and demonstrated selective and reversible inhibition of KRASG12D in both its active and inactive states.  In addition, MRTX1133 administration resulted in marked tumor response in preclinical KRASG12D mutated pancreatic cancer models as well as lung and colorectal cancer models. MRTX1133 has demonstrated favorable properties including a low risk for off-target activity and drug interactions and a predicted human half-life of greater than 50 hours.”

Location Location Status
United States
Local Institution - 311
Phoenix, Arizona 85054
Active, not recruiting
Local Institution - 309
New Haven, Connecticut 06520 8028
Active, not recruiting
Local Institution - 301
Lady Lake, Florida 32159 8987
Active, not recruiting
Local Institution - 306
Baltimore, Maryland 21231
Active, not recruiting
Local Institution - 308
Boston, Massachusetts 02114 3117
Active, not recruiting
Local Institution - 310
Boston, Massachusetts 02215
Active, not recruiting
Local Institution - 314
Grand Rapids, Michigan 49546
Active, not recruiting
Local Institution - 312
New York, New York 10065 6800
Active, not recruiting
Local Institution - 303
Nashville, Tennessee 37203
Active, not recruiting
Local Institution - 302
Houston, Texas 77030
Active, not recruiting
Local Institution - 304
San Antonio, Texas 78229 3307
Active, not recruiting
Local Institution - 313
San Antonio, Texas 78229
Active, not recruiting
Local Institution - 305
Fairfax, Virginia 22031
Active, not recruiting
Local Institution - 307
Seattle, Washington 98109 1023
Active, not recruiting

Inclusion Criteria

Inclusion Criteria:

* Histologically confirmed diagnosis of a solid tumor malignancy harboring KRAS G12D mutation in tumor tissue or ctDNA.
* Unresectable or metastatic disease.
* Patients must have received standard therapies appropriate for their tumor type and stage; first-line treatment for PDAC for certain cohorts.
* Presence of tumor lesions to be evaluated per RECIST v1.1:

1. in the Phase 1 dose escalation cohorts, patients must have measurable or evaluable disease.
2. in the Phase 1b and Phase 2 cohorts, patients must have measurable disease.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Adequate organ function.
* Age ≥ 18 years

Exclusion Criteria

Exclusion Criteria:

* Active brain metastases or carcinomatous meningitis.
* Prior treatment with a KRAS G12D inhibitor (Phase 1b & Phase 2 only).
* History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of study treatment.
* History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow oral medications.
* History of malignant small bowel obstruction.
* Cardiac abnormalities.

NCT ID

NCT05737706

Date Trial Added

2023-02-21

Updated Date

2025-01-09