Phase Ib Trial of the KRAS G12C Inhibitor Adagrasib (MRTX849) in Combination With the PARP Inhibitor Olaparib in Patients With KRAS G12C Mutated Advanced Solid Tumors, With a Focus on Gynecological, Breast, Pancreatic and KEAP1 Mutated Non-small Cell Lung Cancers

NCT06130254 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 2022-0136NCI-2023-09685
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluate safety and tolerability, while establishing the recommended dose of the investigational drug combination of adagrasib and olaparib that can be given to participants with advanced solid tumor(s) with a KRAS G12C and/or KEAP1 mutation.

Conditions

Advanced Solid Tumor; Non-small Cell Lung Cancers

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  through study completion; an average of 1 year.

Study Arms (1)

Adagrasib+Olaparib

EXPERIMENTAL

Participants will take adagrasib and olaparib by mouth 2 times each day. Each dose should be taken at about 12 hours apart (1 dose in the morning, 1 dose in the evening). The study drugs should be swallowed whole with water. Do not chew, crush, dissolve, or divide the study drugs. If forget a dose and less than 2 hours have passed since the usual time participants take the study drug, take the dose as soon as participants remember. If more than 2 hours have passed, do not take the dose. Wait and take the next dose as scheduled

Drug: Adagrasib; Drug: Olaparib

Interventions

Olaparib DRUG

Given by PO BID

Also known as: Lynparza™

Adagrasib+Olaparib

Adagrasib DRUG

Given by PO BID

Also known as: MRTX849

Adagrasib+Olaparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Dose escalation cohort: Histologically confirmed diagnosis of a solid tumor malignancy with a KRAS G12C mutation. Participants are eligible based on detection of these mutations in tumor tissue or plasma circulating tumor DNA (ctDNA) with a minimum VAF of 1%.
• Dose expansion cohort 1: Histologically confirmed diagnosis advanced pancreatic cancer with KRAS G12C mutation. Participants must have progressed on at least 1 prior line of standard systemic therapy and must be eligible based on detection of KRAS G12C mutation in tumor tissue or ctDNA with a minimum VAF of 1%.
• Dose expansion cohort 2: Histologically confirmed diagnosis of advanced breast cancer with KRAS G12C mutation. Participants must have progressed on at least 1 prior line of standard systemic therapy and must be eligible based on detection of KRAS G12C mutation in tumor tissue or ctDNA with a minimum VAF of 1%.
• Dose expansion cohort 3: Histologically confirmed diagnosis of advanced uterine or epithelial ovarian cancer with KRAS G12C mutation. Participants must have progressed on at least 1 prior line of standard systemic therapy and must be eligible based on detection of KRAS G12C mutation in tumor tissue or ctDNA with a minimum VAF of 1%.
• Dose expansion cohort 4: Histologically confirmed diagnosis of NSCLC with KRAS G12C and KEAP1 co-mutations. Participants must have progressed on at least 1 prior line of standard systemic therapy and must be eligible based on detection of KRAS G12C and KEAP1 co-mutations in tumor tissue or plasma circulating tumor DNA (ctDNA) with a minimum VAF of 1%.
• Unresectable or metastatic disease and for which standard curative or palliative measures do not exist or are no longer effective.
• Participants must have evaluable or measurable disease per RECIST v1.1 for the dose escalation cohort and must have measurable disease per RECIST v1.1 for dose expansion cohorts 1-4.
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Life expectancy of at least 3 months.
• Most recent prior systemic therapy (e.g., chemotherapy, immunotherapy or, investigational agent) and radiation therapy discontinued at least 2 weeks before first dose date.
• Eastern Cooperative Oncology Group (ECOG) performance status in 0 or 1 (see Appendix 1).
• Laboratory values within the screening period:
• Absolute neutrophil count ≥ 1.5 x 109/L
• Platelet count ≥ 100,000/mm3 (≥ 100 x 109/L)
• Hemoglobin ≥ 10 g/dL, in the absence of transfusions for at least 28 days

You may not qualify if:

• Participants presenting with any of the following will not be included in the study:
• Active brain metastases. Patients are eligible if brain metastases are adequately treated and patients are neurologically stable (which is assessed in a case-by-case by the treating physician based on the likelihood of central nervous system (CNS) activity - except for residual signs or symptoms related to the CNS treatment- and by the lack of corticosteroid dosing or by having a stable or decreasing dose of ≤ 10 mg daily prednisone, or equivalent) for at least 2 weeks prior to enrollment.
• Participants with carcinomatous meningitis.
• Participants with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1), excluding alopecia.
• History of significant hemoptysis or hemorrhage within 4 weeks of the first dose date.
• Undergone major surgery within 4 weeks of first dose date, or not recovered from any major surgery that occurred \>2 weeks before starting study treatment.
• Undergone allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
• History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions (e.g., uncontrolled nausea, vomiting, malabsorption syndrome) likely to alter absorption of study treatment or result in inability to swallow oral medications.
• Any of the following cardiac abnormalities:
• Unstable angina pectoris or myocardial infarction within 6 months prior to enrollment
• Congestive heart failure NYHA ≥ Class 3 within 6 months prior to enrollment
• Left ventricular ejection fraction (LVEF) \< 50%
• QTc \> 480 milliseconds or medical or immediate family history of congenital Long QT Syndrome
• Symptomatic or uncontrolled atrial fibrillation or other arrhythmia within 6 prior to enrollment

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Mirati Therapeutics Inc.: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Interventions

adagrasib; olaparib

Study Officials

• Timothy Yap, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: November 14, 2023
• Study Start: January 30, 2024
• Primary Completion: June 14, 2024
• Study Completion: March 30, 2026
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (1)