New combo therapy targets hard-to-treat lung cancer mutation

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Age ≥ 18 years old * Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 at the time of study treatment initiation * Have pathologically (cytology or histology) confirmed diagnosis of NSCLC. Non-small cell carcinoma diagnosis without specific tissue of origin confirmation may be eligible with approval from primary investigator (PI) review * Must be eligible for treatment with standard of care KRAS G12C inhibitors * Documented KRAS G12C mutation. Testing will occur by standard of care next generation sequencing (NGS) testing and results will be available in the medical record * Have at least 6-month life expectancy * Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L * Platelets ≥ 70 x 10\^9/L * Hemoglobin ≥ 9 g/dL * Plasma creatinine ≤ 1.5 x institution upper limit of normal (ULN) * ALT (alanine aminotransferase) and aspartate aminotransferase (AST) ≤ 3 x ULN (ALT and AST ≤ 5 x ULN is acceptable if liver metastases are present) * Total plasma bilirubin ≤ 1.5 x ULN. For patients with well documented Gilbert's syndrome, total bilirubin ≤ 3 x ULN with direct bilirubin within normal range * Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 * Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately * Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure * Participant agrees to provide blood samples at the start of treatment and at multiple times during the study as well as research specimen allocation at the time of standard of care rebiopsy at the time of disease progression Exclusion Criteria: * Receipt of anticancer chemotherapy within 4 weeks before the first administration of study drug (see exception allowed for #2) * Previously treated with KRAS G12C inhibitor (exception allowed for patients who started KRAS G12C inhibitor within 4 weeks of study enrollment) * Prior radiotherapy or gamma knife within 2 weeks of study treatment for non-brain metastasis. Subjects must have recovered from all radiation related toxicities * Active/untreated brain metastasis. Whole brain radiation or gamma knife radiosurgery performed less than 2 weeks prior to first administration of study drug. Previously treated brain metastasis allowed as long as not requiring steroids * Leptomeningeal involvement regardless of treatment status * Active, clinically serious infections or other serious uncontrolled medical conditions (exception allowed: patients taking prophylactic anti-viral, anti-fungal or antibiotics. Patients on long-term treatment for acid-fast or fungal organisms must have been on stable dosing of ant-infective regimen for at least 4 weeks of uninterrupted treatment and without associated common toxicity criteria (CTC) grade 2 or higher drug-related lab abnormalities within 4 weeks of study enrollment) * Had major surgery within 14 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered major surgery) resulting from a prior surgery * Currently receiving or has received systemic corticosteroids within 4 weeks prior to starting study drug for management of brain metastases, or who have not fully recovered from side effects of such treatment. Steroids for endocrine replacement or receipt of short course of steroids during this preceding 4-week period as supportive medication such as for drug allergy, anti-emetic, etc. is allowed * Pregnant or nursing female participants * Patients diagnosed with a secondary invasive cancer within 2 years prior to starting protocol therapy with the following exceptions: non-melanoma skin cancers, in-situ cancers, and prostate cancer Gleason ≤ to 6 (under surveillance or treated), early-stage node-negative estrogen receptor (ER) +/ progesterone receptor (PR) + breast cancer with Oncotype Dx score \< 25 (adjuvant hormonal therapy allowed) * History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator, including, but not limited to: * Myocardial infarction or arterial thromboembolic events within 30 days prior to enrollment or with severe or unstable angina, New York Heart Association (NYHA) Class III or IV disease * Patient has known hypersensitivity to the components of the study drugs or any analogs