Ipatasertib in Combination with Docetaxel for the Treatment of Non-small Cell Lung Cancer

Inclusion Criteria

• Ability of participant OR legally authorized representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
• Life expectancy >= 12 weeks
• Males and females age >= 18 years
• Allowable type and amount of prior therapy: First line anti-PD1/PD-L1, either single agent or in combination with chemotherapy or anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Diagnoses of advanced/metastatic non-small cell lung cancer (NSCLC) and have failed or are intolerant to first line anti-PD1/PD-L1, either single agent or in combination with chemotherapy, and/or anti-CTLA4
• Patients who were treated with concurrent chemoradiation therapy followed by durvalumab, upon progression on or after durvalumab, will be eligible if there is no other systemic anticancer treatment
• Patients who are qualified for first line Food and Drug Administration (FDA)-approved targeted therapy due to the presence of driver mutation (e.g. EGFR, ALK, BRAF, ROS1, etc.) may be eligible if they have failed at least one line of such targeted therapy, followed by the failure or intolerance to only 1 line of antiPD1/PD-L1 therapy, either single agent or in combination with chemotherapy and/or antiCTLA4
• Patients who harbor a driver mutation but not yet qualified for first line FDA-approved targeted therapy (e.g. KRAS G12C, HER2, etc.) may be eligible even if they have received targeted therapy but ONLY in the following settings: 1) received targeted therapy in the first line setting (e.g. from a trial), followed by the failure or intolerance to only 1 line of anti-PD1/PD-L1 therapy, either single agent or in combination with chemotherapy and/or anti-CTLA4; 2) received targeted therapy in combination with anti-PD1/PD-L1 in the 1st line setting (e.g. from a trial), with or without chemotherapy or anti-CTLA-4
• Leukocytes >= 3,000/ul
• Absolute neutrophil count >= 1,500/ul
• Platelets >= 100,000/ul
• Hemoglobin >= 9 g/dL
• Serum creatinine clearance (CL) > 50 mL/min by the Cockcroft-Gault formula
• Total bilirubin =< 1.5 x upper limit of normal (ULN) – (Patients with known Gilbert disease who have serum bilirubin =< 3 x ULN may be enrolled.)
• Aspartate aminotransferase (AST) =< 1.5 x institutional upper limit – (Patients with liver metastasis may have AST =< 2.5 x ULN [and total bilirubin =< 1.5 x ULN])
• Alanine aminotransferase (ALT) =< 1.5 x institutional upper limit – (Patients with liver metastasis may have ALT =< 2.5 x ULN [and total bilirubin =< 1.5 x ULN])
• Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence, or to use an acceptable form of contraception for the duration of study participation, and for 90 days following completion of therapy
• Men of child-bearing potential must agree not to donate sperm while on this study and for 90 days after their last study treatment.
• If women are not of child bearing potential, indicate the applicable reason below: * Has undergone a hysterectomy or bilateral oophorectomy * Has been naturally postmenopausal for at least 12 consecutive (i.e., has had menses at any time in the preceding 12 consecutive 12 months) and is > 45 years of age. OR list type of contraception to be used

Exclusion Criteria

• Concurrently enrolled in another clinical study, unless it is an observational (non-interventional) clinical study or if the participant is in the follow-up period of an interventional study
• Currently on or is not anticipated to use other investigational agents within 14 days prior to and while participating in this study
• Does not have mixed small cell and non-small cell lung cancer histology
• Does not have any unresolved toxicity Common Terminology Criteria for Adverse Events (CTCAE) > grade 2 from the prior 1st immunotherapy. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study drug may be included (e.g., hearing loss)
• Patients who have targetable mutations that qualify for targeted therapy (e.g. mutations of EGFR, BRAF, ALK, ROS1, NTRAK) will be excluded from this study.
• Is not on concomitant therapy intended for the treatment of cancer (including, but not limited to, chemotherapy, hormonal therapy, immunotherapy, radiotherapy, and herbal therapy) for 14 days prior to starting study treatment, depending on the agent and during study treatment, until disease progression is documented and the patient has discontinued study treatment, with the exception of palliative radiotherapy and local therapy per principal investigator (PI) discretion.
• Has not had recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of study drug
• Have uncontrolled brain metastasis. Patients have asymptomatic or controlled brain metastasis by surgery or radiation, with the requirement of steroids no more than prednisone 10mg daily or its equivalent dose will be eligible
• Does not have history of allergy to taxanes
• Does not have history of leptomeningeal carcinomatosis
• Does not have recent history of myocardial infarction (MI) or symptomatic coronary artery disease within 6 months of screening
• Is not receiving active therapy for human immunodeficiency virus (HIV), hepatitis B or hepatitis C
• Does not have history of malabsorption syndrome or other condition that would interfere with enteral absorption or results in the inability or unwillingness to swallow pills
• Does not have history of type I or type II diabetes mellitus requiring insulin (patients who are on a stable dose of oral diabetes medication >= 2 weeks prior to initiation of study treatment)
• Does not have grade >= 2 uncontrolled or untreated hypercholesterolemia or hypertriglyceridemia
• Does not have history of or active inflammatory bowel disease (e.g., Crohn's disease and ulcerative colitis) or active bowel inflammation (e.g., diverticulitis)
• Have active pneumonitis that requires systemic immunosuppressants. Patients who are recovering (e.g. from immune-mediated pneumonitis) and on steroids as the only immunosuppressant with prednisone no more than 10 mg daily or its equivalent dose are eligible based on investigator’s clinical discretion
• Does not have history of lung disease: interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)
• Does not have active ventricular arrhythmia requiring medication and/or urgent care
• Does not have psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent
• Is not pregnant, breast feeding or planning to become pregnant while receiving study treatment or for less than 90 days after the last dose of study treatment
• For males with partners of childbearing potential, is not planning to father a child or donate sperm while receiving study treatment or for less than 90 days after the last dose of study treatment.
• Does not have any condition that, in the opinion of the investigator, would interfere with evaluation or interpretation of patient safety or study results