Lung Cancer Clinical Trials

• A patient must meet all of the following inclusion criteria to be eligible to participate in this study.

• Advanced or metastatic solid tumor malignancy that has progressed or was non responsive to available therapies and for which no standard or available curative therapy exists.

∙ Triple negative breast cancer (TNBC) cohort: histologically or cytologically confirmed TNBC per American Society for Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, based on the most recent analyzed biopsy or other pathology specimen.

‣ Small cell lung cancer (SCLC) cohort: histologically or cytologically confirmed relapsed/refractory SCLC.

‣ Retinoblastoma 1 (RB1)-altered solid tumor cohort: solid tumors harboring a documented RB1 genomic alteration or Rb protein LoF, as identified through assays performed at Clinical Laboratory Improvement Amendments (CLIA)-certified or other similarly certified laboratories.

• Patients must have measurable disease by RECIST v1.1.

• Age ≥ 12 years and at least 40 kg in body weight.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (patients ≥ 18 years of age), Karnofsky performance status ≥ 70% (patients ≥ 16 to \< 18 years of age), or Lansky performance status ≥ 70% (patients \< 16 years of age). Patients who are unable to walk because of paralysis, but who can sit in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score (Appendix 1).

• Life expectancy \>12 weeks.

• For patients ≥ 18 years of age: able to undergo a fresh biopsy if medically feasible.

• Ability to swallow capsules by mouth.

• Have the following laboratory values:

∙ For patients ≥ 18 years of age: calculated CrCl ≥ 60 mL/min/1.73 m2 by Cockroft-Gault formula (actual body weight must be used for CrCl unless BMI \> 30 kg/m2 then lean or ideal body weight must be used based on institutional practice), or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 based alternative methods of determination (e.g., modification of diet in renal disease \[MDRD\], 24-hour urine collection) if consistent with local or institutional practice. For patients \< 18 years of age: serum creatinine within normal limits (as defined below) or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2 based on local institutional practice for determination.

∙ Age at Screening Maximum Serum Creatinine SI Unit age 12 to \< 15 years - 0.81 mg/dL; age 15 to \< 18 years (male) - 1.08 mg/dL; age 15 to \< 18 years (female) - 0.84 mg/dL

‣ Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome with Sponsor Medical Monitor approval.

‣ Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN, or ≤ 5 × ULN if due to liver involvement by tumor.

‣ Hemoglobin ≥ 9.0 g/dL (last transfusion \> 14 days prior to first dose of study drug).

‣ Platelets ≥ 100 × 10\^9 cells/L (last platelet transfusion \> 14 days prior to first dose of study drug).

‣ Absolute neutrophil count ≥ 1.2 ×10\^9 cells/L (last dose of hematopoietic growth factors \> 14 days from first dose of study drug).

• Females of childbearing potential must commit to sexual abstinence or to use two acceptable forms of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives) for the duration of the study and for four months following the last dose of study treatment. Females who are at least two years postmenopausal or premenopausal with documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or permanent infertility due to alternate medical causes other than above are not considered females of childbearing potential. Male patients must be sterile (biologically or surgically), commit to sexual abstinence or to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for four months following the last dose of study treatment.

⁃ Females of childbearing potential must have a negative serum pregnancy test during Screening and a negative urine or serum test prior to receiving first dose of study drug. Females who are at least two years postmenopausal or premenopausal with documented hysterectomy, bilateral salpingectomy, bilateral oophorectomy, or permanent infertility due to alternate medical causes other than above are not considered females of childbearing potential.

⁃ Signed and dated IRB/EC-approved ICF for potential patients ≥ 18 years of age. A signed and dated IRB/EC-approved adolescent assent form may also be required for patients 12 to 17 years of age in addition to an ICF signed by a parent or legal guardian.