Inclusion Criteria: Subject has provided informed consent prior to initiation of any study specific activities/procedures Men or women greater than or equal to 18 years old Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12Cmutation identified through DNA sequencing. Subjects must have received prior standard therapy appropriate for their tumor type and stage of disease, or in the opinion of the Investigator, would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard of care therapy. Part 1 (Dose Exploration) - Subjects willing to provide archived tumor samples (fresh frozen sample or formalin fixed, paraffin embedded [FFPE] sample collected within 5 years) or willing to undergo pretreatment tumor biopsy. Part 2 (Dose Expansion) - Willing to undergo pre-treatment tumor biopsy. Subjects can be allowed to enroll without undergoing tumor biopsy upon agreement with Investigator and the Medical Monitor if tumor biopsy is not feasible. Measurable or evaluable disease per RECIST 1.1 criteria (Appendix D). Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 2 Life expectancy of greater than 3 months, in the opinion of the investigator Ability to take oral medications and willing to record daily adherence to investigational product QTc less than or equal to 470 msec (based on average of screening triplicates) Adequate hematological laboratory assessments, as follows: Absolute neutrophil count (ANC) greater than or equal to 1.5 x 109/L Platelet count greater than or equal to 75 x 109/L Hemoglobin greater than or equal to 9 g/dL Adequate renal laboratory assessments, as follows: Estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation greater than or equal to 60 ml/min/1.73 m2 Adequate hepatic laboratory assessments, as follows: AST less than 2.5 x ULN (if liver metastases are present, less than or equal to 5 x ULN) ALT less than 2.5 x ULN (if liver metastases are present, less than or equal to 5 x ULN) Alkaline phosphatase less than 2.0 x ULN (if liver or bone metastases are present, less than 3.0 x ULN) Total bilirubin less than 1.5 x ULN (less than 2.0 x ULN for subjects with documented Gilbert's syndrome or less than 3.0 x ULN for subjects for whom the indirect bilirubin level suggests an extrahepatic source of elevation) Adequate coagulation laboratory assessments, as follows: Prothrombin time (PT) or partial thromboplastin time (PTT) less than 1.5 x upper limit of normal (ULN), OR International normalized ratio (INR) less than 1.5 or within target range if on prophylactic anticoagulation therapy. Subject able to eat a standardized high-fat, high-caloric meal within 25 minutes Subject able to fast for greater than or equal to10 hours Subject able to handle collection of his/her urine over a 24 hour period. Pathologically documented, definitively diagnosed KRAS p.G12Cmutant NSCLC Pathologically documented, and definitively diagnosed KRAS p.G12C mutant CRC Exclusion Criteria: Active brain metastases from non-brain tumors. Subjects who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade less than or equal to 2; b) on stable doses of dexamethasone, if applicable; and c) follow-up MRI shows no new lesions appearing History or presence of hematological malignancies unless curatively treated with no evidence of disease Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association greater than class II), unstable angina, or cardiac arrhythmia requiring medication Gastrointestinal (GI) tract disease causing the inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, uncontrolled inflammatory GI disease (eg, Crohn's disease, ulcerative colitis) Active infection requiring intravenous (IV) antibiotics within 1 weeks of study enrollment (day 1) Positive Hepatitis B Surface Antigen (HepBsAg) (indicative of chronic Hepatitis B), positive Hepatitis total core antibody with negative HepBsAg (suggestive of occult hepatitis B) or detectable Hepatitis C virus Ribonucleic acid (RNA) by PCR (indicative of active Hepatitis C - screening is generally done by Hepatitis C Antibody (HepCAb), followed by Hepatitis C virus RNA by PCR if HepCAb is positive) Known positive test for HIV Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1, or to levels dictated in the eligibility criteria with the exception of alopecia (Grade 2 or 3 toxicities from prior anti-tumor therapy that are considered irreversible [defined as having been present and stable for greater than 6 months], such as ifosfamide-related proteinuria, may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor) Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy [except for subjects with breast cancer], or investigational agent) within 28 days of study day 1; concurrent use of hormone deprivation therapy for hormone-refractory prostate cancer or breast cancer is permitted Therapeutic or palliative radiation therapy within 2 weeks of study day 1 Currently enrolled in another investigational device or drug study, or less than 28 days since ending another investigational device or drug study(s), or receiving other investigational agent(s) Other investigational procedures are excluded All herbal medicines (eg, St. John's wort), vitamins, and supplements consumed by the subject within the 30 days prior to receiving the first dose of AMG 510, and continuing use if applicable, will be reviewed by the Principal Investigator and the Amgen Medical Monitor. Written documentation of this review and Amgen acknowledgment is required for subject participation Major surgery within 28 days of study day 1 Men and women of reproductive potential who are unwilling to practice acceptable methods of effective birth control while on study through 1 week (women) or 90 days (men) after receiving the last dose of study drug. Acceptable methods of effective birth control include sexual abstinence (refraining from heterosexual intercourse; men, women); vasectomy; tubal ligation; or a condom with spermicide (men) in combination with barrier methods, hormonal birth control or IUD (women) Women who are lactating/breast feeding or who plan to breastfeed while on study through 1 week after receiving the last dose of study drug. Women with a positive pregnancy test. Women planning to become pregnant while on study through 1 week after receiving the last dose of study drug Subject has known sensitivity to any of the products to be administered during dosing Subject will not be available for protocol-required study visits or procedures, to the best of the subject and investigator's knowledge Subject has any kind of disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or to comply with all required study procedures History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion Use of known cytochrome P450 (CYP) 3A4 sensitive substrates (with a narrow therapeutic window), within 14 days or 5 half-lives (whichever is longer) of the drug or its major active metabolite, whichever is longer, prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor Use of strong inhibitors of CYP3A4 or P-gp within 14 days or 5 half-lives (whichever is longer) or grapefruit juice or grapefruit containing products within 7 days prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor. Use of strong inducers of CYP3A4 within 14 days or 5 half-lives (whichever is longer) within 7 days prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor. |
