A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 510 Monotherapy in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation and AMG 510 Combination Therapy in Subjects With Advanced NSCLC With KRAS p.G12C Mutation (Codebreak 100)
Evaluate the safety and tolerability of AMG 510 in adult patients with KRAS p.G12C mutant advanced solid tumors. Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult patients with KRAS p.G12C mutant advanced solid tumors.
Participating only in Phase II; Phase II Primary Objectives To evaluate tumor objective response rate (ORR), assessed by RECIST 1.1 criteria, of AMG 510 as monotherapy in subjects with KRAS p.G12C mutant advanced solid tumors(NSCLC, colorectal cancer [CRC], and other tumor types). Secondary Objectives: To evaluate other measures of AMG 510 efficacy as monotherapy in subjects with
KRAS p.G12C mutant advanced solid tumors by RECIST 1.1 (NSCLC, CRC, and other
tumor types): Duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS), PFS rate at 6 months and 12 months, OS rate at 12 months. To evaluate the safety and tolerability of AMG 510 in adult subjects with KRAS p.G12C mutant advanced solid tumors (NSCLC, CRC, and other tumor types). To evaluate the PK of AMG 510 following administration as an oral tablet formulation.
Men or women greater than or equal to 18 years old.
Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12Cmutation identified through molecular testing.
For NSCLC: Phase 1 patients must have received platinum-based combination therapy AND/OR targeted therapies (ie, if molecular testing has identified mutations in EGFR, ALK, or proto-oncogene tyrosine-protein kinase ROS [ROS1] or expression of programmed death-ligand [PD-L1]), prior to receiving AMG 510. Phase 2 Part A patients must have progressed after receiving anti-PD1 or anti-PD-L1 immunotherapy (unless contraindicated) AND/OR platinum-based combination chemotherapy AND targeted therapy if actionable oncogenic driver mutations were identified (ie, EGFR, ALK, and ROS1). Patients in phase 2 Part A must have received no more than 3 prior lines of therapy. For all NSCLC patients, the following guidance should be used: (*) Adjuvant therapy will count as a line of therapy if the patient progressed on or within 6 months of adjuvant therapy administration. (*) In locally advanced and unresectable NSCLC, disease progression on or within six months of end of prior curatively intended multimodal therapy will count as a line of therapy. If chemoradiation is followed by planned systemic therapy without documented progression between chemoradiation and systemic therapy, the entire treatment course counts as 1 line of therapy. (*) Maintenance therapy following platinum doublet-based chemotherapy is not considered as a separate line of therapy.
Patients willing to provide archived tumor tissue samples (formalin fixed, paraffin embedded [FFPE] sample collected within 5 years) or willing to undergo pretreatment tumor biopsy. Phase 1 patients with all tumor types and phase 2 patients with tumor types other than NSCLC or CRC with prior molecularly confirmed KRAS p.G12C mutation who do not have archived tissue available can be allowed to enroll without undergoing tumor biopsy upon agreement with investigator and the Medical Monitor if a tumor biopsy is not feasible
Participants who have lesions that can be feasibly biopsied will be asked to undergo an additional biopsy at the time of tumor progression
Measurable disease per RECIST 1.1 Criteria
Ability to take oral medications and willing to record daily adherence to investigational product utilizing sponsor-provided dosing diary
Adequate hematological, renal and hepatic laboratory assessments, as defined per protocol.
Adequate coagulation laboratory assessments, as defined per protocol.
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