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Clinical Trial 20304

Cancer Type: Thoracic
Study Type: Treatment
NCT#: NCT03600883

Phase: Phase I/II
Prinicipal Investigator:

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Overview

Study Title

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)

Summary

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.

Objective

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.

Treatments

Therapies

Medications

AMG 510 (); Pembrolizumab (Keytruda)

Inclusion Criteria

Inclusion Criteria:

  • 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 patients must have progressed after receiving anti-PD1 or anti-PD-L1 immunotherapy (unless contraindicated) AND/OR platinum-based combination chemotherapy. If actionable oncogenic driver mutations were identified (ie, EGFR, ALK, and ROS1), subjects must have received no more than 3 prior lines of therapy. For all NSCLC subjects, the following guidance should be used: (*) Adjuvant therapy will count as a line of therapy if the subject 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 subjects 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.
  • Other criteria apply

  • Exclusion Criteria

    Exclusion Criteria:

  • Active brain metastases from non-brain tumors.
  • History or presence of hematological malignancies unless curatively treated with no evidence of disease >-= 2 years.
  • Myocardial infarction within 6 months of study day 1.
  • Gastrointestinal (GI) tract disease causing the inability to take oral medication.
  • Active infection requiring IV antibiotics within 1 week of study day 1.
  • Exclusion of hepatitis infection based on the results and criteria outlined per protocol.
  • Known positive test for HIV
  • Unresolved toxicities from prior anti-tumor therapy
  • Anti-tumor therapy 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. Patients must have recovered from all radiotherapy related toxicity.
  • Currently enrolled in another investigational device or drug study, or less than 28 days since ending another investigational device or drug study or receiving other investigational agents.
  • Other exclusions apply

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