A phase Ib/II trial of AMG 655 and panitumumab (pmab) for the treatment (tx) of metastatic colorectal cancer (mCRC): Safety results

4130^ Introduction: Pmab is a fully human antibody targeting the epidermal growth factor receptor that is approved as monotherapy for mCRC in the US, EU, and Canada. AMG 655 is an investigational, fully human agonistic antibody against death receptor 5. This is the first study to evaluate the safety, tolerability, and efficacy of AMG 655 and pmab for the tx of mCRC. Methods: Eligible patients (pts) were ≥ 18 years old, had ECOG status 0–1, radiographic disease progression (PD) during or after tx with fluoropyrimidine, irinotecan, and/or oxaliplatin chemotherapy for mCRC. This is a 2-part study: in part 1 (n∼6–27 pts), the primary endpoint is the incidence of dose-limiting toxicities (DLTs); in part 2 (n∼38–41 pts), the primary endpoint is objective response rate per modified RECIST. Secondary endpoints for both parts include efficacy, pharmacokinetics (PK), and antibody formation. In part 1, pts received pmab 6 mg/kg Q2W plus AMG 655 at a starting dose of 10 mg/kg (evaluation of subsequent doses of 3 mg/kg or 1 mg/kg if needed; 6–9 pts at each dose) by sequential intravenous infusion at week 1 and Q2W thereafter until PD or intolerability. The tolerable dose in part 1 was selected for part 2. Results: We describe here the safety of the first 15 pts (n=5 part 1; n=10 part 2) after ≥ 8 weeks on study. Eight (53%) pts were women, 14 (93%) pts were white, and 9 (60%) pts had ECOG 1. Median (range) age was 61 (38–77) years. All pts received pmab 6 mg/kg and AMG 655 10 mg/kg Q2W. Median (range) follow-up time was 15.4 (9–31) weeks. There were no DLTs in part 1, thus AMG 655 10 mg/kg Q2W was selected for part 2. One (7%) pt had a tx-related adverse event (AE) ≥ grade (gr) 3: gr 3 hypomagnesemia. Tx-emergent Aes ≥ 25% are shown ( Table ). Laboratory values ≥ gr 3: one gr 3 AST and ALT; one gr 3 lipase. From intensive PK samples from the first 6 pts, pmab had no apparent impact on the PK of AMG 655. Conclusions: AMG 655 and pmab can be safely combined in later lines of tx for mCRC. The study is ongoing. Safety results for additional pts will be presented. [Table: see text] [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .

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