Exhibit 10.1

Confidential

AMENDMENT – NUMBER ONE

AGREEMENT

This Amendment Number One (this “Amendment 1”) is effective as of July 2, 2009 by and between Antigenics Inc., a Delaware corporation, having its principle place of business at 3 Forbes Road, Lexington, Massachusetts 02421, USA (the “Company”) and Garo Armen (the “Executive”). Capitalized terms not otherwise defined herein shall have the meaning set forth in the Agreement (defined below).

WITNESSETH

WHEREAS, the parties have entered into an Agreement effective as December 1, 2005 setting forth employment terms (the “Agreement”); and

WHEREAS, the parties now wish to amend the Agreement to reflect certain changes in the Company’s Executive Change in Control Plan as set forth herein;

NOW, THEREFORE, the parties agree as follows:

(i) if a Change of Control occurs on the date of such Change in Control, fifty-percent (50%) of any (A) outstanding unvested stock options or (B) shares of unvested restricted stock of the Company, granted or issued to the Executive as of the date of the Change in Control shall become vested, exercisable and, in the case of shares of restricted stock, no longer subject to forfeiture, provided that the Executive is employed by the Company on the date of such Change in Control.

(ii) if a Change of Control occurs and within twenty-four (24) months following such Change of Control, the Company terminates the Executive’s employment other than for Cause, or the Executive terminates his employment for Good Reason, then, in lieu of any payments to or on behalf of the Executive under Section 5.d or 5.e hereof, the Company shall pay to the Executive in one lump sum an amount equal to (A) twenty-four (24) months Base Salary at the rate in effect on the date of termination. plus (B) two times the higher of (x) the Executive’s target incentive bonus under the Executive Incentive Plan for the year in which the Executive’s employment is terminated or (y) the actual incentive bonus paid to the Executive, if any, under the Executive Incentive Plan for the last full fiscal year preceding the year in which the Executive’s employment is terminated; and shall also, until the conclusion of a period of twenty-four

(24) months following the date of termination, pay the full premium cost of the Executive’s participation in the Company’s group medical and dental insurance plans, provided that the Executive is entitled to continue such participation under applicable law and plan terms. In addition, any (I) outstanding unvested stock options granted or issued to the Executive as of the date of the Change in Control shall become vested and shall be exercisable for ninety (90) days following termination of the Executive’s employment and (II) shares of unvested restricted stock of the Company granted or issued to the Executive as of the date of the Change in Control shall become vested and no longer subject to forfeiture. The Company will also provide the Executive with an outplacement assistance benefit in the form of a lump-sum payment of $15,000 plus an additional lump-sum payment in an amount sufficient, after giving effect to all federal, state and other taxes with respect to such additional payment, to make Executive whole for all taxes (including withholding taxes) on such outplacement assistance benefit. For the purpose of this Section 5.g alone, in addition to the definition provided in Section 5.e, Good Reason shall also mean the relocation of the Executive’s principal office, without his prior consent, to a location more than thirty (30) miles from its location on the day prior to the Change in Control.

(a) Payment(s) by the Company and contributions to the cost of the Executive’s continued participation in the Company’s group health and dental plans that may be due the Executive in each case under the applicable termination provision of Section 5 shall constitute the entire obligation of the Company to the Executive. In order to receive any payments, benefits continuation, accelerated vesting of stock options or shares of restricted stock or any other benefits under Section 5.d or 5.e or 5.g or 5.h, the Executive must first execute a General Release of Claims in a form acceptable to the Company.

[SIGNATURE PAGE FOLLOWS]

2

Confidential

IN WITNESS WHEREOF, the parties each have caused this Amendment 1 to be executed by their respective duly authorized representative as of the date first set forth above.

3