UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 13G

UNDER THE SECURITIES EXCHANGE ACT OF 1934

(Amendment No. 5)

Lixte Biotechnology Holdings, Inc.

(Name of Issuer)

Common Stock, $0.0001 par value per share

(Title of Class of Securities)

539319 10 3

(CUSIP Number)

January 11, 2017

(Date of Event Which Requires Filing of this Statement)

Check the appropriate box to designate the rule pursuant to which this Schedule is filed:

[  ]   Rule 13d-1(b)

[X]  Rule 13d-1(c)

[  ]   Rule 13d-1(d)

*The remainder of this cover page shall be filled out for a reporting person’s initial filing on this form with respect to the subject class of securities, and for any subsequent amendment containing information which would alter the disclosures provided in a prior cover page.

The information required in the remainder of this cover page shall not be deemed to be “filed” for the purpose of Section 18 of the Securities Exchange Act of 1934 (“Act”) or otherwise subject to the liabilities of that section of the Act but shall not be subject to all other provisions of the Act (however, see the Notes).

¹ Includes (1) 3,299,539 shares of common stock, and (2) options to purchase up to 2,500,000 shares of common stock pursuant to consulting agreements, as amended, between Mr. Schwartzberg and the Issuer.

² Includes (1) 2,334,000 shares of common stock and (2) options to purchase up to 1,000,000 shares of common stock.

³ Based on 51,375,814 shares of common stock outstanding comprised of 47,875,814 shares outstanding as of November 1, 2016, as reflected in the Issuer’s Form 10-Q for the quarter ended September 30, 2016, and 3,500,000 shares subject to options.

⁽¹⁾ Includes (1) 2,504,245 shares of common stock and (2) options/warrants to purchase up to 1,000,000 shares of common stock.

⁽²⁾ Includes (1) 2,334,000 shares of common stock and (2) options to purchase up to 1,000,000 shares of common stock.

⁽³⁾ Based on 49,875,814 shares of common stock outstanding comprised of 47,875,814 shares outstanding as of November 1, 2016, as reflected in the Issuer’s Form 10-Q for the quarter ended September 30, 2016, and 2,000,000 shares subject to warrants/options.

The name of the issuer is Lixte Biotechnology Holdings, Inc. (the “Issuer”).

The address of the Issuer’s principal executive office is 248 Route 25A, No. 2, East Setauket, New York 11733.

The names of the individuals are Gil N. Schwartzberg and Debbie Schwartzberg (each a “Reporting Person” and, collectively, the “Reporting Persons”). The Reporting Persons are husband and wife and hold the shares reported in Rows 5 & 7 of their respective cover pages as separate property.

The address of Gil N. Schwarzberg is 5500 Military Trail, Suite 22, Box 356, Jupiter, Florida 33458.

The address of Debbie Schwarzberg is 5500 Military Trail, Suite 22, Box 356, Jupiter, Florida 33458.

Gil N. Schwartzberg is a United States citizen.

Debbie Schwartzberg is a United States citizen.

The title of the class of securities to which this statement relates is the common stock of the Issuer, $0.0001 par value per share (the “Common Stock”).

The CUSIP number is 539319103.

The information required by Items 4(a) – (c) is set forth in Rows 5 – 11 of the cover pages and is incorporated herein by reference.

As of December 21, 2016, Gil N. Schwartzberg was the beneficial owner of 9,133,539 shares of common stock. Mr. Schwartzberg owns approximately 17.77% of the shares of Common Stock outstanding, based on 51,375,814 shares of common stock outstanding, which is the sum of the 47,875,814 shares reported to be outstanding on the Issuer’s Form 10-Q for the quarterly period ended September 30, 2016 and 3,500,000 shares subject to options. Mr. Schwartzberg has the sole power to vote, or to direct the vote of, and to dispose of, or to direct the disposition of, 5,799,539 shares.

As of December 21, 2016, Debbie Schwartzberg was the beneficial owner of 6,838,845 shares of common stock. Dr. Schwartzberg owns approximately 13.71% of the shares of Common Stock outstanding, based on 49,875,814 shares of Common Stock outstanding, which is the sum of the 47,875,814 shares reported to be outstanding on the Issuer’s Form 10-Q for the quarterly period ended September 30, 2016 and 2,000,000 shares subject to options. Dr. Schwartzberg has the sole power to vote, or to direct the vote of, and to dispose of, or to direct the disposition of, 3,504,845 shares.

The 3,334,000 shares reported in Rows 6 and 8 for each Reporting Person are held in two separate trusts, with respect to which Mr. Schwartzberg and Dr. Schwartzberg are co-trustees. The first trust holds 1,184,000 shares of common stock and options to purchase 500,000 shares. The second trust holds 1,150,000 shares of common stock and options to purchase 500,000 shares. Mr. Schwartzberg and Dr. Schwartzberg share the power to vote, or to direct the vote of, and to dispose of, or to direct the disposition of, the 3,334,000 shares held by the two trusts.

Each Reporting Person disclaims beneficial ownership, as such term is defined under Rule 13d-3, of the securities reported by the other Reporting Person in Rows 5 & 7 of the respective cover pages.

If this Schedule is being filed to report the fact that as of the date hereof the Reporting Person has ceased to be the beneficial owner of more than five percent of the class of securities, check the following [  ].

Not Applicable.

Not Applicable.

Not Applicable.

Not Applicable.

By signing below I certify that, to the best of my knowledge and belief, the securities referred to above were not acquired and are not held for the purpose of or with the effect of changing or influencing the control of the issuer of the securities and were not acquired and are not held in connection with or as a participant in any transaction having that purpose or effect.

SIGNATURE

After reasonable inquiry and to the best of my knowledge and belief, I certify that the information set forth in this statement is true, complete and correct.