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 Sidley Austin LLP

 1001 Page Mill Road

Building 1

 Palo Alto, CA 94304

(650) 565 7000

 (650) 565 7100 FAX

 BEIJING

 BOSTON

BRUSSELS

 CENTURY CITY

CHICAGO

 DALLAS

GENEVA

FOUNDED 1866

 HONG KONG

 HOUSTON

LONDON

 LOS ANGELES

NEW YORK

 PALO ALTO

SAN FRANCISCO

 SHANGHAI

 SINGAPORE

SYDNEY

 TOKYO

WASHINGTON, D.C.

 September 18, 2015

Securities and Exchange Commission

 Division of Corporation
Finance

 100 F Street, N.E.

 Washington, DC 20549

Attn: Ruairi Regan/Pamela Howell

Re:
CytomX Therapeutics, Inc.

Draft Pages from Amendment No. 3 to the

Registration Statement on Form S-1 (File No. 333-206658)

CIK No. 0001501989

 Ladies and Gentlemen:

Attached hereto please find draft marked pages from Amendment No. 3 to the Registration Statement on Form
S-1 (File No. 333-206658) (the “Registration Statement”) of CytomX Therapeutics, Inc. (the “Company”). The attached pages reflect (i) certain revisions to the
Registration Statement responsive to comments raised by the Staff of the Division of Corporation Finance of the Securities and Exchange Commission in regard to the Registration Statement in the Staff’s letter dated September 17, 2015 and
(ii) certain other revisions, including the share numbers and price range, reverse stock split and related disclosures throughout the filing, including the presentation of Use of Proceeds, Capitalization, Dilution and pro forma and other
financial information.

 Please contact me with any comments or questions regarding the attached. The Company would like to begin marketing
the offering on Monday, September 21, 2015, subject of course to the timing of the completion of the Staff’s review. I can be reached at (650) 565-7111. Thank you again for your consideration in this matter.

Very truly yours,

/s/ Sam Zucker

Sam Zucker

 Enclosures

cc:
Robert A. Ryan, Esq., Sidley Austin LLP
Mark V. Roeder, Esq., Latham & Watkins LLP
Brian J. Cuneo, Esq., Latham & Watkins LLP

 Sidley Austin (CA)
LLP is a Delaware limited liability partnership doing business as Sidley Austin LLP and practicing in affiliation with other Sidley Austin partnerships.

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  As filed with the Securities and Exchange Commission on September 21, 2015

Registration Number 333-206658

UNITED STATES

 SECURITIES
AND EXCHANGE COMMISSION

 WASHINGTON, D.C. 20549

  Amendment
No. 3

  to

FORM S-1

 REGISTRATION
STATEMENT

 UNDER

THE SECURITIES ACT OF 1933

 CYTOMX
THERAPEUTICS, INC.

 (Exact name of registrant as specified in its charter)

Delaware

2834

27-3521219

(State or other jurisdiction of incorporation or organization)

(Primary Standard Industrial Classification Code Number)

(I.R.S. Employer Identification Number)

343 Oyster Point Blvd.

Suite 100

 South San
Francisco, CA 94080

 (650) 515-3185

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Sean A. McCarthy, D.Phil.

President and Chief Executive Officer

CytomX Therapeutics, Inc.

343 Oyster Point Blvd.

Suite 100

 South San
Francisco, CA 94080

 (650) 515-3185

(Name, address, including zip code, and telephone number, including area code, of agent for service)

With copies to:

 Sam Zucker, Esq.

Robert A. Ryan, Esq.

 Sidley
Austin LLP

 1001 Page Mill Road, Building 1

Palo Alto, CA 94304

Telephone: (650) 565-7000

Fax: (650) 565-7100

 Mark V. Roeder, Esq.

Brian J. Cuneo, Esq.

 Latham
& Watkins LLP

 140 Scott Drive

Menlo Park, CA 94025

Telephone: (650) 328-4600

Fax: (650) 463-2600

 Approximate date of commencement of proposed sale to the public: As soon as practicable after this Registration
Statement becomes effective.

 If any of the securities being registered on this Form are to be offered on a delayed or continuous basis
pursuant to Rule 415 under the Securities Act of 1933 check the following box.  ¨

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the
following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ¨

If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the
Securities Act registration statement number of the earlier effective registration statement for the same offering.  ¨

If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the
Securities Act registration statement number of the earlier effective registration statement for the same offering.  ¨

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller
reporting company. See the definitions of “large accelerated filer,” “accelerated filer” and “smaller reporting company” in Rule 12b-2 of the Exchange Act. (Check one):

Large accelerated filer ¨

Accelerated filer ¨

Non-accelerated filer (Do not check if a smaller reporting company) x

Smaller reporting company ¨

CALCULATION OF REGISTRATION FEE

 Title of each class of

securities to be registered

 Amount

to be

 Registered(1)(2)

 Proposed

Maximum

 Aggregate
Offering

 Price Per Share(2)

 Proposed

Maximum

 Aggregate

Offering Price(1)(2)

 Amount of

Registration Fee(3)

 Common Stock, par value $0.00001 per share

7,187,500

$17.00

$122,187,500.00

$14,198.19

(1)
Includes 937,500 shares of common stock that the underwriters have the option to purchase.

(2)
Estimated solely for the purpose of calculating the amount of the registration fee in accordance with Rule 457(a) under the Securities Act of 1933, as amended.

(3)
The registrant previously paid a total of $11,620.00 in connection with previous filings of the registration statement. In accordance with Rule 457(a), an additional registration fee of $2,578.19 is being paid with this
amendment to the registration statement.

 The Registrant
hereby amends this Registration Statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment which specifically states that this Registration Statement shall thereafter
become effective in accordance with Section 8(a) of the Securities Act of 1933 or until the Registration Statement shall become effective on such date as the Commission, acting pursuant to said Section 8(a), may determine.

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 The information contained in this preliminary prospectus is not complete and may be
changed. We may not sell these securities until the registration statement filed with the Securities and Exchange Commission is effective. This preliminary prospectus is not an offer to sell these securities and is not soliciting an offer to buy
these securities in any jurisdiction where the offer or sale is not permitted.

Subject to Completion

Preliminary Prospectus dated September 21, 2015

PROSPECTUS

  6,250,000 Shares

 CytomX Therapeutics, Inc.

Common Stock

  We are
offering shares of our common stock. This is our initial public offering and no public market currently exists for our common stock. We expect the initial public offering price to be between $15.00 and $17.00 per share.

We have applied to list our common stock on The NASDAQ Global Market under the symbol “CTMX.” We are an “emerging growth
company” as defined by the Jumpstart Our Business Startups Act of 2012 and, as such, we have elected to comply with certain reduced public company reporting requirements for this prospectus and future filings.

Investing in our common stock involves a high degree of risk. Please read
“Risk Factors” beginning on page 13 of this prospectus before making a decision to invest in our common stock.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or
determined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

 PER SHARE

 TOTAL

 Public Offering Price

$

$

 Underwriting Discounts and Commissions*

$

$

 Proceeds to us before expenses

$

$

*
We refer you to “Underwriting” beginning on page 157 for additional information regarding underwriting compensation.

Pfizer Inc. (“Pfizer”), an existing stockholder and collaboration partner that is affiliated with one of our directors, has
indicated an interest in purchasing up to $5.0 million in shares of our common stock in this offering. In addition, Bristol-Myers Squibb Company (“BMS”), another of our collaboration partners, has indicated an interest in purchasing
up to $10.0 million in shares of our common stock in this offering. In each case, any shares of our common stock purchased by Pfizer or BMS would be purchased at the initial public offering price and on the same terms as the other purchasers in
this offering. However, because indications of interest are not binding agreements or commitments to purchase, each of Pfizer and BMS may purchase fewer shares than it indicated an interest in purchasing or not purchase any shares in this offering.

 Delivery of the shares of our common stock is expected to be made on or about
                    , 2015. We have granted the underwriters an option for a period of 30 days to purchase an additional 937,500 shares of our
common stock. If the underwriters exercise the option in full, the total underwriting discounts and commissions payable by us will be $                , and the total
proceeds to us, before expenses, will be $            .

 Joint
Book-Running Managers

BofA Merrill Lynch

Jefferies

Cowen and Company

 Co-Manager

Oppenheimer & Co.

 The date of this
prospectus is                     , 2015.

Table of Contents

 TABLE OF CONTENTS

 Explanatory Note

i

 About This Prospectus

ii

 Prospectus Summary

1

 The Offering

8

 Summary Financial and Other Data

10

 Risk Factors

12

 Special Note Regarding Forward-Looking Statements

50

 Statistical Data and Market Information

52

 Use of Proceeds

53

 Dividend Policy

55

 Capitalization

56

 Dilution

58

 Selected Historical Financial Information and Other Data

61

 Management’s Discussion and Analysis of Financial Condition and Results of Operations

63

 Business

77

 Management

121

 Executive and Director Compensation

131

 Certain Relationships and Related Party Transactions

141

 Principal Stockholders

145

 Description of Capital Stock

149

 Shares Eligible for Future Sale

154

 Material U.S. Federal Tax Consequences for Non-U.S. Holders of Common Stock

157

 Underwriting

160

 Legal Matters

167

 Experts

167

 Where You Can Find Additional Information

167

Explanatory Note

Unless we state otherwise or the context otherwise requires, references in this prospectus to:

•

“we,” “our,” “us,” “our company” and “CytomX” refer to CytomX Therapeutics, Inc.;

•

the “FDA” refer to the U.S. Food and Drug Administration;

•

“preferred stock” refer to our redeemable convertible preferred stock and convertible preferred stock;

•

the “JOBS Act” refer to the Jumpstart Our Business Startups Act of 2012;

•

the “Securities Act” refer to the Securities Act of 1933, as amended;

•

the “Exchange Act” refer to the Securities Exchange Act of 1934, as amended; and

•

the “SEC” refer to the Securities and Exchange Commission.

 i

Table of Contents

 PROSPECTUS SUMMARY

This summary highlights selected information contained in greater detail elsewhere in this prospectus and does not contain all of the
information you should consider before investing in our common stock. You should read this entire prospectus carefully, including our financial statements and the related notes included elsewhere in this prospectus. You should also consider, among
other things, the matters described under “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” in each case, appearing elsewhere in this
prospectus.

 Our Company

 Overview

  We are an oncology-focused biopharmaceutical company pioneering a novel class of antibody therapeutics based on our Probody
technology platform. We are using our platform to create proprietary cancer immunotherapies against clinically-validated targets as well as to develop first-in-class cancer therapeutics against novel targets. We believe that our Probody platform
will allow us to improve the combined efficacy and safety profile, or therapeutic window, of monoclonal antibody modalities including cancer immunotherapies, antibody drug conjugates (“ADCs”) and T-cell-recruiting bispecific antibodies.
Our Probody therapeutics are designed to take advantage of unique conditions in the tumor microenvironment to enhance the tumor-targeting features of an antibody and reduce drug activity in healthy tissues. We are currently developing Probody
therapeutics that address clinically-validated cancer targets in immuno-oncology, such as PD-L1, as well as novel targets, such as CD-166, that are difficult to drug and lead to concerns about damage to healthy tissues, or toxicities. In addition to
our proprietary programs, we are collaborating with strategic partners including BMS, Pfizer and ImmunoGen, Inc. (“ImmunoGen”) to develop selected Probody therapeutics. Our broad technology platform and lead product candidates are
supported by a decade of thorough scientific research and strong intellectual property, and we are advancing these candidates toward clinical trials. Our vision is to transform lives with safer, more effective therapies. To realize this vision we
are executing on our mission of changing the treatment of cancer by urgently advancing our Probody pipeline.

  The premise of our
Probody platform is to apply the prodrug concept to create a therapeutic antibody that remains inactive until it reaches the tumor. Probody therapeutics therefore have the potential to produce additional tumor specificity and enhanced safety
profiles because they are designed to have limited interaction with their molecular targets in healthy tissue. This approach of dosing drugs in a form such that they are only activated after reaching certain tissues is called the prodrug approach,
and has been used with many small molecule drugs, but has never before been effectively pursued using therapeutic antibodies.

 Cancer is
the second leading cause of death in the United States, accounting for nearly one in every four deaths. Over the past several decades, cancer research and treatment has evolved from small molecule chemotherapy agents to more targeted monoclonal
antibodies and, more recently, cancer immunotherapies that aim to enhance the ability of the immune system to attack tumors. Despite these advancements, many therapeutic antibodies have the inherent limitation of suboptimal therapeutic window. We
believe that there remains a significant need for therapeutics that are efficacious, safe and tolerable and that our technology represents the next evolution of targeted cancer therapies.

Our Platform

 A Probody
therapeutic consists of three components produced as a single protein by standard antibody production methodology: an active anti-cancer antibody, a mask for the antibody and a protease-cleavable linker. The mask is a peptide designed to disguise
the active binding site of the antibody to prevent the therapeutic from

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Table of Contents

 THE OFFERING

 Issuer

CytomX Therapeutics, Inc.

 Common stock offered by us

6,250,000 shares.

 Common stock to be outstanding immediately after this offering

34,509,170 shares (35,446,670 shares if the underwriters exercise in full their option to purchase additional shares of common stock).

 Underwriters’ option to purchase additional shares

We have granted the underwriters a 30-day option to purchase up to 937,500 additional shares at the public offering price less estimated underwritin