Discovery of STRO-002, a Novel Homogeneous ADC Targeting Folate Receptor Alpha - for the Treatment of Ovarian and Endometrial Cancers

Sep 24, 2026

Uploaded by hdkawk

STRO-002 is a novel homogeneous folate receptor alpha (FolRa) targeting antibody-drug conjugate (ADC) evaluated in the clinic for ovarian and endometrial cancers. The study details STRO-002 discovery and optimization, including conjugation of a cleavable 3-aminophenyl hemiasterlin linker-warhead (SC239) to an anti-FolRa antibody, yielding a homogeneous ADC with DAR 4. STRO-002 binds with high affinity, rapidly internalizes, releases the tubulin-targeting payload SC209, shows limited non-specific toxicity, demonstrates bystander killing in coculture, and remains stable in circulation with a 6.4-day mouse half-life. In xenograft and patient-derived xenograft models, a single dose strongly inhibits tumors, and combination with carboplatin or Avastin enhances efficacy. Phase I dose escalation is ongoing for ovarian and endometrial cancer patients.

LanguageEnglish

CategoryHealthcare

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Pages13

Reading Time33 min

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Abstract

STRO-002 design and ADC characteristics

Preclinical efficacy and ongoing clinical study

Introduction

Burden and unmet need in ovarian and endometrial cancers

Folate receptor alpha as a therapeutic target

Antibody-drug conjugates and prior FolRa-targeting efforts

MCT FIRST DISCLOSURES Discovery of STRO-002, a Novel Homogeneous ADC Targeting Folate Receptor Alpha, for the Treatment of Ovarian and Endometrial Cancers Xiaofan Li1, Sihong Zhou1, Cristina L. Abrahams2, Stellanie Krimm3, Jennifer Smith1, Krishna Bajjuri1, Heather T. Stephenson4, Robert Henningsen1, Jeffrey Hanson1, Tyler H. Heibeck1, Daniel Calarese1, CuongTran1, Gang Yin1, Ryan L. Stafford5, Alice Y. Yam1, Toni Kline6, VenitaI. De Almeida7, Aaron K. Sato5, Mark LupherJr, Kristin Bedard1, and Trevor J. Hallam1 |
ABSTRACT | | | --- | --- | | STRO-002 is a novel homogeneous folate receptor alpha (FolRa) targeting antibody–drug conjugate (ADC) currently being investigatedin the clinic asa treatment for ovarian and endometrial cancers. Here, we describe the discovery, optimization, and antitumor properties of STRO-002. STRO-002 was generated by conjugation of a novel cleavable 3-aminophenyl hemiasterlin linker-warhead (SC239) to the nonnatural amino acid para-azidomethyl-L-phenylalanine incorporated at speciﬁc positions within a high afﬁnity anti-FolRa antibody using Sutro’s XpressCFþ, which resulted ina homogeneous ADC with a drug–antibody ratio (DAR) of 4. STRO-002 binds to FolRa with high afﬁnity, internalizes rapidly into target positive cells, and releases the tubulin-targeting cytotoxin 3-aminophenyl hemiasterlin (SC209). SC209 has reduced potential for drug efﬂux via P-glycoprotein 1 drug pump compared with other tubulin-targeting payloads. While STRO-002 lacks nonspeciﬁc cytotoxicity toward FolRa-negative cell lines, bystander killing of target negative cells was observed when cocultured with target positive cells. STRO-002 is stable in circulationwith no change in DAR for upto21days and has a half-life of 6.4 days in mice. A single dose of STRO-002 induced signiﬁcant tumor growth inhibition in FolRa-expressing xenograft models and patient-derived xenograft models. In addition, combination treatment with carboplatin or Avastin further increased STRO-002 efﬁcacy in xenograft models. The potent and speciﬁcpreclinical efﬁcacy of STRO-002 supports clinical development of STRO-002 for treating patients with FolRa-expressing cancers, including ovarian, endometrial, and non–small cell lung cancer. Phase I dose escalation for STRO-002 is in progress in ovarian cancer and endometrial cancer patients(NCT03748186andNCT05200364). | | | 1Sutro Biopharma, South San Francisco, California. 2Seagen, South San Francisco, California. 3Genentech, South San Francisco, California. 4Gilead, Foster City, California. 5Twist Bioscience, South San Francisco, California. 6Engine Biosciences, San Carlos, California. 73T Biosciences, South San Francisco, California.
Corresponding Author: Xiaofan Li, Sutro Biopharma, 111 Oyster Point Blvd, South San Francisco, CA 94080 . Phone: 650-801-6434; E-mail: [xli@sutrobio.com](xli@sutrobio.com)
Mol Cancer Ther 2023;22:155–67
doi: 10.1158/1535-7163 . MCT-22-0322
This open access article is distributed under the Creative Commons AttributionNonCommercial-NoDerivatives 4 . 0 International (CC BY-NC-ND 4 . 0) license.
􀀂2022The Authors;Published by the American Association for Cancer Research | Introduction
In the United States, gynecologic cancers account for more than 10% of all cancers in women and are known for their aggressive nature at advanced stages (1) . Ovarian cancers are often asymptomatic at early stages, resulting in late-stage diagnosis and poor prognosis with a 5-year survival rate of only 49.1%(2) . Endometrial cancer is the most common gynecologic cancer in the US and is the only gynecologic cancer that has increased both in incidence and mortality in recent years (3) . Despite the recent progress in targeted therapies and immunotherapies, surgical removal and chemotherapy remain the standard of care (SOC) for patients with ovarian and endometrial cancer (2, 4) and there persists to be an unmet medical need for treatments in metastatic, recurrent, and chemotherapyresist

FAQs

What is STRO-002 and what target does it recognize?

STRO-002 is a folate receptor alpha (FolRa) targeting antibody-drug conjugate (ADC). It binds to FolRa, internalizes into target-positive cells, and releases a tubulin-targeting cytotoxin payload.

How was STRO-002 constructed and what is its drug–antibody ratio?

STRO-002 was generated by conjugating a cleavable linker-warhead (SC239) to a nonnatural amino acid (para-azidomethyl-L-phenylalanine) incorporated at specific positions in a high-affinity anti-FolRa antibody. This produced a homogeneous ADC with a drug–antibody ratio (DAR) of 4.

What preclinical results support STRO-002’s clinical development?

STRO-002 shows high-affinity binding, rapid internalization, and stable circulation. It induces significant tumor growth inhibition in FolRa-expressing xenograft and patient-derived xenograft models, and combination therapy with carboplatin or Avastin further increases efficacy.

Sep 24, 2026

Uploaded by hdkawk