A Study of STRO-002, an Anti-Folate Receptor Alpha Antibody Drug Conjugate, in Combination With Bevacizumab in Epithelial Ovarian Cancer

• ClinicalTrials.gov Identifier: NCT05200364
• Recruitment Status: Recruiting
• First Posted: January 20, 2022
• Last Update Posted: August 2, 2022
• Sponsor: Sutro Biopharma, Inc.
• Information provided by (Responsible Party): Sutro Biopharma, Inc.

Study Description

Brief Summary:

Phase 1 trial to study the safety, pharmacokinetic and Preliminary Efficacy of STRO-002 in combination with Bevacizumab.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer; Ovarian Carcinoma; Ovary Cancer; Fallopian Tube Cancer; Primary Peritoneal Carcinoma	Drug: STRO-002; Drug: Bevacizumab	Phase 1

Detailed Description:

This study is a Phase 1, open-label, multicenter, dose escalation study to assess preliminary efficacy for STRO-002 combined with bevacizumab in patients with advanced ovarian cancer that is refractory or has relapsed after standard available therapy. Fallopian tube and primary peritoneal cancers are treated in the same manner as epithelial ovarian cancers and are thus included in this study.

The dosing regimen will include bevacizumab administered at the labeled dose of 15 mg/kg IV q 3 weeks given together with STRO-002 at increasing dose levels administered IV q 3 weeks. The RP2D of STRO-002 given with bevacizumab 15 mg/kg q 3 weeks will be determined by dose escalation.

Dose expansion will enroll approximately 40 subjects with advanced relapsed ovarian cancer treated with STRO-002 plus bevacizumab at the RP2D determined in dose escalation. Subjects in the dose expansion portion of the study will be required at screening to submit both archival tumor tissue (if available and available tissue has adequate tumor) and tumor tissue from a biopsy done during screening to the central laboratory for analysis of FOLRα expression, both prior to enrollment in the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 58 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention Model Description: The study is designed as a 3+3 dose escalation/de-escalation of STRO-002 given in combination with the labeled dose of bevacizumab. The patient population is relapsed ovarian cancer and the study treatment is the combination of STRO-002 plus bevacizumab. This study will be conducted in 2 parts, dose escalation and dose expansion.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of STRO-002, an Anti-Folate Receptor Alpha Antibody Drug Conjugate, in Combination With Bevacizumab in Patients With Advanced Epithelial Ovarian Cancer (Including Fallopian Tube or Primary Peritoneal Cancers)
• Actual Study Start Date: March 22, 2022
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: January 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Experimental :STRO-002 treatment in combination with Bevacizumab; Dose Escalation: STRO-002 at increasing dose levels plus bevacizumab at 15 mg/kg Dose Expansion: STRO-002 at RP2D plus bevacizumab at 15 mg/kg	Drug: STRO-002; intravenous antibody drug conjugate; Drug: Bevacizumab; anti-VEGF agent; Other Name: Avastin

Outcome Measures

Primary Outcome Measures :

1. Part 1 - Safety and tolerability of STRO-002/bevacizumab as a combination therapy [ Time Frame: From baseline through end of study (approximately 24 months) ]
   Incidence and severity of adverse events (AEs) and clinical laboratory abnormalities observed across STRO-002/bevacizumab dose levels. Incidence of dose-limiting toxicities (DLTs) through Day 1-21 following administration of each initial STRO-002/bevacizumab dose.
2. Part 1 - Determine the recommended phase 2 dose (RP2D) of STRO-002/bevacizumab [ Time Frame: From baseline through end of study (approximately 24 months) ]
   Frequency of DLTs across STRO-002 dose levels

Secondary Outcome Measures :

1. Part 1 - Characterize the pharmacokinetics (PK) of STRO-002 by measuring the maximum plasma concentration (Cmax). [ Time Frame: From baseline through end of study (approximately 24 months) ]
   Measurement of maximum plasma concentration (Cmax) after the administration of STRO-002
2. Part 1 - Characterize the PK of STRO-002 by measuring the area under the plasma concentration versus time curve (AUC) [ Time Frame: From baseline through end of study (approximately 24 months) ]
   Measurement of AUC
3. Part 1 - Assess the formation of anti-drug antibodies (ADAs) to STRO-002 when administered with bevacizumab. [ Time Frame: From baseline through end of study (approximately 24 months) ]
   Circulating ADAs formed to STRO-002

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Patients are required to have ovarian, fallopian, or primary peritoneal cancer.
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥ 18 years.
2. ECOG 0-1
3. Life expectancy > 3 months
4. High Grade serous epithelial ovarian cancer (EOC), fallopian tube or primary peritoneal cancer with pathology report documentation of tumor type.
5. At least one measurable target lesion per RECIST v1.1.

6. Tumor tissue for FolRα expression testing prior to enrollment.

   1. For dose escalation: tissue may be from either archival tumor tissue or from a biopsy performed during screening.
   2. For dose expansion part of the study, tissue from both archival tumor tissue and a biopsy performed during screening is required.

7. Adequate bone marrow function defined as:

   1. Absolute neutrophil count (ANC) ≥1500/μL
   2. Hemoglobin ≥ 9g/dL
   3. Platelet count ≥ 100 x 10^3/μL

8. Adequate liver function defined as:

   1. ALT and AST < 2.5 x ULN
   2. ALP < 2.5 x ULN
   3. Bilirubin < 1.5 x ULN

9. Adequate renal function defined as serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) > 40 mL/min.

   Subjects enrolling into Dose Escalation must also meet the following inclusion criteria:

10. Relapsed and/or PD on last treatment regimen and one of the following:

    1. Primary Platinum refractory and received no more than 1 prior regimen
    2. Primary platinum resistant and received no more than 4 prior regimens

    3. Platinum sensitive and all of the following:

       • received at least 2 platinum-based therapies or received 1 platinum and 1 non-platinum based therapy (if unable to receive a second platinum regimen due to toxicity) or received at least 1 platinum-based therapy (if the regimen contained a PARP inhibitor given as maintenance treatment)
       • received no more than 1 additional regimen after becoming platinum resistant
       • received no more than 4 prior regimens

    Subjects enrolling into Part 2, Dose Expansion must also meet the following inclusion criteria:

11. Relapsed and/or PD on last treatment regimen and one of the following:

    1. Platinum resistant and received no more than 4 prior regimens

    2. Platinum sensitive and

       • received at least 2 platinum-based therapies or received 1 platinum and 1 non-platinum based therapy (if unable to receive a second platinum regimen due to toxicity) or received at least 1 platinum-based therapy (if the regimen contained a PARP inhibitor given as maintenance treatment)
       • received no more than 1 additional regimen after becoming platinum resistant
       • received no more than 4 prior regimens

Exclusion Criteria:

1. Low grade ovarian carcinoma (Grade 1).
2. Clear cell, mucinous, endometrioid, sarcomatous, and mixed histology ovarian carcinomas, endometrial leiomyosarcoma, and endometrial stromal sarcomas.
3. Prior treatment with an ADC with a tubulin inhibitor warhead.
4. Prior treatment with other FolRα targeting agents unless approved by a Sutro medical monitor or designee.
5. Subjects who are primary platinum-refractory during frontline treatment are excluded from the Expansion Cohort (Allowed in Dose Escalation if no more than 1 prior regimen).
6. Greater than 4 prior lines of treatment (> 1 prior if primary platinum refractory).
7. Any prior toxicity that required permanent discontinuation of bevacizumab or other contraindication to receive bevacizumab per institutional guidelines.
8. Previous solid organ transplantation.
9. Current signs/symptoms of bowel obstruction and/or signs/symptoms of or bowel obstruction within 3 months of initiation of study treatment.
10. Grade ≥2 toxicity from prior anticancer therapy with the exception of Grade 2 alopecia or Grade 2 neuropathy.
11. Uncontrolled hypertension
12. Sensory or motor neuropathy Grade > 1 at screening prior to initiation of study treatment.
13. Potentially fatal concurrent or recent malignancy. Subjects with past or current malignancy need to be discussed with the sponsor to determine eligibility.
14. Chronic or ongoing active infection requiring systemic treatment.
15. Ongoing immunosuppressive therapy, including systemic corticosteroids. Note: Physiologic replacement and use of topical or inhaled corticosteroids are allowed. Dexamethasone may be used to treat chemotherapy induced nausea per institutional guidelines.
16. Clinically significant cardiac disease.
17. History or clinical signs of meningeal or active central nervous system involvement.
18. Known severe COPD or asthma
19. Active pneumonitis within 6 months of initiating study treatment.
20. History of stroke or history of significant cerebrovascular disease (i.e., transient ischemic attack) within 6 months of initiation of study treatment.
21. History of pulmonary embolism or any Grade 3 thromboembolic event within 6 months of initiation of study treatment.
22. Known human immunodeficiency virus seropositivity.

23. Active hepatitis B or hepatitis C and positive serology (unless due to vaccination or passive immunization due to immunoglobulin therapy) with the following exceptions:

    1. Subject has had HCV but received antiviral treatment and shows no detectible HCV viral DNA for 6 months prior to screening
    2. Subject has had HBV but is HBV surface antigen (HBsAg) and viral DNA negative at screening
    3. Subject has had HBV but received antiviral treatment and have undetectable viral DNA for 6 months prior to screening
24. Concurrent participation in another therapeutic treatment trial
25. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
26. Females who are pregnant or breastfeeding, and all women of childbearing potential unwilling to use adequate barrier contraception while on treatment and for 16 weeks after last dose of STRO-002/bevacizumab and 6 months after the last dose of bevacizumab.

Contacts and Locations

Contacts

Contact: Craig Berman, MD; 650-801-6417; STRO-002ClinDev@sutrobio.com

Contact: Jason Kuriakose, MBA; 650-676-4642; STRO-002ClinDev@sutrobio.com

Locations

United States, Florida

University of South Florida,; Recruiting

Tampa, Florida, United States, 33612

Contact: Marlene Martin 813-844-5012 marlenecmartin@tgh.org

Principal Investigator: Matthew Anderson, MD

United States, Pennsylvania

Thomas Jefferson University; Recruiting

Philadelphia, Pennsylvania, United States, 19017

Contact 215-586-0199 askphase1@jefferson.edu

Principal Investigator: Russell Schilder, MD

University of Pennsylvania; Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contact: Christine Yang 215-349-8930 christine.yang@pennmedicine.upenn.edu

Principal Investigator: Lanie Martin, MD

United States, Tennessee

Tennessee Oncology; Recruiting

Nashville, Tennessee, United States, 37203

Contact 615-320-5090 DDUreferrals@sarahcannon.com

Principal Investigator: Erika Hamilton, MD

United States, Virginia

Virginia Cancer Specialists; Recruiting

Fairfax, Virginia, United States, 22031

Contact: Alexander Spira, MD 703-280-5390 alexander.spira@usoncology.com

Contact: Carrie Friedman (703) 280-5390 carrie.friedman@usoncology.com

United States, Wisconsin

Medical College of Wisconsin; Recruiting

Milwaukee, Wisconsin, United States, 53226

Contact: Matthew Lasowski 414-805-8594 mlasowski@mcw.edu

Principal Investigator: Denise Uyar, MD

Sponsors and Collaborators

Sutro Biopharma, Inc.

Investigators

• Study Chair: Arturo Molina, MD; Sutro Biopharma

More Information

• Responsible Party: Sutro Biopharma, Inc.
• ClinicalTrials.gov Identifier: NCT05200364
• Other Study ID Numbers: STRO-002-GM2
• First Posted: January 20, 2022
• Last Update Posted: August 2, 2022
• Last Verified: August 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Carcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Fallopian Tube Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases; Bevacizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors