STRO-002 + Bevacizumab for Ovarian Cancer

No longer recruiting at 5 trial locations

Overseen By Jason Kuriakose, MBA

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Sutro Biopharma, Inc.

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Low grade ovarian carcinoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for women with high-grade serous ovarian cancer that has recurred or worsened after treatment. It combines two drugs, STRO-002 (an experimental treatment) and bevacizumab (also known as Avastin), to assess their safety and effectiveness together. The trial seeks women with this type of ovarian cancer who have undergone similar treatments before. Participants should not have certain other health issues, such as uncontrolled high blood pressure or recent serious infections. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, ongoing immunosuppressive therapy and certain conditions like uncontrolled hypertension or active infections may affect eligibility.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that STRO-002, when combined with bevacizumab, has promising safety results from earlier studies. One study found STRO-002 to be effective and safe for patients who had undergone many previous treatments. Among 33 patients evaluated, 24% showed a positive response, meaning their cancer responded well to the treatment.

STRO-002 has also been tested in lab settings, where it effectively slowed or stopped tumor growth. While these results are encouraging, they remain early findings.

Bevacizumab, the other drug in this trial, already has FDA approval for treating ovarian cancer. It has been shown to delay the worsening of cancer by more than six months in patients with advanced stages of the disease, indicating it is generally well-tolerated.

Overall, the combination of STRO-002 and bevacizumab has demonstrated a good safety profile so far, but more research is needed to fully understand its effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about STRO-002 combined with Bevacizumab for ovarian cancer because it introduces a novel approach to treating this condition. Unlike standard treatments that primarily target the cancer's growth pathways, STRO-002 is an antibody-drug conjugate designed to deliver a potent chemotherapy agent directly to cancer cells, potentially increasing effectiveness while reducing side effects. Bevacizumab, which is already used in treating ovarian cancer by inhibiting blood vessel growth to tumors, complements STRO-002 by enhancing its delivery and efficacy. This combination aims to provide a more targeted and potentially more effective treatment option for patients.

What evidence suggests that this trial's treatments could be effective for ovarian cancer?

Research has shown that using STRO-002 with bevacizumab may effectively treat ovarian cancer. Early studies demonstrated that this combination reduced tumor growth by 96% more than when each treatment was used alone. In this trial, participants will receive the combination of STRO-002 and bevacizumab. Additionally, STRO-002 alone has helped 32% of patients with advanced ovarian cancer. Bevacizumab, also known as Avastin, has already been proven to prolong the period before cancer worsens. These findings suggest that combining STRO-002 and bevacizumab could be a strong option for fighting ovarian cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Arturo Molina, MD

Principal Investigator

Sutro Biopharma

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high-grade serous ovarian, fallopian tube, or primary peritoneal cancer. They should have a life expectancy of more than 3 months and at least one measurable lesion. Participants need good kidney, bone marrow, and liver function but can't join if they've had certain treatments like FolRα targeting agents or are pregnant/breastfeeding without using barrier contraception.

Inclusion Criteria

For the part of the study where the dose is increased: specific rules about how your cancer has responded to previous treatments and how it has reacted to platinum-based chemotherapy.

You have at least one specific tumor that can be measured according to certain guidelines.

To increase the amount of the drug given, the doctors may use a small piece of tissue from a previous tumor or take a new biopsy during the screening process.

Exclusion Criteria

Prior treatment with other FolRα targeting agents unless approved by a Sutro medical monitor or designee

Significant concurrent, uncontrolled medical condition

You have a low grade (Grade 1) ovarian cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation

STRO-002 is administered at increasing dose levels with bevacizumab to determine the recommended phase 2 dose (RP2D)

Approximately 24 months

Every 3 weeks (in-person)

Dose Expansion

Approximately 40 subjects receive STRO-002 at RP2D with bevacizumab to assess safety and preliminary efficacy

Approximately 24 months

Every 3 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• STRO-002

Trial Overview The study tests STRO-002 combined with Bevacizumab in patients with epithelial ovarian cancer to evaluate safety and early effectiveness. It's a Phase 1 trial where participants' response to the treatment is monitored through various health parameters.

How Is the Trial Designed?

Group I: Experimental :STRO-002 treatment in combination with Bevacizumab Experimental Treatment 2 Interventions

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

Bevacizumab is already approved in European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Avastin for:

• Colorectal cancer
• Breast cancer
• Non-small cell lung cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in United States as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Glioblastoma
• Renal cell carcinoma
• Cervical cancer
• Ovarian cancer

Approved in Japan as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Approved in Canada as Avastin for:

• Colorectal cancer
• Non-small cell lung cancer
• Breast cancer
• Renal cell carcinoma
• Ovarian cancer

Who Is Running the Clinical Trial?

Sutro Biopharma, Inc.

Lead Sponsor

Trials

7

Recruited

1,100+

Published Research Related to This Trial

Bevacizumab, an anti-VEGF therapy, has shown efficacy in treating epithelial ovarian cancers, both as a standalone treatment and in combination with other therapies, based on evidence from Phase II trials involving various patient populations.

While most side effects of bevacizumab, such as proteinuria and hypertension, are mild and manageable, there are serious but rare risks like arterial thromboembolism and gastrointestinal perforation, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with bevacizumab in the management of epithelial ovarian cancer. Burger, RA.[2015]

In a study of 76 women with recurrent ovarian cancer, low-dose bevacizumab (7.5 mg/kg every 3 weeks) demonstrated effectiveness, with a median progression-free survival of 11.1 months and overall survival of 22.3 months.

The combination of bevacizumab with gemcitabine and carboplatin was particularly beneficial, especially for patients who were platinum-resistant, indicating its potential as a valuable treatment option in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose (7.5 mg/kg) bevacizumab may be a viable option in recurrent ovarian cancer: A retrospective study. Demirkiran, A., Eryilmaz, MK., Karaagac, M., et al.[2023]

Bevacizumab, an anti-VEGF monoclonal antibody, has been shown to be effective in treating recurrent high-grade serous ovarian cancer, leading to its regulatory approval in many countries, including the US in 2014.

While bevacizumab is widely used and integrated into ovarian cancer treatment guidelines, it does not increase cure rates, highlighting the need for predictive biomarkers to better tailor treatments and weigh the benefits against costs and potential toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-angiogenic agents in ovarian cancer: past, present, and future. Monk, BJ., Minion, LE., Coleman, RL.[2023]

Bevacizumab, an anti-VEGF monoclonal antibody, has shown significant efficacy in treating epithelial ovarian cancer (EOC) when added to chemotherapy, as demonstrated in four positive randomized trials involving both front-line and recurrent cases.

The ongoing debate in clinical practice is not whether to use bevacizumab, but rather when to use it, as considerations of efficacy, toxicity, quality of life, and cost-effectiveness play crucial roles in determining the optimal treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating bevacizumab into the management of epithelial ovarian cancer: the controversy of front-line versus recurrent disease. Monk, BJ., Pujade-Lauraine, E., Burger, RA.[2020]

In a study of 46 patients with advanced and recurrent epithelial ovarian cancer treated with bevacizumab and chemotherapy over 30 months, the most common adverse events were hypertension (65.2%) and proteinuria (49%), with hypertension typically occurring 2 months after treatment initiation.

Patients with a history of radiation therapy experienced a significantly higher risk of gastrointestinal perforation, indicating that careful consideration is needed when administering bevacizumab to these individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Associated With Long-term Treatment of Epithelial Ovarian Cancer With Bevacizumab and Chemotherapy. Yokoyama, Y., Kubo-Kaneda, M., Sunada, K., et al.[2022]

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor-A, has shown response rates of 16-21% as a single-agent treatment for recurrent ovarian cancer, indicating its efficacy in this context.

In combination with standard chemotherapy for advanced ovarian cancer, bevacizumab significantly improves progression-free survival, although it does not enhance overall survival; the main safety concern is hypertension, with rare but serious risks including gastrointestinal perforation and toxicity to the kidneys and central nervous system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and ovarian cancer. Garcia, A., Singh, H.[2021]

In a phase II clinical trial involving 62 women with advanced ovarian cancer, the combination of carboplatin, paclitaxel, and bevacizumab showed promising efficacy, with 75% of patients experiencing radiographic responses and a 36-month progression-free survival rate of 58%.

The treatment regimen was generally safe, with mild toxicity reported; however, there were instances of serious side effects, including two pulmonary embolisms and two gastrointestinal perforations, all occurring during the chemotherapy phase, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab as first-line chemotherapy for advanced mullerian tumors. Penson, RT., Dizon, DS., Cannistra, SA., et al.[2022]

Bevacizumab, a monoclonal antibody that targets VEGF, has shown anticancer activity in ovarian cancer, both as a single agent and in combination with chemotherapy, leading to its FDA approval for several cancers.

While bevacizumab can be effective, there is a significant risk of gastrointestinal perforation, especially in patients who have been heavily pretreated, which is an important consideration for patients and healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab and its use in epithelial ovarian cancer. Matulonis, UA.[2019]

Bevacizumab has been shown to be effective in managing epithelial ovarian cancer, particularly when combined with cytotoxic chemotherapy, as indicated by phase III trial data that demonstrate improved progression-free survival.

There is a compelling argument for using bevacizumab as a single agent in patients with platinum-resistant ovarian cancer, suggesting a more rational and potentially cost-effective approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of bevacizumab in the management of ovarian cancer: an argument for single-agent rather than combination therapy. Markman, M.[2020]

Bevacizumab, when combined with carboplatin and paclitaxel, significantly prolongs progression-free survival in women with newly diagnosed advanced ovarian cancer, as shown in the GOG-0218 and ICON7 studies.

In patients with recurrent platinum-sensitive ovarian cancer, bevacizumab combined with carboplatin and gemcitabine also extends progression-free survival, demonstrating its efficacy in both first-line and second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Dhillon, S.[2019]

Bevacizumab (BV) has been shown to significantly improve progression-free survival in patients with advanced ovarian cancer when combined with standard chemotherapy, although it does not extend overall survival.

While BV is associated with some adverse events like hypertension and bleeding, these can generally be managed effectively, and it also enhances the quality of life for patients with recurrent ovarian cancer, particularly regarding abdominal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab in ovarian cancer: A critical review of phase III studies. Rossi, L., Verrico, M., Zaccarelli, E., et al.[2022]

Bevacizumab, a targeted therapy for ovarian cancer, has shown significant improvement in progression-free survival when combined with standard chemotherapy, although it does not extend overall survival.

While bevacizumab can lead to adverse effects like hypertension and bleeding, these can generally be managed effectively, and the treatment has been approved in Europe and the U.S. for its benefits, including improved quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Critical appraisal of bevacizumab in the treatment of ovarian cancer. Yoshida, H., Yabuno, A., Fujiwara, K.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05200364

NCT05200364 | A Study of STRO-002, an Anti-Folate ... This study is a Phase 1, open-label, multicenter, dose escalation study to assess preliminary efficacy for STRO-002 combined with bevacizumab in patients ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT381480

STRO-002-GM2: A phase 1, open-label, safety, ... Pre-clinical models tested with STRO-002/bevacizumab combinations demonstrated additive anti-tumor activity compared to monotherapy. This study is a first in ...

3. sutrobio.com sutrobio.com/wp-content/uploads/2022/06/Sutro_ASCO2022_FINAL.pdf

STRO-002-GM2 (A) Co-administration of STRO-002 and bevacizumab (anti-VEGF), both administered once, significantly improved human tumor growth inhibition (96% ...

4. avastin.com avastin.com/hcp/ovar/efficacy-data.html

Avastin® (bevacizumab) Clinical Trials for Ovarian Cancer Ovarian Cancer: Avastin Efficacy Data · Patients achieved a median PFS benefit of >6 months in stage III or IV ovarian cancer after primary surgery · Select ...

5. onclive.com onclive.com/view/stro-002-produces-deep-responses-in-heavily-pretreated-advanced-ovarian-cancer

STRO-002 Produces Deep Responses in Heavily ... Earlier data from the trial showed that STRO-002 produced responses in 32% of 31 patients treated at clinically active dose levels of 2.9 mg/kg ...

6. onclive.com onclive.com/view/stro-002-shows-early-efficacy-safety-in-heavily-pretreated-epithelial-ovarian-cancer

STRO-002 Shows Early Efficacy, Safety in Heavily ... Results showed that the ADC elicited an overall response rate (ORR) of 24% in a total of 33 evaluable patients who had post-baseline scans ...