Biomarker-Driven Therapy for Ovarian Cancer

(BOUQUET Trial)

Recruiting at 83 trial locations

Overseen By Reference Study ID Number: WO42178 https://forpatients.roche.com/

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must not be taking: Chemotherapy, Radiotherapy, Immunotherapy, others

Disqualifiers: Pregnancy, CNS metastases, Severe infection, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

176 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will evaluate the efficacy and safety of multiple biomarker-selected treatments in patients with persistent or recurrent rare epithelial ovarian, fallopian tube, or primary peritoneal tumors. Enrollment will take place in two phases: a preliminary phase followed by a potential expansion phase.

Will I have to stop taking my current medications?

The trial requires that you stop taking chemotherapy, radiotherapy, antibody therapy, immunotherapy, gene therapy, vaccine therapy, or investigational therapy at least 28 days before starting the study treatment. Hormonal therapy must be stopped at least 14 days before starting the study treatment.

What data supports the effectiveness of the drug combination used in the Biomarker-Driven Therapy for Ovarian Cancer trial?

Research shows that adding bevacizumab (an anti-angiogenic agent) to chemotherapy has a positive effect in treating ovarian cancer, as demonstrated in two large phase III trials. Additionally, the use of atezolizumab (an immune checkpoint inhibitor) in combination with chemotherapy and bevacizumab is being evaluated for its potential benefits in newly diagnosed advanced ovarian cancer. ^{1 2 3 4 5}

What safety data exists for the treatment options in the Biomarker-Driven Therapy for Ovarian Cancer trial?

The IMagyn050 trial evaluated the safety of atezolizumab combined with chemotherapy and bevacizumab in newly diagnosed ovarian cancer, indicating it was generally safe for patients. The KEYNOTE-028 trial assessed pembrolizumab in advanced ovarian cancer, finding it to be safe and tolerable. Letrozole was also found to be safe in estrogen receptor-positive ovarian cancer patients. ^{1 6 7 8 9}

What makes the drug combination in the Biomarker-Driven Therapy for Ovarian Cancer trial unique?

This drug combination is unique because it uses a variety of targeted therapies, including PARP inhibitors, anti-angiogenic agents, and immune checkpoint inhibitors, to address the diverse molecular characteristics of ovarian cancer, potentially improving treatment effectiveness by tailoring therapy to individual patient biomarkers. ^{3 5 10 11 12}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for patients with rare epithelial ovarian tumors that have come back or didn't go away after treatment. They must have had 1-4 previous treatments including platinum-based therapy, be in good physical condition, and agree to use birth control. It's not for those who are pregnant, breastfeeding, or have certain other cancers or severe infections.

Inclusion Criteria

You have a disease that can be measured using a specific set of guidelines.

Agreement to remain abstinent or use contraception, and refrain from donating eggs for women of childbearing potential

My blood and organs are functioning well.

Exclusion Criteria

I have been diagnosed with endometrial cancer at the same time as another primary cancer.

My current diagnosis is a borderline ovarian tumor.

I have a specific type of advanced ovarian, fallopian tube, or peritoneal cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preliminary Phase

Participants receive biomarker-selected treatments to evaluate efficacy and safety

Until unacceptable toxicity or disease progression

Expansion Phase

Potential expansion of treatment based on preliminary phase results

Until unacceptable toxicity or disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

Treatment Details

Interventions

• Abemaciclib
• Atezolizumab
• Bevacizumab
• Cobimetinib
• Cyclophosphamide
• Giredestrant
• Inavolisib
• Ipatasertib
• Letrozole
• Luteinizing Hormone-Releasing Hormone (LHRH) Agonists
• Olaparib
• Paclitaxel
• Palbociclib
• Trastuzumab Emtansine

Trial Overview The study tests how well different drugs work based on tumor markers in patients with persistent/recurrent ovarian tumors. Drugs like Abemaciclib and Trastuzumab Emtansine among others will be used. The trial includes initial and potential expansion phases to assess safety and effectiveness.

Participant Groups

Group I: Trastuzumab Emtansine (ERBB2-amplified/mutant tumors) Experimental Treatment 1 Intervention

Participants in the Trastuzumab Emtansine arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group II: Ipatasertib + Paclitaxel (PIK3CA/AKT1/PTEN-altered tumors) Experimental Treatment 2 Interventions

Participants in the Ipatasertib + Paclitaxel arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group III: Inavolisib + Palbociclib + Letrozole (ER+ and PIK3CA-altered tumors) Experimental Treatment 4 Interventions

Participants in the Inavolisib + Palbociclib + Letrozole arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group IV: Inavolisib + Palbociclib (PIK3CA-altered tumors) Experimental Treatment 2 Interventions

Participants in the Inavolisib + Palbociclib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group V: Inavolisib + Olaparib (Non-matched) Experimental Treatment 2 Interventions

Participants in the Inavolisib + Olaparib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group VI: Inavolisib + Giredestrant (ER+ and PIK3CA-altered tumors) Experimental Treatment 2 Interventions

Participants in the Inavolisib + Giredestrant arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group VII: Inavolisib + Bevacizumab (PIK3CA-altered tumors) Experimental Treatment 2 Interventions

Participants in the Inavolisib + Bevacizumab arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group VIII: Giredestrant + Abemaciclib (ER+ tumors) Experimental Treatment 3 Interventions

Participants in the Giredestrant + Abemaciclib arm will receive treatment until unacceptable toxicity or disease progression as determined by the investigator according to RECIST v1.1.

Group IX: Cobimetinib (BRAF/NRAS/KRAS/NF1-altered tumors) Experimental Treatment 1 Intervention

Participants in the Cobimetinib arm will receive treatment until unacceptable toxicity or disease progression per RECIST v1.1.

Group X: Atezolizumab + Bevacizumab + Cyclophosphamide (Non-matched) Experimental Treatment 3 Interventions

Participants in the Atezolizumab + Bevacizumab + Cyclophosphamide arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.

Group XI: Atezolizumab + Bevacizumab (Non-matched) Experimental Treatment 2 Interventions

Participants in the Atezolizumab + Bevacizumab arm will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator after an integrated assessment of radiographic and biochemical data, local biopsy results (if available), and clinical status.

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Findings from Research

Despite high initial response rates to surgery and platinum-based chemotherapy in ovarian cancer, most patients experience relapse, highlighting the need for new treatment strategies to improve survival.

Recent phase III trials have shown that the anti-angiogenic agent bevacizumab, when used alongside chemotherapy and as maintenance therapy, can positively impact outcomes in first-line ovarian cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal first-line treatment in ovarian cancer. Raja, FA., Chopra, N., Ledermann, JA.[2022]

The PENELOPE trial found that adding pertuzumab to chemotherapy for patients with platinum-resistant ovarian cancer did not significantly improve overall survival, with a hazard ratio of 0.90, indicating no meaningful difference between the treatment and control groups.

While pertuzumab did not enhance patient-reported outcomes overall, it was associated with increased diarrhea symptoms, suggesting a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. Lorusso, D., Hilpert, F., González Martin, A., et al.[2022]

Adjuvant hormone therapy (AHT) significantly improves overall survival in women with epithelial ovarian cancer, with a hazard ratio of 0.63, indicating a 37% reduction in the risk of death compared to those not receiving AHT.

The study, which included 150 patients followed for a median of 19.1 years, also showed that AHT enhances relapse-free survival, suggesting that it not only helps manage menopausal symptoms but may also positively impact cancer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial. Eeles, RA., Morden, JP., Gore, M., et al.[2019]

Epithelial ovarian cancer (EOC) has a high initial response rate to platinum-based treatments (70-80%), but long-term survival remains low due to chemoresistance and the disease's heterogeneity, which includes multiple histological subtypes.

Recent advancements in biomarker research, such as identifying BRCA and KRAS mutations, have led to the development of targeted therapies like PARP inhibitors and immunotherapy, which may improve treatment outcomes for patients with EOC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring the Clinical Impact of Predictive Biomarkers in Serous Ovarian Carcinomas. Le Page, C., Chung, J., Rahimi, K., et al.[2021]

In the phase III IMagyn050 trial involving patients with newly diagnosed ovarian cancer, the addition of atezolizumab to standard chemotherapy did not improve progression-free survival (PFS) in patients with BRCA1/2 mutations or homologous recombination deficiency (HRD).

Despite the presence of BRCA1/2 mutations or HRD, most ovarian tumors exhibited low tumor mutation burden (TMB), indicating that genomic instability does not predict enhanced sensitivity to immune checkpoint inhibitors like atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. Landen, CN., Molinero, L., Hamidi, H., et al.[2023]

In a phase Ib trial involving 26 patients with advanced PD-L1-positive ovarian cancer, pembrolizumab demonstrated a confirmed objective response rate of 11.5%, indicating some level of antitumor activity, with 1 complete response and 2 partial responses observed.

The treatment was generally well-tolerated, with 73.1% of patients experiencing treatment-related adverse events, but no deaths or treatment discontinuations due to these events, suggesting that pembrolizumab has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. Varga, A., Piha-Paul, S., Ott, PA., et al.[2019]

In a phase II study of 42 ER-positive ovarian cancer patients treated with letrozole, 17% showed a significant response in CA125 levels, indicating some efficacy of the drug in this specific patient group.

The study identified predictive markers, such as low HER2 expression, that may help determine which patients are more likely to respond to letrozole treatment, highlighting the potential for personalized therapy in ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients. Smyth, JF., Gourley, C., Walker, G., et al.[2022]

The combination of aflibercept and docetaxel was found to be safe and well-tolerated in women with recurrent ovarian cancer, with no dose-limiting toxicities reported during the phase 1 study.

In the phase 2 trial involving 46 patients, the treatment achieved a confirmed objective response rate of 54%, indicating significant antitumor activity, which supports further clinical development of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1-2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. Coleman, RL., Duska, LR., Ramirez, PT., et al.[2021]

The standard treatment for platinum-resistant ovarian cancer involves non-platinum chemotherapy, with weekly paclitaxel showing the greatest benefits, but overall response rates remain modest, highlighting the need for improved therapies.

Recent trials indicate that while combination treatments with antiangiogenics have improved outcomes, there is still a lack of reliable biomarkers to predict treatment response, emphasizing the importance of thoughtful clinical trial designs and the exploration of novel therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. Eskander, RN., Moore, KN., Monk, BJ., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab, Bevacizumab, and Chemotherapy for Newly Diagnosed Stage III or IV Ovarian Cancer: Placebo-Controlled Randomized Phase III Trial (IMagyn050/GOG 3015/ENGOT-OV39). [2022]

2. England pubmed.ncbi.nlm.nih.gov

Optimal first-line treatment in ovarian cancer. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes and final overall survival results from the randomized phase 3 PENELOPE trial evaluating pertuzumab in low tumor human epidermal growth factor receptor 3 (HER3) mRNA-expressing platinum-resistant ovarian cancer. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Adjuvant Hormone Therapy May Improve Survival in Epithelial Ovarian Cancer: Results of the AHT Randomized Trial. [2019]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Exploring the Clinical Impact of Predictive Biomarkers in Serous Ovarian Carcinomas. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Influence of Genomic Landscape on Cancer Immunotherapy for Newly Diagnosed Ovarian Cancer: Biomarker Analyses from the IMagyn050 Randomized Clinical Trial. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab in patients with programmed death ligand 1-positive advanced ovarian cancer: Analysis of KEYNOTE-028. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Antiestrogen therapy is active in selected ovarian cancer cases: the use of letrozole in estrogen receptor-positive patients. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Phase 1-2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Biomarkers for systemic therapy in ovarian cancer. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Targeted trials in ovarian cancer. [2010]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Overcoming the challenges of drug development in platinum-resistant ovarian cancer. [2023]