Immunotherapy for Ovarian Cancer

(IPROC Trial)

Recruiting at 10 trial locations

Overseen By Janet Dancey

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Antivirals, Corticosteroids, Live vaccines

Disqualifiers: HIV, Hepatitis, Autoimmune, Cardiac, 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

Compensation: Varies

Number of Visits: 1

Duration: 8-12 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new drugs to evaluate their effectiveness against ovarian cancer that no longer responds to standard platinum-based treatments. Participants will receive different combinations of drugs, such as BA3011 (an experimental treatment), BA3021 (an experimental treatment), and Durvalumab (an immunotherapy drug), to assess their effects. Women with ovarian cancer that has progressed within six months after their last platinum-based chemotherapy and who have measurable disease might be suitable for this trial. The goal is to find more effective treatments for this challenging cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, a minimum of 4 weeks must have passed since your last dose of prior therapy before enrollment, and any reversible side effects from previous treatments should have improved to a mild level. It's best to discuss your specific medications with the trial team.

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

Previous studies have shown that the treatments BA3011 and BA3021, when combined with durvalumab, are generally safe. Durvalumab, already approved for some cancer types, is usually well-tolerated. Animal tests for BA3021 demonstrated safety even at high doses, indicating stability and safety. BA3011 has been tested in various cancers and has also shown a good safety record. Both BA3011 and BA3021 are targeted cancer therapies known as antibody-drug conjugates, which earlier trials have tested with positive results. Overall, these treatments have been found safe in earlier studies, though individual side effects may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for ovarian cancer because they represent innovative approaches that differ from traditional chemotherapy and targeted therapies. ENB-003 combined with Toripalimab is particularly intriguing due to its unique mechanism of enhancing the immune system's ability to recognize and attack cancer cells. This combination may offer a more precise and powerful response compared to standard treatments. Additionally, the use of Durvalumab, an immune checkpoint inhibitor, with BA3011 or BA3021, introduces novel antibodies that could potentially disrupt cancer cell defenses in new ways, offering hope for improved outcomes. These treatments could provide new options for patients with ovarian cancer, especially those who have not responded well to existing therapies.

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

Studies have shown that the drug combination of durvalumab and BA3021 can have promising effects on cancer. Early trials of BA3021 showed positive results in patients with advanced cancers, suggesting effectiveness against difficult-to-treat tumors like ovarian cancer. Durvalumab helps the immune system fight cancer cells, possibly enhancing BA3021's effects. Although this arm is closed, it provides valuable insights for ongoing research.

For the combination of durvalumab and BA3011, research indicates that BA3011 targets cancer cells in the tumor area, potentially making it a strong partner for durvalumab, which boosts the immune system. This arm is also closed, but the findings contribute to understanding potential treatment strategies.

Lastly, ENB-003 combined with toripalimab, an active arm in this trial, has shown encouraging results in early studies with other cancers, demonstrating disease control and some tumor shrinkage. This combination is thought to block pathways that cancer cells use to grow, giving the immune system a better chance to fight the cancer. ^{3 5 6 7 8}

Who Is on the Research Team?

Anna Tinker

Principal Investigator

BCCA - Vancouver Cancer Centre, BC Canada

Helen MacKay

Principal Investigator

Sunnybrook Health Sciences Centre, Toronto, Ontario Canada

Are You a Good Fit for This Trial?

This trial is for women with high grade serous ovarian cancer that's resistant to platinum-based chemotherapy. Participants must be over 18, have a life expectancy of at least 3 months, and an ECOG performance status of 0 or 1. They should not have uncontrolled illnesses or a history of severe autoimmune disorders in the past three years. Pregnant women and those who've had certain treatments recently are excluded.

Inclusion Criteria

My organ and bone marrow functions are currently healthy.

All patients must be registered for screening prior to study enrollment, however, if biomarker testing results are not required prior to enrollment to a substudy, then enrollment can proceed immediately.

Any side effects from my previous treatments have mostly gone away.

Exclusion Criteria

I have not received a live vaccine in the last 4 weeks.

My heart's electrical cycle is longer than normal, or I take medications that can extend this cycle.

My cancer has spread to my brain.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive experimental immunotherapy drugs to assess their effects on ovarian cancer

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BA3011
• BA3021
• Durvalumab
• To be determined

Trial Overview The study tests new drugs (BA3021, Durvalumab, BA3011) on ovarian cancer to see their effects. Patients will undergo pre-study screening for biomarkers which may determine their eligibility for specific substudies within the main trial.

How Is the Trial Designed?

Group I: ENB-003 + Toripalimab Experimental Treatment 2 Interventions

Group II: Durvalumab + BA3021 (Arm Closed) Experimental Treatment 2 Interventions

Group III: Durvalumab + BA3011 (Arm Closed) Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Cancer Research Institute, New York City

Collaborator

Trials

22

Recruited

1,300+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

BioAtla, Inc.

Industry Sponsor

Trials

7

Recruited

1,500+

Published Research Related to This Trial

The FDA has recently approved two antibody drug conjugates (ADCs) for gynecological cancers: tisotumab vedotin for recurrent cervical cancer and mirvetuximab soravtansine for platinum-resistant ovarian cancer, marking a significant advancement in treatment options.

Over 20 ADC formulations are currently in clinical trials for various gynecological tumors, highlighting the rapid expansion of this treatment class and the exploration of new targets and drug delivery methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating antibody drug conjugates in the management of gynecologic cancers. Chelariu-Raicu, A., Mahner, S., Moore, KN., et al.[2023]

The combination of mirvetuximab soravtansine and bevacizumab is well tolerated in patients with platinum-resistant ovarian cancer, with most adverse events being mild-to-moderate, including diarrhea and nausea.

This treatment showed a confirmed objective response rate of 39%, with particularly promising results (56% response rate) in patients who were less heavily pretreated and had higher levels of folate receptor alpha expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer. O'Malley, DM., Matulonis, UA., Birrer, MJ., et al.[2020]

In a phase III trial involving 156 patients with platinum-resistant ovarian carcinoma, adding pertuzumab to chemotherapy did not significantly improve progression-free survival (PFS) compared to placebo, with median PFS of 4.3 months for the pertuzumab group versus 2.6 months for the placebo group.

Subgroup analyses indicated that the addition of pertuzumab showed more promising trends in PFS specifically for patients receiving gemcitabine and paclitaxel, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-Blind, Placebo-Controlled, Randomized Phase III Trial Evaluating Pertuzumab Combined With Chemotherapy for Low Tumor Human Epidermal Growth Factor Receptor 3 mRNA-Expressing Platinum-Resistant Ovarian Cancer (PENELOPE). Kurzeder, C., Bover, I., Marmé, F., et al.[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]

Anti-mesothelin antibody-drug conjugates show promise as a novel treatment for ovarian cancer, with encouraging results from phase II trials indicating their efficacy and favorable safety profiles.

These therapies target mesothelin, which is commonly expressed in ovarian cancers, but further phase III trials are needed to confirm their effectiveness in treating recurrent and advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel mesothelin antibody-drug conjugates: current evidence and future role in the treatment of ovarian cancer. Mauricio, D., Harold, J., Tymon-Rosario, JR., et al.[2022]

The SGO Journal Club highlighted the recent FDA approval of two antibody-drug conjugates (ADCs) for treating cervical and ovarian cancer, showcasing their potential as new therapeutic options in gynecologic malignancies.

Discussions included the pharmacology and toxicities of ADCs, emphasizing the importance of understanding these factors in the context of clinical trials like GOG-3023 and the SORAYA study, which evaluated the efficacy and safety of Mirvetuximab Soravtansine in patients with platinum-resistant ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Society of Gynecologic Oncology Journal Club: Controversial conversations in Gynecologic cancer - The ABCs of ADCs (Antibody drug Conjugates). Martin, J., Zacholski, E., O'Cearbhaill, R., et al.[2023]

In a randomized phase II study involving 149 patients with platinum-sensitive recurrent advanced ovarian cancer, the addition of pertuzumab to carboplatin-based chemotherapy did not significantly improve progression-free survival (PFS) compared to chemotherapy alone.

Pertuzumab was well tolerated, showing no increase in cardiac adverse events, indicating it is a safe option to combine with chemotherapy despite not enhancing efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II study evaluating the combination of carboplatin-based chemotherapy with pertuzumab versus carboplatin-based therapy alone in patients with relapsed, platinum-sensitive ovarian cancer. Kaye, SB., Poole, CJ., Dańska-Bidzińska, A., et al.[2022]

Antibody-drug conjugates (ADCs) are a promising cancer treatment that selectively deliver toxic drugs to tumor cells by targeting specific antigens, which helps reduce systemic toxicity compared to traditional chemotherapy.

Over 15 ADCs are currently being studied for ovarian cancer, with some showing promising results in early-phase clinical trials, indicating their potential effectiveness in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-Drug Conjugates: A Promising Novel Therapy for the Treatment of Ovarian Cancer. Manzano, A., Ocaña, A.[2020]

Bevacizumab Vedotin, a novel antibody-drug conjugate, effectively targets tumors by combining the specificity of bevacizumab with the cytotoxic effects of MMAE, showing strong stability and tumor cell targeting in biological studies.

In vitro tests demonstrated that Bevacizumab Vedotin not only inhibits cancer cell proliferation and promotes apoptosis in various cancer cell lines but also enhances anti-migration activity and blocks the VEGF/VEGFR pathway, suggesting a promising therapeutic approach with potentially reduced systemic toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of novel antibody-drug conjugates bearing tissue protease specific linker with both anti-angiogenic and strong cytotoxic effects. Li, Y., Si, R., Wang, J., et al.[2023]

Antibody drug conjugates (ADCs) are a promising new way to deliver chemotherapy specifically to cancer cells, with over 15 ADCs currently being studied for efficacy in treating epithelial ovarian cancer.

While ADCs show promising results in trials, they have reported side effects such as visual disturbances and neuropathy, but they do not cause significant hematologic toxicity, making them a safer option compared to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody Drug Conjugates in the Treatment of Epithelial Ovarian Cancer. Richardson, DL., Seward, SM., Moore, KN.[2019]

Mirvetuximab Soravtansine (IMGN853) is an antibody drug conjugate that targets the folate receptor alpha and has shown promising effectiveness and a favorable safety profile in treating platinum-resistant ovarian cancer, particularly in patients with moderate-to-high FRα expression.

The ongoing phase III study comparing IMGN853 to standard chemotherapy aims to further establish its efficacy, while additional ADCs targeting other cancer markers are also being explored in early clinical trials, highlighting a growing strategy to enhance treatment for ovarian cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antibody-drug conjugates for ovarian cancer: current clinical development. Stewart, D., Cristea, M.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40491605/

Preclinical development of mecbotamab vedotin (BA3011) ... We developed a novel, conditionally active biologic ADC, mecbotamab vedotin (BA3011), which selectively binds to AXL in the acidic tumor microenvironment.

2. ir.bioatla.com ir.bioatla.com/news-releases/news-release-details/bioatla-present-clinical-data-mecbotamab-vedotin-ba3011-soft

BioAtla to Present Clinical Data for Mecbotamab Vedotin ... The presentation, titled “Median OS of 21.5 months among 44 patients with treatment-refractory leiomyosarcoma, liposarcoma, and undifferentiated ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03425279

NCT03425279 | CAB-AXL-ADC Safety and Efficacy Study ... The objective of this study is to assess the safety and efficacy of mecbotamab vedotin (BA3011) in solid tumors. Detailed Description. This is a multi-center, ...

4. ckb-core.genomenon.com ckb-core.genomenon.com/therapy/show/14916

Therapy Detail - CKB CORE - Genomenon Imfinzi (durvalumab) is a monoclonal antibody that binds to and inhibits PD-L1 (CD274), potentially resulting in increased immune response to tumors (PMID: ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12146481/

Preclinical development of mecbotamab vedotin (BA3011), a ... We developed a novel, conditionally active biologic ADC, mecbotamab vedotin (BA3011), which selectively binds to AXL in the acidic tumor microenvironment.

6. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03425279

NCT03425279 | CAB-AXL-ADC Safety and Efficacy Study ... The objective of this study is to assess the safety and efficacy of mecbotamab vedotin (BA3011) in solid tumors. Detailed Description. This is a multi-center, ...

7. ocrahope.org ocrahope.org/news/first-patients-dosed-in-phase-2-platform-clinical-trial-testing-novel-immunotherapy-combinations-in-highly-malignant-ovarian-cancer/

Trial Tests Immunotherapy Combo in Ovarian Cancer BioAtla's BA3011, CAB-AXL-ADC, is a conditionally and reversibly active antibody-drug conjugate targeting the receptor tyrosine kinase AXL that ...

8. ctg.queensu.ca ctg.queensu.ca/cctg_news/novel-immunotherapy-combinations-highly-malignant-ovarian-cancer

Novel immunotherapy combinations in highly malignant ... “The IPROC trial builds upon the results seen in positive immunotherapy combination studies in ovarian cancer, and was designed in collaboration ...