Rina-S for Ovarian Cancer

(RAINFOL-02 Trial)

Recruiting at 83 trial locations

Overseen By Genmab Trial Information

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Genmab

Must be taking: Platinum chemotherapy, Bevacizumab, PARP inhibitors, Mirvetuximab

Must not be taking: Topoisomerase inhibitors

Disqualifiers: Platinum-refractory, CNS metastases, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 5 years

530 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the new treatment, Rina-S, surpasses existing chemotherapy options for individuals with platinum-resistant ovarian cancer. Participants will receive either Rina-S or one of four approved chemotherapy drugs, with treatment assignments kept secret until the first dose. Eligible participants should have high-grade serous or endometrioid ovarian cancer and have previously undergone at least one line of treatment that included platinum chemotherapy. Importantly, all participants will receive an active treatment, not a placebo. As a Phase 3 trial, this study represents the final step before FDA approval, offering access to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that Rina-S is generally well-tolerated. In earlier studies, patients using Rina-S did not experience serious eye or lung problems. The side effects that occurred were manageable, and no new safety issues emerged. This suggests that Rina-S could be a safe choice for many people, but discussing any possible risks with a doctor is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for ovarian cancer?

Researchers are excited about Rina-S for ovarian cancer because it potentially offers a novel approach compared to current treatments like chemotherapy and targeted therapies. Unlike many existing options that focus on broadly attacking cancer cells, Rina-S may work by a unique mechanism, specifically targeting molecular pathways linked to ovarian cancer progression. This targeted action could mean fewer side effects and improved efficacy, offering hope for better patient outcomes.

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

Research has shown that Rina-S, which participants in this trial may receive, may help treat advanced ovarian cancer. In one study, about 23 out of 100 patients who received Rina-S saw their tumors shrink. Another study found that half of the patients experienced a significant reduction in tumor size with Rina-S treatment. Some patients even had complete responses, where all signs of cancer disappeared. These early results suggest that Rina-S could be a strong option for those with ovarian cancer that doesn't respond to standard treatments. Participants in this trial may also receive treatment based on the investigator's choice, serving as an active comparator. ^{1 3 5 6 7}

Who Is on the Research Team?

Study Official

Principal Investigator

Genmab

Are You a Good Fit for This Trial?

This trial is for those with high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer who've had platinum-based therapy and are platinum-resistant. They must have positive FRα expression and no contraindications to bevacizumab unless documented. Those treated with PARP inhibitors due to BRCA mutations can join if mirvetuximab soravtansine is available locally.

Inclusion Criteria

I have received bevacizumab for my condition if it was recommended and available.

Participants may be enrolled regardless of FRα expression level

I have BRCA mutation and received a PARP inhibitor after responding to platinum-based chemotherapy.

Exclusion Criteria

I have been treated with a specific drug that targets cancer cells.

My cancer did not respond to initial platinum-based chemotherapy.

I have active brain metastases or carcinomatous meningitis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Rina-S or one of four chemotherapy agents as treatment for platinum-resistant ovarian cancer

Up to approximately 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Rina-S

Trial Overview The study compares Rina-S against standard chemotherapy drugs (PLD, Gemcitabine, Paclitaxel, Topotecan) for treating platinum-resistant ovarian cancer. Participants have a 50:50 chance of receiving either Rina-S or one of the chemotherapies without knowing which one until the first dose.

How Is the Trial Designed?

Group I: Rina-S Experimental Treatment 1 Intervention

Group II: Investigator's Choice Active Control 4 Interventions

Who Is Running the Clinical Trial?

Genmab

Lead Sponsor

Trials

76

Recruited

15,300+

Dr. Jan van de Winkel

Genmab

Chief Executive Officer since 2010

PhD in Immunology, University of Utrecht

Dr. Judith Klimovsky

Genmab

Chief Medical Officer since 2019

MD, University of Copenhagen

Published Research Related to This Trial

In a study of 19 ovarian cancer patients treated with olaparib over a median duration of 12 months, 95% experienced adverse events (AEs), with the most common being fatigue, nausea, and anemia, indicating that while AEs are prevalent, they are often manageable.

The study found that dose modifications for managing AEs were effective, with eight patients requiring dose adjustments and five successfully re-escalating their doses, suggesting that olaparib can be safely administered with careful monitoring and management of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olaparib dose re-escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series. Ngu, SF., Tse, KY., Chu, MMY., et al.[2021]

In women with platinum-sensitive recurrent ovarian cancer, BRCA mutations serve as a key predictive marker for targeted therapy, indicating that those with these mutations are more likely to benefit from PARP inhibitors like olaparib.

For patients without BRCA mutations, bevacizumab is currently the preferred maintenance therapy, emphasizing the importance of genetic screening to tailor treatment strategies and improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New perspective on maintenance therapies for platinum- sensitive recurrent ovarian cancer in women with germline and somatic mutations in BRCA1 and BRCA2 genes. Vergote, I., Bours, V., Blaumeiser, B., et al.[2023]

Olaparib significantly improves progression-free survival (PFS) in patients with platinum-sensitive BRCA-mutated ovarian cancer, with a hazard ratio of 0.31, indicating a strong benefit compared to placebo or chemotherapy.

The treatment also shows a slight improvement in overall survival (OS) with a hazard ratio of 0.75, while maintaining a manageable safety profile with mostly mild adverse effects like anemia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of olaparib maintenance therapy in platinum-sensitive ovarian cancer patients with BRCA mutations: a meta-analysis on randomized controlled trials. Ma, J., Deng, H., Li, J., et al.[2020]

The combination of olaparib and carboplatin is tolerable and shows clinical benefit in patients with BRCA wild-type high-grade serous ovarian carcinoma, with a clinical benefit rate of 64% in heavily pretreated patients.

The maximum tolerated dose was established at olaparib 400 mg twice daily with carboplatin AUC4, although significant side effects like neutropenia and thrombocytopenia were observed, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/Ib study of olaparib and carboplatin in heavily pretreated recurrent high-grade serous ovarian cancer at low genetic risk. Lampert, EJ., Hays, JL., Kohn, EC., et al.[2023]

In the TRINOVA-1 study involving 919 women with recurrent ovarian cancer, treatment with trebananib plus weekly paclitaxel significantly improved progression-free survival (PFS) compared to placebo, with PFS of 7.2 months versus 5.4 months.

Despite the improvement in PFS, the quality of life (HRQoL) for patients receiving trebananib remained stable, showing negligible changes in HRQoL scores over 25 weeks, indicating that the treatment did not compromise patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life in women with recurrent ovarian cancer receiving paclitaxel plus trebananib or placebo (TRINOVA-1). Fujiwara, K., Monk, BJ., Lhommé, C., et al.[2020]

Citations

1. onclive.com onclive.com/view/rina-s-displays-early-efficacy-in-advanced-ovarian-cancer

Rina-S Displays Early Efficacy in Advanced Ovarian Cancer Patients who received 100 mg/m 2 of Rina-S (n = 22) achieved a confirmed objective response rate (ORR) of 22.7% (95% CI, 7.8%-45.4%), including a 4.5% ...

2. ir.genmab.com ir.genmab.com/news-releases/news-release-details/genmab-announces-new-data-demonstrating-investigational

Genmab Announces New Data Demonstrating ... The study showed that at a median study follow-up of one year, treatment with Rina-S 100 mg/m² every 3 weeks (Q3W) resulted in a 50.0% ...

3. cancernetwork.com cancernetwork.com/view/rina-s-elicits-encouraging-antitumor-activity-in-advanced-ovarian-cancer

Rina-S Elicits Encouraging Antitumor Activity in Advanced ... Additionally, 4.5% and 11.1% of patients in each respective cohort achieved complete responses (CRs), and 18.2% and 44.4% had partial responses ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS5627

A phase 3, open-label, randomized study of rinatabart ... In cohort B1 of a phase 1/2 trial (NCT05579366), Rina-S 120 mg/m² every 3 weeks (Q3W) showed encouraging anti-tumor activity with a 50% ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06619236

NCT06619236 | Study to Assess the Efficacy of Rina-S ... The purpose of this study is to compare how well Rina-S works against platinum-resistant ovarian cancer compared to chemotherapy drugs that are already approved ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07225270

Study to Assess the Efficacy and Safety of Rina-S Plus ... The purpose of this study is to evaluate how well Rina-S works against ovarian cancer in combination (with) available standard of care therapy ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02300-7/fulltext

719MO A phase I/II study of rinatabart sesutecan (Rina-S) ... No ocular toxicity or interstitial lung disease was observed. The emerging safety profile of Rina-S in Part B is consistent with Part A. For Part A OC and EC ...