Dostarlimab vs Chemotherapy for Endometrial Cancer

(DOMENICA Trial)

Not currently recruiting at 119 trial locations

Overseen By Ophélie BACONNET

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: ARCAGY/ GINECO GROUP

Must not be taking: Anti-PD-1, Anti-PD-L1, Anti-PD-L2, Immunomodulatory agents

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, 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: 12-18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments to determine which is more effective for endometrial cancer that has recurred or spread. One group receives dostarlimab, a drug that helps the immune system fight cancer, while the other group receives standard chemotherapy with carboplatin and paclitaxel. The trial aims to identify which treatment is more effective and safer for patients. Women with advanced or recurrent endometrial cancer, specifically those with a tumor type known as MMR deficient, may be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering patients an opportunity to contribute to potentially groundbreaking treatment advancements.

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

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like systemic corticosteroids, interferons, interleukins, and live vaccines must be stopped at least 7 to 30 days before starting the study treatment.

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

Previous studies have shown that dostarlimab is quite safe for patients, particularly those with advanced or recurrent endometrial cancer. When combined with standard chemotherapy, it helped patients live longer without their cancer worsening.

Research has demonstrated that the combination of carboplatin and paclitaxel is well-tolerated by patients. This common ovarian cancer treatment often does not cause major side effects and does not require additional support, such as growth factors, to boost blood cells during treatment.

Both treatments in this trial have undergone prior testing, and their safety profiles are well-understood. They are generally safe, with manageable side effects for most patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about dostarlimab because it offers a novel approach to treating endometrial cancer. Unlike standard chemotherapy, which targets rapidly dividing cells indiscriminately, dostarlimab is an immunotherapy that works by blocking the PD-1 pathway, helping the immune system recognize and attack cancer cells more effectively. This targeted mechanism of action could potentially lead to fewer side effects and improved outcomes for patients. Additionally, dostarlimab is administered in a less frequent dosing schedule, which might enhance patient convenience and quality of life compared to traditional chemotherapy regimens.

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

This trial will compare the effectiveness of dostarlimab with the combination of carboplatin and paclitaxel for treating endometrial cancer. Research has shown that dostarlimab may be promising, particularly for patients with specific biomarkers (dMMR/MSI-H). Studies found that their cancer remained stable for an average of 30 months. Patients taking dostarlimab were more than twice as likely to prevent their cancer from worsening for at least two years compared to others.

In contrast, carboplatin and paclitaxel have been effectively used together for advanced endometrial cancer, with an average time of 24 months during which the cancer does not progress. Both treatments have shown significant potential, but they work differently and have different strengths. Participants in this trial will receive either dostarlimab or the carboplatin-paclitaxel combination to evaluate their effectiveness. ^{1 4 5 6 7}

Who Is on the Research Team?

Florence Joly, MD

Principal Investigator

Centre François Baclesse

Are You a Good Fit for This Trial?

This trial is for women over 18 with advanced or recurrent endometrial adenocarcinoma that hasn't been treated with chemotherapy for the recurrence. They must be able to follow the study plan, have an ECOG score of 0-1, and their cancer should be MMR deficient/MSI-H confirmed by tests.

Inclusion Criteria

Patient has signed the Informed Consent (ICF) and is able to comply with protocol requirements

Patient with evaluable disease according to RECIST 1.1

Patient must have a negative serum pregnancy test within 72 hours of the first dose of study medication, unless they are of nonchildbearing potential

Exclusion Criteria

Patient is pregnant or breastfeeding or is expecting to conceive children within the projected duration of the study

Patient has a known hypersensitivity to specific components or excipients

Patient has a known history of human immunodeficiency virus (HIV)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Dostarlimab or Carboplatin-Paclitaxel chemotherapy. Dostarlimab is administered every 3 weeks for 4 cycles, then every 6 weeks. Carboplatin-Paclitaxel is administered every 3 weeks for 6 cycles.

12-18 weeks

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment, with assessments up to 5 years.

5 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term, with monitoring for progression and survival.

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin-Paclitaxel
• Dostarlimab

Trial Overview The study compares Dostarlimab, a new treatment option, against the standard chemotherapy combo of Carboplatin-Paclitaxel in patients with specific genetic markers (MMRd/MSI-H) in endometrial cancer. It's a phase 3 trial conducted across multiple centers.

How Is the Trial Designed?

Group I: Arm B: Carboplatin AUC 5 or 6 plus Paclitaxel 175 mg/m2, every 3 weeks, 6 cycles. Experimental Treatment 1 Intervention

Group II: Arm A: Dostarlimab 500 mg, every 3 weeks, 4 cycles and then 1000 mg every 6 weeks Experimental Treatment 1 Intervention

Carboplatin-Paclitaxel is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Carboplatin-Paclitaxel for:

• Non-small cell lung cancer
• Ovarian cancer
• Cervical cancer
• Endometrial cancer
• Thymoma or thymic carcinoma

Approved in European Union as Carboplatin-Paclitaxel for:

• Non-small cell lung cancer
• Ovarian cancer
• Cervical cancer
• Endometrial cancer
• Thymoma or thymic carcinoma

Approved in Canada as Carboplatin-Paclitaxel for:

• Non-small cell lung cancer
• Ovarian cancer
• Cervical cancer
• Endometrial cancer

Who Is Running the Clinical Trial?

ARCAGY/ GINECO GROUP

Lead Sponsor

Trials

65

Recruited

16,600+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

The combination of paclitaxel and carboplatin showed promising activity in treating endometrial cancer resistant to standard therapies, with 63% of evaluable patients experiencing a significant reduction in tumor size.

While the treatment had acceptable toxicity levels, with some patients experiencing grade 3 or 4 hematologic issues, further follow-up is needed to assess long-term survival outcomes and the overall effectiveness of this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. Price, FV., Edwards, RP., Kelley, JL., et al.[2016]

In a study of 24 patients with metastatic or recurrent endometrial cancer, the combination of tislelizumab with carboplatin-paclitaxel showed a promising objective response rate of 62.5%, indicating effective treatment for this challenging condition.

The treatment was found to be safe, with no allergic reactions or treatment-related deaths reported, although half of the patients experienced moderate to severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study. Gao, FF., Zhang, XL., Chen, JL., et al.[2022]

In a phase 3 trial involving 494 patients with advanced or recurrent endometrial cancer, dostarlimab combined with chemotherapy significantly improved progression-free survival, especially in patients with mismatch repair-deficient (dMMR) tumors, showing a 61.4% survival rate at 24 months compared to 15.7% for placebo.

Overall survival at 24 months was also better with dostarlimab (71.3%) compared to placebo (56.0%), indicating its efficacy as a treatment option, although it was associated with a higher incidence of severe adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. Mirza, MR., Chase, DM., Slomovitz, BM., et al.[2023]

In a study of 18 patients with advanced or recurrent endometrial cancer, the combination of carboplatin and paclitaxel showed a high overall response rate of 63%, with 35% achieving a complete response.

The treatment demonstrated minimal toxicity, as no patients experienced severe side effects like neutropenia or significant vomiting, and the median survival time was 27 months, indicating it is a promising option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. Akram, T., Maseelall, P., Fanning, J.[2015]

The recommended dosage for TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) was established as tolerable, showing a response rate of 74% and a median overall survival of 37 months for patients with advanced primary endometrial carcinoma.

Adjuvant TEC therapy significantly improved prognosis compared to radiation therapy in completely resected stage III endometrial cancer cases, indicating its effectiveness as both a remission-induction and adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy for endometrial carcinoma (GOGO-EM1 study): TEC (paclitaxel, epirubicin, and carboplatin) is an effective remission-induction and adjuvant therapy. Egawa-Takata, T., Ueda, Y., Kuragaki, C., et al.[2015]

Dostarlimab demonstrated superior overall survival (OS) compared to doxorubicin in patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) advanced/recurrent endometrial cancer, with median OS not reached for dostarlimab versus 11.2 months for doxorubicin.

Dostarlimab also showed a better safety profile, with lower rates of grade ≥3 adverse events (48.1% for dostarlimab vs 78.3% for doxorubicin), indicating it may be a safer option for patients following platinum-based therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Indirect Comparison of the Efficacy and Safety of Dostarlimab and Doxorubicin for the Treatment of Advanced and Recurrent Endometrial Cancer. Mathews, C., Lorusso, D., Coleman, RL., et al.[2023]

In a review of three studies involving 1,431 patients, the addition of PD-1/PD-L1 inhibitors to standard chemotherapy (carboplatin and paclitaxel) significantly improved progression-free survival (PFS) and overall survival (OS) in patients with mismatch repair-deficient endometrial cancer.

However, this benefit was not observed in patients with mismatch repair-proficient tumors, indicating that the effectiveness of the combination therapy may depend on the specific genetic characteristics of the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel compared with carboplatin and paclitaxel in primary advanced or recurrent endometrial cancer: a systematic review and meta-analysis of randomized clinical trials. de Moraes, FCA., Pasqualotto, E., Lopes, LM., et al.[2023]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0002937805000037

Carboplatin and paclitaxel for the treatment of advanced or ... The median progression-free survival was 24 months, and the median survival was 27 months. This combination was well tolerated with minimal toxicity. Although ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7676887/

Carboplatin and Paclitaxel for Advanced Endometrial Cancer This was the first trial to show a survival advantage for combination chemotherapy in patients with measurable advanced or recurrent endometrial cancer. For ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10373231/

Looking Beyond Carboplatin and Paclitaxel for the ... Median OS was 37 months and 41 months, respectively (HR: 1.002; 90% CI: 0.9 to 1.12); median progression-free survival (PFS) was 13 months and 14 months, ...

4. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-023-11654-z

PD-1/PD-L1 inhibitors plus carboplatin and paclitaxel ... Immunotherapy plus carboplatin-paclitaxel increased significantly PFS and OS among patients with advanced or recurrent endometrial cancer.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24088479

Weekly Paclitaxel-Carboplatin Regimen in Patients With ... The objective of the study was to evaluate the response of weekly paclitaxel/ carboplatin in patients with primary advanced or recurrent endometrial cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00942357

Study Details | NCT00942357 | Carboplatin and Paclitaxel ... This randomized phase III trial studies carboplatin and paclitaxel to see how well they work with or without cisplatin and radiation therapy in treating ...

7. nrgoncology.org nrgoncology.org/Home/News/Post/nrg-oncology-trial-data-concludes-paclitaxel-and-carboplatin-should-be-considered-the-standard-of-care-as-first-line-treatment-for-women-with-uterine-carcinosarcoma

NRG Oncology Trial Data Concludes Paclitaxel and ... The median overall survival for women with UCS treated with paclitaxel and carboplatin was 37 months compared to 29 months for women treated ...