Dostarlimab vs Chemotherapy for Endometrial Cancer

(DOMENICA Trial)

Recruiting at 96 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

260 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Dostarlimab for endometrial cancer?

Dostarlimab, an immune-checkpoint inhibitor, may work well with chemotherapy to treat endometrial cancer, as suggested by research showing that combining chemotherapy and immunotherapy can have synergistic effects. Additionally, a study on paclitaxel and carboplatin, which are part of the chemotherapy regimen, showed a significant reduction in tumor size in 63% of patients with endometrial cancer. ^{1 2 3 4 5}

Is Dostarlimab or Carboplatin-Paclitaxel safe for treating endometrial cancer?

Dostarlimab has been studied for safety in patients with advanced or recurrent endometrial cancer, showing it is generally safe for use. Carboplatin and paclitaxel have been used in similar conditions, with some patients experiencing significant side effects like blood-related issues and nerve damage, but these were considered acceptable levels of toxicity. ^{1 2 3 4 5}

What makes the drug Dostarlimab unique for treating endometrial cancer?

Dostarlimab is unique because it is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor, potentially enhancing the effects of chemotherapy when combined with carboplatin and paclitaxel for endometrial cancer. This combination may offer a new approach for patients, especially those with mismatch repair-deficient or microsatellite instability-high advanced or recurrent endometrial cancer, where no clear standard treatment exists. ^{1 3 4 6 7}

What is the purpose of this trial?

Phase 3, randomized, multicentre study to evaluate the efficacy and safety of dostarlimab versus carboplatin-paclitaxel in patients with MMR deficient relapse or advanced endometrial cancer.

Research Team

Florence Joly, MD

Principal Investigator

Centre François Baclesse

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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]

References

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

Dostarlimab for Primary Advanced or Recurrent Endometrial Cancer. [2023]

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

A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report. [2016]

3. Germany pubmed.ncbi.nlm.nih.gov

Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study. [2022]

4. England 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. [2023]

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

Carboplatin and paclitaxel for the treatment of advanced or recurrent endometrial cancer. [2015]

6. England 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. [2023]

7. Germany 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. [2015]