Dostarlimab + Chemotherapy for Endometrial Cancer

(RUBY Trial)

Recruiting at 179 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Tesaro, Inc.

Must not be taking: Anti-PD-1, Anti-PD-L1, PARP inhibitors

Disqualifiers: Multiple recurrences, Uncontrolled CNS metastases, others

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: 6 months

785 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a 2 part study. Part 1 is to evaluate the efficacy and safety of dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus placebo plus carboplatin-paclitaxel followed by placebo; and Part 2 is to evaluate the efficacy and safety of dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo in participants with recurrent or primary advanced (Stage III or IV) endometrial cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received certain cancer therapies within 21 days before starting the study, and you should not have had a live vaccine within 30 days before the first dose.

What data supports the effectiveness of the drug combination Dostarlimab and Chemotherapy for Endometrial Cancer?

Research suggests that combining chemotherapy with immunotherapy, like dostarlimab, may work well together to treat endometrial cancer. Dostarlimab has shown effectiveness in patients with specific types of advanced or recurrent endometrial cancer, and similar combinations with other drugs have been effective in improving outcomes. ^{1 2 3 4 5}

Is the combination of Dostarlimab and chemotherapy safe for humans?

Dostarlimab has been approved for certain types of endometrial cancer, and studies have looked at its safety when combined with chemotherapy drugs like carboplatin and paclitaxel. These studies suggest that the combination is generally safe, but as with any treatment, there can be side effects, and it's important to discuss these with your doctor. ^{1 2 3 5 6}

What makes the drug dostarlimab combined with chemotherapy unique for treating endometrial cancer?

The combination of dostarlimab, an immune-checkpoint inhibitor, with chemotherapy is unique because it may have synergistic effects, enhancing the treatment of endometrial cancer by targeting the immune system and cancer cells simultaneously. Dostarlimab specifically targets the PD-1 receptor, which can help the immune system better recognize and attack cancer cells, offering a novel approach compared to traditional chemotherapy alone. ^{1 2 7 8 9}

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

This trial is for women over 18 with advanced (Stage III or IV) or recurrent endometrial cancer. They should have an ECOG performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory and able to carry out work of a light nature. Participants must not have used certain cancer treatments recently, have controlled blood pressure, adequate organ function, and no history of certain other diseases.

Inclusion Criteria

My endometrial cancer is advanced and not likely cured by surgery or radiation alone.

I can take medication by mouth.

My cancer has returned for the first time and I haven't had any cancer drugs yet.

Exclusion Criteria

My endometrial cancer has come back more than once.

I have a serious heart condition.

I have a higher risk of bleeding due to other health conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive dostarlimab plus carboplatin-paclitaxel followed by dostarlimab or placebo plus carboplatin-paclitaxel followed by placebo

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 years

Treatment Details

Interventions

• Carboplatin
• Dostarlimab
• Niraparib
• Paclitaxel
• Placebo
• Placebo matching dostarlimab
• Placebo matching Niraparib

Trial Overview The study tests the effectiveness and safety of dostarlimab combined with chemotherapy drugs carboplatin-paclitaxel followed by either dostarlimab alone or together with niraparib versus placebo versions. The goal is to see if these combinations help those with advanced stages of endometrial cancer.

Participant Groups

Group I: Arm 1: Participants receiving dostarlimab + Carboplatin-paclitaxel followed by dostarlimab Active Control 3 Interventions

Group II: Arm 3: Participants receiving dostarlimab + carboplatin-paclitaxel followed by dostarlimab+niraparib Active Control 4 Interventions

Group III: Arm 4: Participants receiving placebo + carboplatin-paclitaxel followed by placebo Placebo Group 4 Interventions

Group IV: Arm 2: Participants receiving placebo + carboplatin-paclitaxel followed by placebo Placebo Group 3 Interventions

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

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Tesaro, Inc.

Lead Sponsor

Trials

57

Recruited

10,600+

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

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]

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 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 study of 122 patients with high and intermediate-high risk endometrial cancer, those treated with a dose dense regimen of paclitaxel plus carboplatin showed a significantly higher three-year progression-free survival (79.5%) compared to those on the standard three-weekly protocol (57.4%).

The dose dense protocol also resulted in fewer progression events and distant metastases, along with improved overall survival in advanced stage cases, while experiencing fewer complaints of musculoskeletal pain compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. Kogan, L., Laskov, I., Amajoud, Z., et al.[2022]

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]

Dostarlimab-gxly (Jemperli) has received accelerated approval from the FDA for treating adults with mismatch repair deficient recurrent or advanced endometrial cancer and solid tumors, indicating its potential effectiveness in these specific cancer types.

This approval highlights the importance of targeted therapies in oncology, particularly for patients with specific genetic markers that may influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. Aschenbrenner, DS.[2023]

Dostarlimab showed significant antitumor activity in patients with advanced endometrial cancer, achieving an objective response rate (ORR) of 43.5% in those with dMMR/MSI-H disease, compared to 14.1% in those with proficient/stable disease, indicating its potential effectiveness in specific cancer subtypes.

The treatment had a manageable safety profile, with most adverse events being mild to moderate (grade 1-2), and no deaths attributed to the drug, suggesting it is a safe option for patients with advanced endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. Oaknin, A., Gilbert, L., Tinker, AV., et al.[2022]

Dostarlimab, an investigational anti-PD-1 monoclonal antibody, shows promising clinical activity, especially in treating endometrial cancer, indicating its potential as a new treatment option.

This antibody is being explored both alone and in combination with other therapies for various cancers, including gynecological tumors, lung cancer, and melanoma, highlighting its broad applicability in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. Rubio-Pérez, J., Hernández, R., Hernández, T., et al.[2021]

References

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

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

2. 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]

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

Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. [2022]

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

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

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

New Drug for Mismatch Repair Deficient Endometrial Cancer and Solid Tumors. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET-a phase I, single-arm study. [2022]

8. Spain pubmed.ncbi.nlm.nih.gov

Dostarlimab for the treatment of endometrium cancer and other solid tumors. [2021]

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

Outcomes for Dostarlimab and Real-World Treatments in Post-platinum Patients With Advanced/Recurrent Endometrial Cancer: The GARNET Trial Versus a US Electronic Health Record-Based External Control Arm. [2023]