Pembrolizumab + Chemotherapy for Endometrial Cancer

Not currently recruiting at 453 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Systemic steroids

Disqualifiers: Autoimmune disease, Pneumonitis, Liver disease, 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: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for endometrial cancer, which affects the lining of the uterus. Researchers aim to determine if adding pembrolizumab, an immunotherapy that helps the immune system fight cancer, to standard chemotherapy drugs (paclitaxel and carboplatin) is more effective than using the chemotherapy drugs alone. The trial focuses on individuals with stage III or IV endometrial cancer or those whose cancer has returned after improvement. Ideal candidates have measurable or recurrent endometrial cancer, have not received prior chemotherapy, or had their last chemotherapy over a year ago. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy or other immunosuppressive treatments, you must stop them at least 7 days before registration, unless they are inhaled, topical, or physiologic doses of corticosteroids.

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

Earlier studies have shown encouraging results when adding pembrolizumab to the usual chemotherapy drugs paclitaxel and carboplatin for endometrial cancer. Research indicates that patients generally tolerated this combination well. Some studies found that it slowed the spread and growth of cancer compared to chemotherapy alone.

While pembrolizumab is a newer addition to this treatment mix, the FDA has already approved it for other types of cancer, indicating its well-known safety profile. Most patients experienced common cancer treatment side effects, such as tiredness or nausea, while serious side effects were less common.

Although more research is needed to fully understand the benefits and risks, current evidence suggests that this combination is reasonably safe for use. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for endometrial cancer?

Researchers are excited about pembrolizumab combined with chemotherapy for endometrial cancer because it introduces a novel approach compared to traditional treatments. While standard therapies usually rely on chemotherapy alone, pembrolizumab is an immunotherapy that works by blocking the PD-1 pathway, which helps the immune system recognize and attack cancer cells more effectively. This combination aims to enhance the body's natural defenses against cancer alongside the powerful effects of chemotherapy, potentially leading to better outcomes for patients with this condition.

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

Research has shown that adding pembrolizumab to chemotherapy might help patients with advanced endometrial cancer. In this trial, participants in Arm II will receive pembrolizumab with chemotherapy, while those in Arm I will receive a placebo with chemotherapy. One study found that patients who received pembrolizumab with chemotherapy lived for about 13.1 months without their cancer worsening, compared to 8.7 months for those who received a placebo with chemotherapy. This indicates they lived longer without their cancer progressing. Another study found that 46% of patients experienced tumor shrinkage after receiving pembrolizumab with chemotherapy. These findings suggest that pembrolizumab, when combined with chemotherapy, could be a more effective treatment for this type of cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Ramez N Eskander

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for adults with stage III-IV or recurrent endometrial cancer. Eligible participants may have had prior hormonal therapy, but not chemotherapy for this cancer within the last year, and no previous treatment with certain immunotherapy drugs. They must not be pregnant, agree to use contraception if of childbearing potential, and cannot have severe allergies to the study drugs or significant health conditions that could affect safety.

Inclusion Criteria

My endometrial cancer is at stage III, IVA, IVB, or is recurrent.

I am HIV positive, on treatment, and my viral load is undetectable.

For patients of child bearing potential: negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is required

Exclusion Criteria

My hepatitis B virus load is undetectable with treatment.

I have not taken steroids or immunosuppressants in the last 7 days.

I do not have any severe illnesses that could interfere with the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Combination Phase

Patients receive pembrolizumab or placebo, paclitaxel, and carboplatin every 3 weeks for 6 cycles. Treatment may continue up to 10 cycles if necessary.

18-30 weeks

1 visit every 3 weeks

Maintenance Phase

Patients receive pembrolizumab or placebo every 6 weeks for up to 14 cycles.

84 weeks

1 visit every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Paclitaxel
• Pembrolizumab

Trial Overview The trial tests adding pembrolizumab (an immunotherapy drug) to the usual chemotherapy regimen of paclitaxel and carboplatin in treating advanced or recurrent endometrial cancer. It aims to see if this combination improves outcomes compared to chemotherapy alone.

How Is the Trial Designed?

Group I: Arm II (pembrolizumab, paclitaxel, carboplatin) Experimental Treatment 6 Interventions

COMBINATION PHASE: Patients receive pembrolizumab IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive pembrolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan throughout the study.

Group II: Arm I (placebo, paclitaxel, carboplatin) Active Control 6 Interventions

COMBINATION PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle, paclitaxel IV over 3 hours on day 1 of each cycle, and carboplatin IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 3 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients with SD or PR who still have measurable disease may continue treatment for up to a total of 10 cycles (if deemed necessary by the treating physician) in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Patients receive placebo IV over 30 minutes on day 1 of each cycle. Treatment repeats every 6 weeks for up to 14 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan throughout the study. On February 6, 2023, all patient treatment assignments were unblinded. Patients randomized to Arm 1 will not receive additional placebo infusions.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Canadian Cancer Trials Group

Collaborator

Trials

135

Recruited

70,300+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

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]

In a phase II study involving 46 patients with advanced endometrial cancer, the combination of pembrolizumab with carboplatin and paclitaxel resulted in a high objective response rate (ORR) of 74.4%, significantly exceeding the historical control rate of 50%.

The treatment was generally well-tolerated, with common mild side effects like anemia and fatigue, while immune profiling indicated that responders had enriched CD8+ and CD4+ T cell populations, suggesting a potential mechanism of action related to immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Biological Activity of Chemoimmunotherapy in Advanced Endometrial Adenocarcinoma: A Phase II Trial of the Big Ten Cancer Research Consortium. Barber, EL., Chen, S., Pineda, MJ., et al.[2023]

In the KEYNOTE-158 study, pembrolizumab showed a clinically meaningful objective response rate in patients with advanced MSI-H/dMMR endometrial cancer, with 84 out of 90 patients completing health-related quality of life (HRQoL) assessments.

Patients receiving pembrolizumab experienced significant improvements in their quality of life, with mean scores on the QLQ-C30 and EQ-5D-3L questionnaires increasing notably, especially among those who achieved a complete or partial response to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life with pembrolizumab monotherapy in patients with previously treated advanced microsatellite instability high/mismatch repair deficient endometrial cancer in the KEYNOTE-158 study. O'Malley, DM., Bariani, GM., Cassier, PA., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

In a phase 2 trial involving 125 women with advanced or recurrent endometrial cancer, adding avelumab to standard chemotherapy (carboplatin and paclitaxel) showed a similar median progression-free survival of 9.6 months compared to 9.9 months for chemotherapy alone, suggesting no significant improvement in efficacy.

However, the experimental group receiving avelumab experienced more serious adverse events, indicating potential safety concerns that need to be addressed in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel plus avelumab compared with carboplatin and paclitaxel in advanced or recurrent endometrial cancer (MITO END-3): a multicentre, open-label, randomised, controlled, phase 2 trial. Pignata, S., Scambia, G., Schettino, C., et al.[2023]

In a phase 3 trial involving 816 patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy (paclitaxel plus carboplatin) significantly improved progression-free survival, especially in patients with mismatch repair-deficient (dMMR) tumors, showing a 70% reduction in the risk of progression or death.

For patients with mismatch repair-proficient (pMMR) tumors, pembrolizumab also enhanced progression-free survival compared to placebo, indicating its efficacy across different tumor types, while the safety profile was consistent with known effects of pembrolizumab and chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus Chemotherapy in Advanced Endometrial Cancer. Eskander, RN., Sill, MW., Beffa, L., et al.[2023]

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2302312

Pembrolizumab plus Chemotherapy in Advanced ... In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P ...

2. keytruda.com keytruda.com/advanced-endometrial-cancer/clinical-trial-results-after-chemotherapy/

results from a clinical trial of keytruda after chemotherapy KEYTRUDA may help shrink tumors in adults with certain types of advanced endometrial cancer · 46% of 90 adults responded to therapy and saw their tumors either ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8527559/

Pembrolizumab in endometrial cancer: Where we stand now Indeed, 5-year survival ranges from 91% for FIGO IA disease to as low as 47% for FIGO IIIC and 17% for FIGO IV disease. Chemotherapy with carboplatin plus ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41009360/

The Efficacy of Pembrolizumab Immunotherapy in ... The results suggest a potential long-term treatment effect, although the limitations of the RCT and the variability in the therapeutic regimens ...

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/endometrial-cancer-durvalumab-pembrolizumab-chemotherapy

Imfinzi, Keytruda Approved for Some Endometrial Cancers The most recent data from the clinical trial that led to the dostarlimab approval, called RUBY, showed that it improved overall survival for ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05173987

NCT05173987 | Study of Pembrolizumab (MK-3475) ... The primary study hypotheses are that pembrolizumab is superior to the combination of carboplatin and paclitaxel with respect to Progression Free Survival (PFS) ...

7. keytruda.com keytruda.com/advanced-endometrial-cancer/clinical-trial-results-with-carboplatin-and-paclitaxel/

results from a clinical trial with KEYTRUDA with the chemotherapy medicines carboplatin and paclitaxel followed by KEYTRUDA alone was shown to reduce the risk of cancer spreading, growing, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9648489/

A Phase II Trial of the Big Ten Cancer Research Consortium Addition of pembrolizumab to carboplatin and paclitaxel for advanced endometrial cancer was tolerated and improved ORR compared with historical outcomes.

9. keytrudahcp.com keytrudahcp.com/efficacy/advanced-or-recurrent-endometrial-carcinoma/

KEYNOTE-868 - Clinical Trial Results & Study Design | HCP Health care professionals may find information about KEYNOTE-868 including clinical study results, study design, and safety profile. Explore here.