Trastuzumab Deruxtecan + Rilvegostomig/Pembrolizumab for Endometrial Cancer

(DE-01 Trial)

Recruiting at 242 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Organ transplant, 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 24 months

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of two new treatment combinations for endometrial cancer that has progressed or returned after prior treatment. Researchers are comparing two experimental treatments: one combines trastuzumab deruxtecan (a targeted therapy) with rilvegostomig, and the other with pembrolizumab (an immunotherapy), against a standard chemotherapy regimen. Participants should have advanced or recurrent endometrial cancer with specific traits, such as HER2 expression, and must not have received certain types of cancer treatments before. As a Phase 3 trial, this study represents the final step before FDA approval, offering patients access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, any concurrent anticancer treatment requires an adequate washout period (time without taking certain medications) before starting the study. Hormonal therapy for non-cancer-related conditions is allowed.

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

Previous studies have shown that trastuzumab deruxtecan (T-DXd) has a safety profile consistent with existing knowledge of the drug, including some risk of lung-related side effects, which are being closely monitored. Research involving T-DXd combined with rilvegostomig has not revealed any unexpected safety issues. Similarly, combining T-DXd with pembrolizumab produced safety results consistent with earlier studies.

Pembrolizumab, another component of the treatment, has FDA approval for other conditions, providing some confidence in its safety. The trial is studying the combination treatments for their effectiveness and safety in people with endometrial cancer. Although these treatments are still under investigation, their late-stage study status suggests they are generally well-tolerated. Safety will continue to be monitored throughout the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Trastuzumab Deruxtecan (T-DXd) combined with Rilvegostomig or Pembrolizumab for endometrial cancer because these combinations offer innovative approaches beyond the current standard treatments like Carboplatin and Paclitaxel. T-DXd is an antibody-drug conjugate that delivers cancer-killing agents directly to cancer cells, potentially increasing effectiveness while minimizing damage to healthy cells. When combined with Rilvegostomig, which targets specific receptors on cancer cells, this offers a dual-action approach to tackle the disease. The combination with Pembrolizumab, an immunotherapy drug, might enhance the immune system's ability to attack cancer cells. These novel combinations promise to improve outcomes by using targeted therapies and boosting the body's natural defenses against cancer.

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

Studies have shown that Trastuzumab Deruxtecan (T-DXd) effectively treats endometrial cancer with high HER2 levels, achieving a 57.5% response rate in previous patients. This trial will evaluate T-DXd in combination with other drugs. In Arm A, participants will receive T-DXd combined with Rilvegostomig to assess whether this combination can improve results. Meanwhile, Arm B will test T-DXd with Pembrolizumab. Early findings are encouraging and suggest these combinations might outperform current treatments. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced (Stage III/IV) or recurrent HER2-expressing, pMMR endometrial cancer. Participants must not have had prior treatment for their condition and should be able to undergo procedures like biopsies.

Inclusion Criteria

Left ventricular ejection fraction (LVEF) ≥ 50% within 28 days before randomization.

I can provide a tissue sample from a tumor that hasn't been treated with radiation for testing.

I am 18 years old or older.

Exclusion Criteria

I have or might have lung inflammation that imaging tests could not rule out.

I have had an organ transplant.

I do not have any serious ongoing illnesses or infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive T-DXd plus rilvegostomig or pembrolizumab, or chemotherapy plus pembrolizumab, with treatment continuing until disease progression or other discontinuation criteria are met

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 45 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Docetaxel
• Paclitaxel
• Pembrolizumab
• Rilvegostomig
• Trastuzumab Deruxtecan

Trial Overview

The study compares the effectiveness of Trastuzumab Deruxtecan combined with either Rilvegostomig or Pembrolizumab against standard chemotherapy plus Pembrolizumab in preventing cancer progression.

How Is the Trial Designed?

Group I: Arm B: T-DXd + Pembrolizumab Experimental Treatment 2 Interventions

T-DXd IV Q3W plus pembrolizumab IV Q3W. Treatment will continue until objective disease progression according to RECIST v1.1 as assessed by the Investigator and confirmed by BICR or until other discontinuation criteria is met, whichever occurs first.

Group II: Arm A: T-DXd + Rilvegostomig Experimental Treatment 2 Interventions

T-DXd IV Q3W plus rilvegostomig IV Q3W. Treatment will continue until objective disease progression according to RECIST v1.1 as assessed by the Investigator and confirmed by BICR or until other discontinuation criteria is met, whichever occurs first.

Group III: Arm C: Carboplatin + Paclitaxel + Pembrolizumab Active Control 4 Interventions

Carboplatin, paclitaxel and pembrolizumab administered Q3W during 6 cycles, followed by maintenance with pembrolizumab IV Q6W during 14 cycles. Treatment with pembrolizumab will continue for up to 20 total cycles (approximately 24 months, accounting for combination and maintenance phases) or until other discontinuation criteria is met, whichever occurs first. At the discretion of the investigator, participants may continue to receive carboplatin, paclitaxel and pembrolizumab Q3W for up to 10 cycles. Docetaxel can be used as an alternative to paclitaxel for participants who had a hypersensitivity reaction to paclitaxel with a failed rechallenge (or not amenable to rechallenge), according to the investigator's clinical judgment.

Who Is Running the Clinical Trial?

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Daiichi Sankyo Co., Ltd.

Industry Sponsor

Trials

116

Recruited

49,200+

Gynecologic Oncology Group (GOG) Foundation Inc.

Collaborator

European Network for Gynaecological Oncological Trial groups(ENGOT)

Collaborator

Trials

1

Recruited

710+

Citations

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daiichisankyo.us

daiichisankyo.us/press-releases/-/article/destiny-endometrial01-phase-3-trial-of-enhertu-initiated-as-first-line-therapy-in-patients-with-her2-expressing-primary-advanced-or-recurrent-endometrial-cancer

DESTINY-Endometrial01 Phase 3 Trial of ENHERTU® ...

DESTINY-Endometrial01 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) ...

2.

ascopubs.org

ascopubs.org/doi/10.1200/JCO.23.02005

Efficacy and Safety of Trastuzumab Deruxtecan in Patients ...

Our study demonstrates durable clinical benefit, meaningful survival outcomes, and safety consistent with the known profile (including ILD) in pretreated ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06989112

DESTINY-Endometrial01: A Phase III Study of Trastuzumab ...

Treatment with pembrolizumab will continue for up to 20 total cycles (approximately 24 months, accounting for combination and maintenance phases) or until other ...

4.

sciencedirect.com

sciencedirect.com/science/article/pii/S2352578925002991

Successful treatment of gynecologic malignancy with ...

The objective response rate (ORR) was 57.5 % for endometrial cancer patients, 50.0 % for cervical cancer patients, and 45.0 % for ovarian cancer ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11622448/

Real-world evidence of Trastuzumab Deruxtecan (T-DXd) ...

Trastuzumab-Deruxtecan (T-DXd) has shown substantial efficacy in HER2 overexpressing carcinomas, most prominently in ovarian, endometrial and cervical patients.

6.

daiichisankyo.com

daiichisankyo.com/files/news/pressrelease/pdf/202506/20250609_E.pdf

DESTINY-Endometrial01 Phase 3 Trial of ENHERTU ...

DESTINY-Endometrial01 is a global, multicenter, randomized, open-label phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12215578/

Drug discovery in advanced and recurrent endometrial cancer

Results of the dMMR group demonstrated a 70% reduction in the risk of disease progression or death in patients who received pembrolizumab compared to placebo ( ...

8.

datasourcebydaiichisankyo.com

datasourcebydaiichisankyo.com/en/clinical-trials/-/view/study/NCT06989112

Clinical Trials

DESTINY-Endometrial01: A Phase III Study of Trastuzumab Deruxtecan Plus Rilvegostomig or Pembrolizumab as First-Line Treatment of HER2 ...