Trastuzumab Deruxtecan + Rilvegostomig/Pembrolizumab for Endometrial Cancer

(DE-01 Trial)

Recruiting at 177 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

Trial Summary

What is the purpose of this trial?

DESTINY-Endometrial01 will investigate the efficacy of first-line T-DXd + rilvegostomig (Arm A) and/or T-DXd+ pembrolizumab (Arm B) when compared to chemotherapy (carboplatin + paclitaxel) + pembrolizumab (Arm C), by assessment of progression free survival (PFS), as assessed by BICR, in participants with HER2-expressing (IHC 3+/2+), pMMR, primary advanced (Stage III/IV) or recurrent EC.

Eligibility Criteria

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

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

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

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

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

Treatment Details

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.

Participant Groups

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+