A Global Phase III Study of Puxitatug Samrotecan (AZD8205) Monotherapy Compared with Physician’s Choice of Chemotherapy for B7-H4-Selected Endometrial Cancer that Progressed Following Platinum-Based Chemotherapy and Anti-PD-1/Anti-PD-L1 Therapy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

11 Feb 2026 → ongoing

Decision date (initial)

2025-11-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2024-518777-34-00

ClinicalTrials.gov

NCT07044336

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Efficacy, Pharmacokinetic, Safety

- Progression Free Survival (PFS) for Arm A vs Arm B.
- Overall survival (OS) for Arm A vs Arm B.

Secondary objectives 7

1. Assessment of Overall Response Rate (ORR) for Arm A vs Arm B.
2. Assessment of Duration of response (DoR) for Arm A vs Arm B.
3. Assessment of progression-free survival 2 (PFS2) for Arm A vs Arm B.
4. Time until first subsequent anticancer therapy after discontinuation of the randomized treatment, or death (TFST) for Arm A vs Arm B.
5. Time until the second subsequent anticancer therapy after discontinuation of the first subsequent treatment, or death (TSST) for Arm A vs Arm B.
6. Time until discontinuation of treatment for any reason, or death (TDT) for Arm A vs Arm B.
7. Worsening in endometrial symptoms for Arm A vs Arm B.

Conditions and MedDRA coding

B7-H4-Selected Advanced/Metastatic Endometrial Cancer.

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-000024-PIP20-35

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Histologically confirmed diagnosis of endometrial carcinoma or carcinosarcoma.
2. Recurrent/metastatic EC ie, with radiological or objective evidence of recurrence or progression.
3. Has received prior platinum-based chemotherapy and anti-programmed cell death 1 protein (PD-1)/anti- programmed cell death ligand 1 (PD-L1) therapy, either separately or in combination.
4. A WHO/ECOG performance status of 0 or 1 at Screening.
5. Has radiographically measurable disease by RECIST 1.1

Exclusion criteria 7

1. Had uterine sarcomas or uterine neuroendocrine carcinoma.
2. Has had a recurrence of endometrial carcinoma or carcinosarcoma more than > 12 months after completing platinum-based therapy administered in the curative-intent setting without any additional platinum-based therapy received in the recurrent setting.
3. Had previously received treatment with any therapy (approved or investigational) that contained a TOP1i including ADCs.
4. Had previously received treatment with AZD8205 or another B7-H4 targeting agent.
5. History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
6. Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
7. Active or previously documented autoimmune or inflammatory disorders.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. PFS is defined as the time from randomization until progression per RECIST 1.1 as assessed by BICR or death due to any cause.
2. OS is defined as the time from randomization until the date of death due to any cause.

Secondary endpoints 7

1. ORR is defined as the proportion of participants who have a response of CR or PR, as determined by BICR assessments, per RECIST 1.1.
2. DoR will be defined as the time from the date of first documented response until the date of documented progression per RECIST 1.1 as assessed by BICR, or death due to any cause.
3. PFS2 will be defined as the time from randomization to the earliest of the progression event (following the initial Investigator-assessed progression), after first subsequent therapy, or death.
4. TFST is defined as the time from randomization until the start date of the first subsequent anticancer therapy after discontinuation of the randomized treatment, or death due to any cause.
5. TSST is defined as the time from randomization until the start date of the second subsequent anticancer therapy after discontinuation of the first subsequent treatment, or death due to any cause.
6. TDT is defined as the time from randomization until discontinuation of treatment for any reason, including disease progression, toxicity, and death.
7. Time to worsening is defined as time from date of randomization to the date of worsening while on treatment for endometrial symptoms, physical functioning, and health-related quality of life based on select items from the EORTC IL389.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

Clinical Study Information Center

Third parties 2

Locations

15 EU/EEA countries · 112 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 146 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

15 submissions — initial application plus substantial / non-substantial modifications