Puxitatug Samrotecan for Endometrial Cancer

Recruiting at 158 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must not be taking: TOP1i, B7-H4 agents

Disqualifiers: Uterine sarcomas, Neuroendocrine carcinoma, ILD, Autoimmune disorders, 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: 3

Duration: Approximately 3 years

700 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called puxitatug samrotecan for individuals with advanced or metastatic endometrial cancer (cancer of the uterine lining) that has not responded to standard treatments. The trial aims to evaluate the effectiveness and safety of this new treatment compared to current chemotherapy options, such as doxorubicin or paclitaxel. Participants will join one of two groups: one receiving puxitatug samrotecan and the other receiving chemotherapy. Ideal candidates have experienced cancer recurrence or progression after previous chemotherapy and immunotherapy. As a Phase 3 trial, this study serves as the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that puxitatug samrotecan has a manageable safety profile. In one study, most patients experienced some side effects, with 91.5% of patients having treatment-related side effects, many of which were mild. More serious side effects occurred in 55.3% of patients. These results align with those of other treatments. Overall, the treatment is considered to have manageable safety, indicating that while side effects are common, they can be controlled. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for endometrial cancer?

Unlike the standard chemotherapy treatments for endometrial cancer, which typically involve drugs like Doxorubicin and Paclitaxel, Puxitatug Samrotecan stands out due to its novel active ingredient. Puxitatug Samrotecan, also known as P-Sam, is an experimental drug administered intravenously every three weeks and is designed to target cancer cells more precisely. Researchers are particularly excited about P-Sam because it offers a new mechanism of action that could potentially improve treatment outcomes and reduce side effects compared to traditional chemotherapy options.

What evidence suggests that puxitatug samrotecan might be an effective treatment for endometrial cancer?

Research has shown that puxitatug samrotecan, which participants in this trial may receive, may effectively treat advanced endometrial cancer. In earlier studies, about 34.6% to 38.5% of patients experienced their cancer shrinking or stopping its growth, suggesting significant patient benefit. Early results also indicate that it might help patients live longer without their cancer worsening. This trial will compare puxitatug samrotecan with a chemotherapy arm, where participants will receive either Doxorubicin or Paclitaxel, to evaluate its effectiveness for patients who have not had success with other therapies, such as chemotherapy and anti-PD-1/PD-L1 treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Christian Marth, MD, PhD

Principal Investigator

Medical University of Innsbruck

Brian Slomovitz, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Stephanie Gaillard, MD, PhD

Principal Investigator

Johns Hopkins University - Sidney Kimmel Comprehensive Cancer Center (SKCCC)

Are You a Good Fit for This Trial?

This trial is for individuals with advanced or metastatic endometrial cancer that worsened after platinum-based chemotherapy and anti-PD-1/anti-PD-L1 therapy. Participants must have tumors selected for B7-H4 expression.

Inclusion Criteria

Has radiographically measurable disease by RECIST 1.1

I have been diagnosed with endometrial cancer or carcinosarcoma.

My cancer has come back or spread, confirmed by tests.

Exclusion Criteria

I have or had an autoimmune or inflammatory disorder.

I have been diagnosed with uterine sarcoma or neuroendocrine carcinoma.

My endometrial cancer returned over a year after finishing platinum therapy without receiving more platinum treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either AZD8205 IV Day 1 Q3W or chemotherapy (doxorubicin IV Q3W or paclitaxel IV on Days 1, 8, and 15 in 28-day cycles)

Approximately 3 years

Regular visits every 3 weeks for AZD8205 or every 28 days for chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Doxorubicin
• Paclitaxel
• Puxitatug Samrotecan

Trial Overview The study compares the effectiveness of Puxitatug Samrotecan, a new treatment, against standard chemotherapy options (doxorubicin or paclitaxel) in patients whose tumors express B7-H4.

How Is the Trial Designed?

Group I: Puxitatug Samrotecan Experimental Treatment 1 Intervention

P-Sam IV (intravenous) Q3W .

Group II: Chemotherapy Active Control 2 Interventions

Physician's choice of chemotherapy Doxorubicin IV Q3W or Paclitaxel IV on Days 1, 8, and 15 in 28 day cycles.

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

Citations

1. onclive.com onclive.com/view/puxitatug-samrotecan-demonstrates-efficacy-manageable-safety-in-advanced-metastatic-endometrial-cancer

Puxitatug Samrotecan Demonstrates Efficacy, ... - OncLive Puxitatug samrotecan demonstrated promising efficacy in endometrial cancer with objective response rates of 34.6% and 38.5% for 2.0 mg/kg and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07044336

Study Details | NCT07044336 | Puxitatug Samrotecan ... This study aims to see if puxitatug samrotecan allows participants to live longer without their endometrial cancer getting worse, or simply to live longer, ...

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D6900C00003

Puxitatug Samrotecan (AZD8205) Monotherapy vs ... This study aims to see if puxitatug samrotecan allows participants to live longer without their endometrial cancer getting worse, or simply to live longer, ...

4. healio.com healio.com/news/hematology-oncology/20250514/video-puxitatug-samrotecan-shows-promise-for-patients-with-recurrent-endometrial-cancer

VIDEO: Puxitatug samrotecan shows promise for patients ... Matulonis, MD, discusses preliminary efficacy and safety results for puxitatug samrotecan in patients with recurrent endometrial cancer.

5. mdanderson.org mdanderson.org/newsroom/novel-adc-azd8205-demonstrates-manageable-safety-profile-and-preliminary-efficacy-in-first-in-human-trial.h00-159700701.html

ESMO: Novel ADC AZD8205 demonstrates manageable ... This first-in-human trial with AZD8205 demonstrated promising clinical activity, especially in gynecologic tumors and breast cancer, and a safety profile ...

6. gynecologiconcology-online.net gynecologiconcology-online.net/article/S0090-8258(25)00713-9/abstract

Safety and preliminary efficacy of puxitatug samrotecan ... Safety and preliminary efficacy of puxitatug samrotecan (AZD8205) in patients with endometrial cancer: A first-in-human phase I/IIa study. Stephanie Gaillard.

7. ascopost.com ascopost.com/news/september-2024/novel-antibody-drug-conjugate-puxitatug-samrotecan-may-demonstrate-manageable-safety-profile-and-preliminary-efficacy-in-first-in-human-trial/

Novel Antibody Drug Conjugate Puxitatug Samrotecan ... The researchers reported that 91.5% of the patients experienced treatment-related adverse events of any grade and 55.3% of them experienced ...