Navtemadlin for Endometrial Cancer

Recruiting at 93 trial locations

Overseen By John Mei

Age: 18+

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: Kartos Therapeutics, Inc.

Disqualifiers: Sarcomas, Small-cell carcinomas, Organ transplant, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

268 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called navtemadlin for individuals with advanced or recurring endometrial cancer who have responded well to chemotherapy. The study consists of two parts: the first part determines the best dose of navtemadlin by testing two different doses and comparing them to an observational group. The second part evaluates the effectiveness of this chosen dose against a placebo (a non-active substance). This trial suits those diagnosed with endometrial cancer, who have completed chemotherapy, and are in either complete or partial remission. As a Phase 2/3 trial, it focuses on measuring the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications for the trial?

The trial information does not specify if 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 navtemadlin, also known as AMG 232, is generally safe for humans at doses up to 240 mg. In earlier studies, patients tolerated this medication well, experiencing only mild to moderate side effects. Most side effects were manageable and not serious. This suggests that navtemadlin could be a safe option for patients with advanced or recurring endometrial cancer. However, discussing potential risks with a doctor remains important for any treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Navtemadlin for endometrial cancer because it offers a new approach by targeting the MDM2-p53 pathway, which is crucial for cancer cell growth and survival. Unlike traditional chemotherapy that attacks rapidly dividing cells, Navtemadlin specifically disrupts this pathway, potentially leading to fewer side effects. Additionally, Navtemadlin is administered orally, providing a convenient alternative to intravenous treatments, which can be more cumbersome and time-consuming for patients. These unique features make Navtemadlin a promising candidate in the fight against endometrial cancer.

What evidence suggests that navtemadlin could be an effective treatment for endometrial cancer?

Research shows that navtemadlin, one of the treatments studied in this trial, may help treat advanced or recurring endometrial cancer. It blocks a protein that aids cancer cell growth. Laboratory studies have found navtemadlin effective, especially when the TP53 gene functions properly. This gene controls cell growth and death. In early studies, patients tolerated navtemadlin well and showed positive responses. While more research is needed, these results suggest navtemadlin could be a helpful ongoing treatment for endometrial cancer. Participants in this trial may receive navtemadlin at different dosages or a placebo, as part of the various treatment arms. ^{5 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for patients with advanced or recurrent endometrial cancer who responded well to a specific chemo. They must have normal TP53 genes, good performance status (ECOG 0-1), and proper blood, liver, and kidney function. It's not for those with recent major bleeding, organ transplants, certain other cancers, recent experimental therapies or immune/cytokine therapy.

Inclusion Criteria

My endometrial cancer is confirmed and does not have TP53 mutations.

I completed a specific chemotherapy and my cancer responded well.

My blood, liver, and kidney functions are all within normal ranges.

Exclusion Criteria

I haven't had major bleeding or brain bleeding in the last 6 months.

My cancer is a type of sarcoma or has small-cell features with neuroendocrine traits.

I currently have surgical drains in place.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Evaluation of safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose

12 months

Monthly visits for safety and efficacy assessment

Treatment Part 2

Evaluation of the efficacy and safety of navtemadlin Phase 3 dose compared to placebo

50 months

Monthly visits for progression-free survival assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Navtemadlin
• Navtemadlin Placebo

Trial Overview The study tests navtemadlin as a maintenance treatment after chemotherapy success in two parts: first to find the best dose comparing two levels of navtemadlin against observation; second to compare that dose's effectiveness and safety against a placebo.

How Is the Trial Designed?

Group I: Part 2 Arm B Experimental Treatment 1 Intervention

Navtemadlin administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Group II: Part 2 Arm A Experimental Treatment 1 Intervention

Navtemadlin administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Group III: Part 1 Arm 2 Experimental Treatment 1 Intervention

Navtemadlin administered orally at 240 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Group IV: Part 1 Arm 1 Experimental Treatment 1 Intervention

Navtemadlin administered orally at 180 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.

Group V: Part 1 Arm 3 Active Control 1 Intervention

Observational control ("watch and wait") on a 28-day cycle.

Group VI: Part 2 Arm D Placebo Group 1 Intervention

Placebo administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.

Group VII: Part 2 Arm C Placebo Group 1 Intervention

Placebo administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.

Who Is Running the Clinical Trial?

Kartos Therapeutics, Inc.

Lead Sponsor

Trials

17

Recruited

2,100+

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05797831?term=AREA%5BInterventionSearch%5D(NAVTEMADLIN)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=1

Study of Navtemadlin as Maintenance Therapy in TP53WT ... This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12402800/

Preclinical Modeling of Navtemadlin Pharmacokinetics ... Navtemadlin (KRT-232) is a potent small-molecule MDM2 inhibitor, which has completed first-in-human studies (12) and advanced to phase II/III trials in ...

3. nature.com nature.com/articles/s41698-025-01063-9

Synergistic effect of MDM2 inhibitors and radiotherapy in ... AMG-232 is synergistic with radiotherapy in a xenograft model of wild-type TP53 endometrial cancer. To assess the in vivo efficacy of this ...

4. international-journal-of-gynecological-cancer.com international-journal-of-gynecological-cancer.com/article/S1048-891X(24)10862-6/pdf

a phase 2/3 study of navtemadlin as maintenance therapy ... KRT-232–118 is a Global 2-part Phase 2/3 study evaluating the safety and efficacy of navtemadlin as maintenance therapy in TP53WT advanced/recurrent EC patients ...

5. researchgate.net researchgate.net/publication/375506537_TP0081500_Trial_in_progress_phase_23_study_of_navtemadlin_as_maintenance_therapy_in_patients_with_advanced_or_recurrent_endometrial_cancer_who_responded_to_chemotherapy_ENGOT-EN21_GOG-3089

phase 2/3 study of navtemadlin as maintenance therapy in ... Introduction Advanced/recurrent endometrial cancer (EC) has poor prognosis with 5-year survival rate of ~17% (Colombo 2016; Siegel 2022).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05797831

NCT05797831 | Study of Navtemadlin as Maintenance ... This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24118026

phase 2/3 study of navtemadlin as maintenance therapy in ... KRT-232–118 is a Global 2-part Phase 2/3 study evaluating the safety and efficacy of navtemadlin maintenance therapy in TP53WT advanced/recurrent EC patients ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7211202/

Phase 1 study of the MDM2 inhibitor AMG 232 in patients with ... Safety, pharmacokinetics, pharmacodynamics, and efficacy were assessed. Results AMG 232 had acceptable safety up to up to 240 mg. Three ...

9. medchemexpress.com medchemexpress.com/AMG-232.html?srsltid=AfmBOoq_hZq4g9QxD7etBNMAmIsX7pC5cGlpty0xnDA6iYGLBIWRMyGp

Navtemadlin (AMG 232) | MDM2-p53 Interaction Inhibitor Navtemadlin (AMG 232) (10 μM) induces p53 signaling and inhibits tumor cell proliferation in three p53 wild-type tumor cell lines. Navtemadlin potently inhibits ...