Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer

Endometrial Cancer Clinical Trial

Official title:

A Phase 2/3 Study of Navtemadlin as Maintenance Therapy in Subjects With TP53WT Advanced or Recurrent Endometrial Cancer Who Responded to Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05797831
• Other study ID #: KRT-232-118
• Secondary ID: ENGOT en-21GOG-3
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 17, 2023
• Est. completion date: July 2027

Study information

• Verified date: April 2024
• Source: Kartos Therapeutics, Inc.
• Contact: John Mei
• Phone: 650-542-0136
• Email: jmei[@]kartosthera.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates navtemadlin as maintenance treatment for patients with advanced or recurrent endometrial cancer (EC) who have achieved complete response or partial response on chemotherapy. The study will be conducted in 2 parts. Part 1 will evaluate safety and efficacy of two different doses of navtemadlin alongside an observational control arm to determine the Phase 3 navtemadlin dose. Part 2 will evaluate the efficacy and safety of navtemadlin Phase 3 dose compared to placebo.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 268
• Est. completion date: July 2027
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• ECOG 0-1
• Histologically or cytologically confirmed diagnosis of endometrial cancer documented as TP53WT
• Subjects with advanced or recurrent disease must have completed a single line of up to 6 cycles of taxane-platinum based chemo and achieved a CR or PR per RECIST V1.1
• Adequate hematologic, hepatic and renal function (within 14 days)

Exclusion Criteria:

• Has any sarcomas or small-cell carcinomas with neuroendocrine differentiation
• Prior immune therapy, cytokine therapy, or any investigational therapy (within 28 days)
• Indwelling surgical drains
• Grade 2 or higher QTc prolongation
• History of major organ transplant
• History of bleeding diathesis; major hemorrhage or intracranial hemorrhage (within 24 weeks)

Related Conditions & MeSH terms

• Endometrial Cancer
• Endometrial Neoplasms

Intervention

Drug:
• Navtemadlin
Navtemadlin is an experimental MDM2 anticancer drug taken by mouth
• Navtemadlin Placebo
Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth

Locations

Country	Name	City	State
Austria	University Hospital Graz, Department of Gynecology and Obstetrics	Graz
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	Medizinische Universität Wien	Vienna
Canada	Cross Cancer Institute	Edmonton
Canada	CHUM - University of Montreal Hospital Centre	Montreal
Denmark	Odense University Hospital	Odense
Estonia	Tartu University Hospital	Tartu
Finland	Kuopio University Hospital	Kuopio
Finland	Turku University Hospital	Turku
Georgia	LTD High Technology hospital Medcenter	Batumi
Georgia	American Hospital Network LLC	Tbilisi
Georgia	Caucasus Medical Centre	Tbilisi
Hungary	National Institute of Oncology	Budapest
Hungary	University of Debrecen Clinical Center	Debrecen
Israel	Rambam Medical Center	Haifa
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	Sourasky Medical Center	Tel-Aviv
Italy	A.O. Cannizzaro	Catania
Italy	IRCCS Istituto Romangolo per lo Studio dei Tumori "Dino Amadori"	Forli
Italy	Ospedale Policlinico San Martino	Genoa
Italy	ASST di Lecco-Ospedale Alessandro Manzoni	Lecco
Italy	Ospedale San Luca	Lucca
Italy	Osp. Niguarda	Milan
Italy	University Hospital of Parma	Parma
Italy	Ospedale Guglielmo da Saliceto	Piacenza
Italy	Ospedale di Prato S. Stefano	Prato
Italy	Ospedale Santa Maria delle Croci	Ravenna
Italy	"Azienda Unità Sanitaria Locale della Romagna - Hospital ""Infermi"" of Rimini Oncology Department"	Rimini
Italy	Policlinico Umberto	Rome
Italy	Ospedale Filippo Del Ponte	Varese
Lithuania	Health Sciences Kaunas Clinics	Kaunas
Lithuania	Nation Cancer Institute of Lithuania, Vilnius	Vilnius
Norway	Southern Hospital Sorlandet	Kristiansand
Norway	Oslo University Hospital HF	Oslo
Norway	Sykehusapotek Nord Tromsø	Tromsø
Poland	Bialostockie Centrum Onkologii	Bialystok
Poland	Szpitale Pomorskie	Gdansk
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk
Poland	NIO-PIB Oddzial w Gliwicach	Gliwice
Poland	Centrum Badan klinicznych Jagiellonskie Centrum Innowacji	Kraków
Poland	Siedleckie Centrum Onkologii	Olsztyn
Poland	Uniwersytecki Szpital	Poznan
Poland	NIO-PIB Klinika Gine-Onk	Warsaw
Poland	Lower Silesian Oncology, Pulmonology and Hematology Center, Department of Oncological Gynecology	Wroclaw
Romania	Bucharest CF2 Hospital	Bucharest
Romania	Ovidius Clinical Hospital SRL	Constanta
Romania	Onco Clinic Consult S.A.	Craiova
Romania	Oncology Center "Sf. Nectarie"	Craiova
Romania	Gral Medical S.R.L. - Oncofort Hospital	Pitesti
Romania	Oncocenter, Oncology Clinic SRL	Timisoara
Romania	SC Oncomed SRL	Timisoara
Slovenia	Institute of Oncology Ljubljana	Ljubljana
Slovenia	University Clinical Center Maribor	Maribor
Spain	CHUAC (Hospital de Coruña)	A Coruna
Spain	Hospital del Mar	Barcelona
Spain	Hospital Galdakao-Usansolo	Galdakao
Spain	Hospital Universitario de Jaen	Jaen
Spain	H.G.U. Jerez de la Frontera	Jerez de la Frontera
Spain	Hospital U Insular de GC	Las Palmas
Spain	Hospital de Leon	Leon
Spain	HCU Santiago de Compostela	Santiago de Compostela
Spain	Hospital Universitario de Valme	Seville
Sweden	Linkoping University Hospital	Linköping
Sweden	Karolinska University Hospital	Stockholm
United States	Northside Hospital	Atlanta	Georgia
United States	Texas Oncology-Austin Central	Austin	Texas
United States	OhioHealth Institute	Columbus	Ohio
United States	Oncology Associates of Oregon	Eugene	Oregon
United States	Parkview Research Center	Fort Wayne	Indiana
United States	Texas Oncology-Fort Worth Cancer Center	Fort Worth	Texas
United States	Dr. Sudarshan K. Sharma, Ltd.	Hinsdale	Illinois
United States	Indiana University	Indianapolis	Indiana
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota
United States	FirstHealth Carolinas	Pinehurst	North Carolina
United States	Northwest Cancer Specialists	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Texas Oncology-San Antonio Medical Center	San Antonio	Texas
United States	St. Joseph	Savannah	Georgia
United States	Maryland Oncology Hematology, P.A.	Silver Spring	Maryland
United States	Oklahoma Cancer Specialists and Research Institute	Tulsa	Oklahoma
United States	Kaiser Permanente Center	Vallejo	California
United States	Good Samaritan Hospital Medical Center	West Islip	New York

Sponsors (3)

Lead Sponsor	Collaborator
Kartos Therapeutics, Inc.	European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation

Countries where clinical trial is conducted

United States,  Austria,  Canada,  Denmark,  Estonia,  Finland,  Georgia,  Hungary,  Israel,  Italy,  Lithuania,  Norway,  Poland,  Romania,  Slovenia,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: To determine the navtemadlin Phase 3 dose	Safety review committee (SRC) will determine the navtemadlin Phase 3 dose for Part 2 based on safety data from Part 1	12 months
Primary	Part 2: To compare progression-free (PFS) survival by independent review committee (IRC) between navtemadlin and placebo	PFS defined as the time from randomization to disease progression by IRC or death, whichever occurs first	50 months
Secondary	Part 1: To evaluate the treatment effect of navtemadlin on PFS by IRC and investigator assessment	PFS defined as the time from randomization to disease progression by IRC/investigator assessment or death, whichever occurs first	50 months
Secondary	Part 2: To evaluate the treatment effect of navtemadlin on the time to first subsequent treatment (TFST)	TFST defined as the time from randomization to initiation of first subsequent anticancer therapy or death, whichever occurs first	50 months
Secondary	Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin	Will determine the Maximum observed concentration (Cmax)	1 day
Secondary	Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin	Will determine the area under the plasma concentration versus time curve (AUC)	1 day
Secondary	Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin	Will determine the time of maximum plasma concentration (Tmax)	1 day
Secondary	Parts 1 and 2: To evaluate the treatment effect of navtemadlin on the disease control rate (DCR)	Best response of complete response (CR), partial response (PR) or stable disease (SD) by IRC/investigator assessment among subjects with PR as best response from prior chemotherapy	50 months