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

• ClinicalTrials.gov Identifier: NCT05797831
• Recruitment Status: Recruiting
• First Posted: April 4, 2023
• Last Update Posted: May 2, 2024
• Sponsor: Kartos Therapeutics, Inc.
• Collaborators: European Network of Gynaecological Oncological Trial Groups (ENGOT); GOG Foundation
• Information provided by (Responsible Party): Kartos Therapeutics, Inc.

Tracking Information

• First Submitted Date: March 7, 2023
• First Posted Date: April 4, 2023
• Last Update Posted Date: May 2, 2024
• Actual Study Start Date: July 17, 2023
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 21, 2023)

• Part 1: To determine the navtemadlin Phase 3 dose [ Time Frame: 12 months ]
  Safety review committee (SRC) will determine the navtemadlin Phase 3 dose for Part 2 based on safety data from Part 1
• Part 2: To compare progression-free (PFS) survival by independent review committee (IRC) between navtemadlin and placebo [ Time Frame: 50 months ]
  PFS defined as the time from randomization to disease progression by IRC or death, whichever occurs first

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 21, 2023)

• Part 1: To evaluate the treatment effect of navtemadlin on PFS by IRC and investigator assessment [ Time Frame: 50 months ]
  PFS defined as the time from randomization to disease progression by IRC/investigator assessment or death, whichever occurs first
• Part 2: To evaluate the treatment effect of navtemadlin on the time to first subsequent treatment (TFST) [ Time Frame: 50 months ]
  TFST defined as the time from randomization to initiation of first subsequent anticancer therapy or death, whichever occurs first
• Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin [ Time Frame: 1 day ]
  Will determine the Maximum observed concentration (Cmax)
• Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin [ Time Frame: 1 day ]
  Will determine the area under the plasma concentration versus time curve (AUC)
• Parts 1 and 2: To determine the pharmacokinetic (PK) profile of navtemadlin [ Time Frame: 1 day ]
  Will determine the time of maximum plasma concentration (Tmax)
• Parts 1 and 2: To evaluate the treatment effect of navtemadlin on the disease control rate (DCR) [ Time Frame: 50 months ]
  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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer
• 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

Brief 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Endometrial Cancer

Intervention

• Drug: Navtemadlin
  Navtemadlin is an experimental MDM2 anticancer drug taken by mouth
  Other Name: KRT-232
• Drug: Navtemadlin Placebo
  Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth

Study Arms

• Experimental: Part 1 Arm 1
  Navtemadlin administered orally at 180 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.
  Intervention: Drug: Navtemadlin
• Experimental: Part 1 Arm 2
  Navtemadlin administered orally at 240 mg, once daily (QD) on Days 1-7 in a 28-day treatment cycles.
  Intervention: Drug: Navtemadlin
• No Intervention: Part 1 Arm 3
  Observational control ("watch and wait") on a 28-day cycle.
• Experimental: Part 2 Arm A
  Navtemadlin administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.
  Intervention: Drug: Navtemadlin
• Experimental: Part 2 Arm B
  Navtemadlin administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day treatment cycles.
  Intervention: Drug: Navtemadlin
• Placebo Comparator: Part 2 Arm C
  Placebo administered orally at 180 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.
  Intervention: Drug: Navtemadlin Placebo
• Placebo Comparator: Part 2 Arm D
  Placebo administered orally at 240 mg once daily (QD) on Days 1-7 in a 28-day administration cycle.
  Intervention: Drug: Navtemadlin Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 21, 2023): 268
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2027
• Estimated Primary Completion Date: August 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: John Mei; 650-542-0136; jmei@kartosthera.com

• Listed Location Countries: Austria, Canada, Denmark, Estonia, Finland, Georgia, Hungary, Israel, Italy, Lithuania, Norway, Poland, Romania, Slovenia, Spain, Sweden, United States

Administrative Information

• NCT Number: NCT05797831
• Other Study ID Numbers: KRT-232-118; ENGOT en-21 ( Other Identifier: ENGOT ); GOG-3089 ( Other Identifier: GOG Foundation )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Kartos Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Kartos Therapeutics, Inc.
• Original Study Sponsor: Same as current

Collaborators

• European Network of Gynaecological Oncological Trial Groups (ENGOT)
• GOG Foundation

• Investigators: Not Provided
• PRS Account: Kartos Therapeutics, Inc.
• Verification Date: April 2024