Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Pembrolizumab

Immunomodulating Agents

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Navtemadlin will be administered orally, once daily (QD), on days 1-7 in a 21-day cycle.

Pembrolizumab will be administered intravenously on Day 1 of a 21-day cycle.

Navtemadlin placebo will be administered orally, once daily (QD), on days 1-7 in a 21-day cycle.

Pembrolizumab will be administered intravenously on Day 1 of a 21-day cycle.

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

Navtemadlin

Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth.

Navtemadlin Placebo

Pembrolizumab is a humanized antibody used in cancer immunotherapy that will be administered intravenously

This study evaluates Navtemadlin (KRT-232) in combination with Pembrolizumab as a maintenance therapy in patients with locally advanced and metastatic non small cell lung cancer.

This is a 2 part, phase 1b/2, maintenance study for patients who have achieved a partial response (PR) or complete response (CR) after completion of up to 4 cycles of a combination platinum-based chemotherapy plus CPI regimen.

Phase 1b is a 3+3 dose escalation design that will be used to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) of navtemadlin in combination with pembrolizumab. A Safety Review Committee (SRC) will review the safety data during the dose escalation to decide on dose escalation and/or exploration of intermediate doses.

Phase 2 will evaluate the efficacy and safety of the RP2D of navtemadlin plus pembrolizumab compared to navtemadlin placebo plus pembrolizumab. Each Arm will have approximately 40 subjects enrolled for a total of approximately 80 subjects. Eligible subjects will be randomized 1:1. This part of the study has a randomized, controlled, double-blind design. A stratified, permuted-block randomization scheme will be used for treatment allocation.

Study of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Locally Advanced and Metastatic Non-Small Cell Lung Cancer

A Two-Part, Phase 1b/2, Multicenter, Open-Label, Dose Escalation and Double-Blind, Randomized, Placebo-Controlled, Dose Expansion Study of the Safety, Efficacy and Pharmacokinetics of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Subjects With Locally Advanced and Metastatic Non-Small Cell Lung Cancer

The Safety Review Committee will determine the RP2D based on safety data of the combination of navtemadlin and pembrolizumab.

PFS is defined as the time from randomization date to disease progression (assessed by the Independent Review Committee \[IRC\] per RECIST v1.1) or death, whichever occurs first

Will determine the Maximum observed concentration (Cmax) on Cycle 1 Day 1

Will determine the area under the plasma concentration versus time curve (AUC) on Cycle 1 Day 1

Will determine the time of maximum plasma concentration (Tmax) on Cycle 1 Day 1

PFS is defined as the time from first dose date to disease progression (assessed by the IRC and Investigator per RECIST v1.1) or death, whichever occurs first

PFS is defined as the time from randomization date to disease progression (assessed by the Investigator per RECIST v1.1) or death, whichever occurs first

Kartos Therapeutics, Inc.

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Endometrial Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

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

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

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

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

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

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

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

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth

Navtemadlin placebo is a placebo that is the same in appearance to navtemadlin drug taken by mouth

John Mei

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.

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

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

Safety review committee (SRC) will determine the navtemadlin Phase 3 dose for Part 2 based on safety data from Part 1

PFS defined as the time from randomization to disease progression by IRC or death, whichever occurs first

PFS defined as the time from randomization to disease progression by IRC/investigator assessment or death, whichever occurs first

TFST defined as the time from randomization to initiation of first subsequent anticancer therapy or death, whichever occurs first

Will determine the Maximum observed concentration (Cmax)

Will determine the area under the plasma concentration versus time curve (AUC)

Will determine the time of maximum plasma concentration (Tmax)

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Study of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Locally Advanced and Metastatic Non-Small Cell Lung Cancer	NCT05705466	Non Small Cell ...	Navtemadlin Navtemadlin Pla... Pembrolizumab	18 Years -	Kartos Therapeutics, Inc.
Study of Navtemadlin as Maintenance Therapy in TP53WT Advanced or Recurrent Endometrial Cancer	NCT05797831	Endometrial Can...	Navtemadlin Navtemadlin Pla...	18 Years -	Kartos Therapeutics, Inc.

Spots Global Cancer Trial Database for navtemadlin placebo