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

NCT ID: NCT05705466

Last Updated: 2024-03-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-30
• Study Completion Date: 2027-06-30

Brief Summary

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.

Detailed Description

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.

Conditions

Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Navtemadlin in combination with pembrolizumab

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.

Group Type: EXPERIMENTAL

Navtemadlin

Intervention Type: DRUG

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

Pembrolizumab

Intervention Type: DRUG

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

Navtemadlin placebo in combination with pembrolizumab

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.

Group Type: PLACEBO_COMPARATOR

Navtemadlin Placebo

Intervention Type: DRUG

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

Pembrolizumab

Intervention Type: DRUG

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

Interventions

Navtemadlin

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

Intervention Type: DRUG

Navtemadlin Placebo

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

Intervention Type: DRUG

Pembrolizumab

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

Intervention Type: DRUG

Other Intervention Names

KRT-232; Keytruda

Eligibility Criteria

Inclusion Criteria

• ECOG 0-1
• Histologically or cytologically confirmed diagnosis of NSCLC documented as TP53WT
• Locally advanced or metastatic disease; must have completed up to 4 cycles of platinum-based chemo plus CPI and achieved a CR or PR per RECIST V1.1
• Adequate hematologic, hepatic and renal function (within 14 days)

Exclusion Criteria

• Symptomatic or uncontrolled central nervous system (CNS) metastases
• Prior treatment with a MDM2 inhibitor
• Grade 2 or higher QTc prolongation (>480 msec per NCI-CTCAE criteria version 5.0)
• History of bleeding diathesis; major hemorrhage or intracranial hemorrhage within 24 weeks
• History of major organ transplant
• Active pneumonitis or known history of interstitial lung disease, drug-related pneumonitis, or radiation pneumonitis
• Prior radiotherapy, cytoreductive therapy, cytokine therapy or any investigational therapy within 28 days
• Medical condition, serious intercurrent illness, psychiatric condition or other circumstance that, in the Investigator's judgment could jeopardize the subject's safety, or that could interfere with study objectives

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kartos Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

KRT-232-119

Identifier Type: -

Identifier Source: org_study_id