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

Kartos Therapeutics

Status and phase: Withdrawn; Phase 2; Phase 1

Conditions: Non Small Cell Lung Cancer

Treatments: Drug: Navtemadlin; Drug: Navtemadlin Placebo; Drug: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05705466

KRT-232-119

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

Navtemadlin in combination with pembrolizumab

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Navtemadlin

Navtemadlin placebo in combination with pembrolizumab

Placebo Comparator group

Description:

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.

Treatment:

Drug: Navtemadlin Placebo

Drug: Pembrolizumab