Clinical trial NCT05705466: Study of Navtemadlin Plus Pembrolizumab as Maintenance Therapy in Locally Advanced and Metastatic Non-Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: Navtemadlin
Lead sponsor: Kartos Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-30
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Phase 1b- To determine the recommended Phase 2 dose (RP2D)
timeFrame: 21 days
measure: Phase 2- To assess the treatment effect of navtemadlin plus pembrolizumab treatment on PFS compared with the treatment effect of navtemadlin placebo plus pembrolizumab treatment.
timeFrame: 64 Months
Secondary outcomes:
measure: Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
timeFrame: 1 day
measure: Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
timeFrame: 1 day
measure: Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin
timeFrame: 1 day
measure: Phase 1b- To assess the treatment effect on progression-free survival (PFS)
timeFrame: 64 Months
measure: Phase 2- To assess the treatment effect of navtemadlin plus pembrolizumab treatment on PFS compared with the treatment effect of navtemadlin placebo plus pembrolizumab treatment.
timeFrame: 64 Months
Other outcomes:
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