Sponsor Decision

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.

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