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

NCT05705466 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: KRT-232-119
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Non Small Cell Lung Cancer

Keywords

Navtemadlin

Outcome Measures

Primary Outcomes (2)

• Phase 1b- To determine the recommended Phase 2 dose (RP2D)

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

  21 days

• 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.

  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

  64 Months

Secondary Outcomes (5)

• Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin

  1 day

• Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin

  1 day

• Phase 1b- To characterize the pharmacokinetic (PK) profile of navtemadlin

  1 day

• Phase 1b- To assess the treatment effect on progression-free survival (PFS)

  64 Months

• 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.

  64 Months

Study Arms (2)

Navtemadlin in combination with pembrolizumab

EXPERIMENTAL

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.

Drug: Navtemadlin; Drug: Pembrolizumab

Navtemadlin placebo in combination with pembrolizumab

PLACEBO COMPARATOR

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.

Drug: Navtemadlin Placebo; Drug: Pembrolizumab

Interventions

Navtemadlin DRUG

Navtemadlin is an experimental MDM2 anticancer drug taken by mouth.

Also known as: KRT-232

Navtemadlin in combination with pembrolizumab

Navtemadlin Placebo DRUG

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

Navtemadlin placebo in combination with pembrolizumab

Pembrolizumab DRUG

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

Also known as: Keytruda

Navtemadlin in combination with pembrolizumab; Navtemadlin placebo in combination with pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Kartos Therapeutics, Inc.: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

navtemadlin; 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(isopropylsulfonyl)-3-methylbutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: January 30, 2023
• Study Start: June 1, 2023
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: March 22, 2024

Record last verified: 2024-03