Study on Defactinib, Avutometinib, and Nivolumab for Treating Advanced Non-Small Cell Lung Cancer with LKB1 Mutation

Sponsor: Emory University

Sponsor score: 40
Inactive

ClinicalTrials ID:NCT06495125

Provider View

This clinical trial is exploring a new treatment combination for patients with advanced non-small cell lung cancer that has a specific LKB1 mutation and has not responded to previous anti-PD1 treatments. The study aims to see if combining the drugs defactinib, avutometinib, and nivolumab can help control the cancer.

Patient Parameters

Program Overview

This phase II study is testing how well a combination of drugs—defactinib, avutometinib, and nivolumab—works in treating patients with advanced non-small cell lung cancer (NSCLC) that has a specific LKB1 mutation and has not responded to previous anti-PD1 treatments. Defactinib and avutometinib are kinase inhibitors that target proteins in tumor cells, potentially slowing or stopping their growth. Nivolumab is an immunotherapy drug that may help the immune system attack cancer cells. The study aims to determine if this combination can effectively kill more cancer cells in these patients.

Description

Primary Objective:

  • To find out how effective the combination of defactinib, avutometinib, and nivolumab is in keeping the cancer from getting worse for at least six months in patients with LKB1-mutated lung adenocarcinoma.

Secondary Objective:

  • To evaluate how well the cancer responds to the treatment, how long patients live overall, and to assess any side effects.

Tertiary/Exploratory Objective:

  • To study biomarkers in tumor samples collected before and during the study from some patients.

Study Outline:

  • Patients will take defactinib by mouth twice a day for 21 days, avutometinib by mouth twice a week, and receive nivolumab through an IV on the first day of each cycle. Each cycle lasts 28 days and will continue unless the cancer progresses or side effects become unacceptable.
  • Patients will also have biopsies, blood tests, and imaging scans like CT or PET during the study.
  • After finishing the treatment, patients will have follow-up visits every three months for up to five years.

Eligibility Criteria

Inclusion Criteria

  • Diagnosed with non-small cell lung cancer, specifically lung adenocarcinoma.
  • Have advanced cancer that cannot be treated with surgery or combined therapies.
  • Have a known LKB1 mutation.
  • For Cohort A: Must also have a KRAS mutation.
  • Cancer must have progressed after previous treatment with an immune checkpoint inhibitor and first-line chemotherapy.
  • Must have measurable cancer that can be tracked with scans.
  • Age 18 or older.
  • Good overall health with an ECOG performance status of 0 or 1.
  • Must have recovered from previous treatment side effects to a certain level.
  • Must meet specific blood count and organ function criteria.
  • Must be able to take oral medications.
  • Must agree to use effective birth control during and after the study.
  • Must be able to understand and sign a consent form.
  • Must have a specific heart rhythm measurement within normal limits.

Exclusion Criteria

  • Have had other cancer treatments within the last three weeks or have not recovered from side effects of previous treatments.
  • Currently taking other experimental drugs.
  • Have unstable or symptomatic brain metastases.
  • Have a history of autoimmune conditions that could worsen with nivolumab.
  • Have had severe autoimmune reactions to previous treatments.
  • Have allergies to similar drugs as those in the study.
  • Have uncontrolled illnesses or infections.
  • Have active hepatitis B, C, or HIV.
  • Have active skin disorders needing systemic treatment in the past year.
  • Have certain eye conditions or disorders.
  • Cannot swallow pills or have digestive issues affecting absorption.
  • Taking warfarin or certain other medications that interact with study drugs.
  • Have a treatable mutation with an FDA-approved therapy, except for KRAS.
  • Have had another cancer within the last two years, except for certain low-risk cancers.
  • Are pregnant or breastfeeding.

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