Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS Mutant Non-Small Cell Lung Cancer

NCT04735068 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: UPCC 21520844511
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate using hydroxychloroquine (HCQ) along with binimetinib as an effective method for treating cancer. All patients will receive binimetinib at a standard dose approved for other cancers. The dose of HCQ will also be fixed based on ongoing phase I studies. Eligible subjects will have lung cancer that has a mutation in a key cancer gene called KRAS, and the cancer has spread to other parts of their body.

Conditions

Non-Small Cell Lung Cancer; KRAS Mutation-Related Tumors

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

  16 months

• Number of Patients With Adverse Events

  as assessed by CTCAE v5.0

  16 months

Secondary Outcomes (2)

• Progression-free Survival (PFS)

  16 months

• Overall Survival (OS)

  16 months

Study Arms (1)

Binimetinib and Hydroxychloroquine

EXPERIMENTAL

Hydroxychloroquine (HCQ)in combination with Binimetinib (B). The starting dose for HCQ will be 400mg. Tablets of HCQ are available in 200 mg strength. HCQ will be administered in divided doses (every 12 hours) with or without food. The starting dose of B is 45mg. B will be administered in divided doses (every 12 hours) with or without food

Drug: Binimetinib Pill; Drug: Hydroxychloroquine Pill

Interventions

Binimetinib Pill DRUG

Patients will be treated with B 45 mg two times daily and HCQ 400 mg twice daily beginning on day 1. The dose of HCQ is based on an ongoing Phase 1 trial, and may be modified in a future amendment prior to the first patient enrolled. Efforts will be made to ensure dose homogeneity throughout the trial. Treatment will be administered on an outpatient basis on a 28 day cycle

Binimetinib and Hydroxychloroquine

Hydroxychloroquine Pill DRUG

Patients will be treated with B 45 mg two times daily and HCQ 400 mg twice daily beginning on day 1. The dose of HCQ is based on an ongoing Phase 1 trial, and may be modified in a future amendment prior to the first patient enrolled. Efforts will be made to ensure dose homogeneity throughout the trial. Treatment will be administered on an outpatient basis on a 28 day cycle

Binimetinib and Hydroxychloroquine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Metastatic or incurable NSCLC
• Presence of a non-synonymous mutation in KRAS
• Patient must have received at least one prior systemic therapy for metastatic NSCLC or be intolerant/ineligible/refuse available therapies with known benefit
• Ability and willingness to sign a written informed consent document
• Age ≥18 years old
• At least one measureable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• ECOG performance status 0-1
• Adequate organ function
• Women of childbearing potential must have a negative serum pregnancy test performed within 72hours of the first dose of study therapy. Subjects of reproductive potential must agree to use acceptable birth control methods (see Appendix B for childbearing potential).
• Qtc \< 500 mSec on EKG
• Must be able to swallow tablets
• Must be willing to comply with protocol procedures (including completion of diaries and outcome measures

You may not qualify if:

• Currently participating in or has participated in a study of an investigational agent or anticipated use of an investigational device within 4 weeks of the first dose of study treatment.
• Untreated symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Prior monoclonal antibody within 4 weeks prior to enrollment, or individuals who have not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, non-invasive bladder tumors, or in situ cervical cancer
• Active infection requiring systemic therapy with IV antibiotics
• History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Known psychiatric or substance abuse disorders as documented in the chart that, in the opinion of the investigator, would interfere with cooperation with the requirements of the trial.
• Pregnant or breastfeeding women
• Anticipated receipt of any live vaccine within 30 days prior to the first dose of trial treatment.
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).
• Patients receiving cytochrome P450 enzyme-inducing anticonvulsant drugs (EIADs) (i.e.
• phenytoin, carbamazepine, Phenobarbital, primidone or oxcarbazepine) within 4 weeks of the start of the study treatment
• Known Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and/or HCV will be permitted)
• Patients with a previously documented retinal vein occlusion.
• History or evidence of increased cardiovascular risk including any of the following:

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead
• Pfizer: collaborator

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (1)

• Aggarwal C, Maity AP, Bauml JM, Long Q, Aleman T, Ciunci C, D'Avella C, Volpe M, Anderson E, Jones LM, Sun L, Singh AP, Marmarelis ME, Cohen RB, Langer CJ, Amaravadi R. A Phase II Open-Label Trial of Binimetinib and Hydroxychloroquine in Patients With Advanced KRAS-Mutant Non-Small Cell Lung Cancer. Oncologist. 2023 Jul 5;28(7):644-e564. doi: 10.1093/oncolo/oyad106.

  PMID: 37186063 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

binimetinib; Hydroxychloroquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chloroquine; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Melissa Volpe
• Organization: University of Pennsylvania

melissa.volpe@Pennmedicine.upenn.edu

215-220-9703

Study Officials

• Charu Aggarwal, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2021
• First Posted: February 2, 2021
• Study Start: April 9, 2021
• Primary Completion: August 21, 2022
• Study Completion: December 31, 2023
• Last Updated: April 1, 2025
• Results First Posted: April 1, 2025

Record last verified: 2025-03

Locations

US (1)