Phase 2 Study of AUY922 in NSCLC Patients With Exon 20 Insertion Mutations in EGFR

NCT01854034 | Completed Phase 2 Results DMC

• 1 other identifier: 12-484
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific cancer. "Investigational" means that the drug is being studied. It also means that the FDA has not yet approved the drug for your type of cancer or for any use outside of research studies. It has been found that some people with NSCLC have a change (mutation) in a certain gene called the EGFR gene. This mutated gene helps cancer cells grow. The majority of NSCLC patients with EGFR mutations achieve good outcomes with erlotinib or other EGFR inhibitor therapies, with a high response rate, prolonged progression-free survival and possibly improved overall survival from therapy. However, the 4% of EGFR mutant patients that harbor an exon 20 insertion mutation historically have reaped little benefit from EGFR-directed therapy due to the low affinity of this mutation for direct EGFR inhibitors, especially erlotinib and gefitinib (see Yasuda et al, Lancet Oncol 2011). This group of patients is ideal for studying other targeted therapeutic strategies that could affect the oncogene mutation in EGFR via alternative mechanisms. AUY922 is an investigational drug that may stop cancer cells from growing abnormally. This drug has been used in other research studies. Information from those other research studies suggests that AUY922 may be effective in killing cancer cells in patients with exon 20 insertion mutations in EGFR. The purpose of this study is to test the safety of AUY922 and determine how well AUY922 works for participants with advanced NSCLC and exon 20 insertion mutations in EGFR.

Conditions

Non Small Cell Lung Cancer

Keywords

Advanced disease; EGFR mutation

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  The number of participants that achieved a response to treatment as assessed by Response Evaluation Criteria is Solid Tumors (RECIST). Response is defined as having achieved either a complete response (CR) or a partial response (PR). * Complete Response (CR): Disappearance of all target lesions. Any pathological lymph node must have reduction in short axis to \< 10 mm. * Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

  From the start of treatment until the time of disease progression, median duration of follow-up of about 3 months

Secondary Outcomes (3)

• Median Progression Free and Overall Survival

  From the start of treatment until the time or death or disease progression

• The Number of Participants With Treatment Related Serious Adverse Events

  From the start of treatment until 28 days after the end of treatment

• Exon 20 EGFR Mutations Among Participants That Responded to Treatment

  Baseline, at the time of response

Study Arms (1)

AUY922 Treatment Arm

EXPERIMENTAL

AUY922 administered once weekly via intravenous, 70 mg/m2

Drug: AUY922

Interventions

AUY922 DRUG

AUY922 administered intravenously once a week at 70mg/m2

AUY922 Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed stage IV or recurrent NSCLC
• Measurable disease by RECIST 1.0
• Must have received at least one prior line of therapy for advanced lung cancer (no maximum number)
• Life expectancy of at least 12 weeks

You may not qualify if:

• Pregnant or breastfeeding
• Radiation within 2 weeks
• Cytotoxic chemotherapy or monoclonal antibodies within 4 weeks
• EGFR tyrosine kinase inhibitor within 2 weeks
• Other small molecule inhibitor within 2 weeks
• Experimental treatment within 30 days
• Prior treatment with any HSP90 or HDAC inhibitor compound
• Known and untreated brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AUY922
• Unresolved diarrhea greater than or equal to CTCAE version 4, grade 1
• Major surgery within 2 weeks of starting study drug or have not recovered from side effects of surgery
• Known disorders due to a deficiency in bilirubin glucuronidation
• Requiring use of therapeutic doses of warfarin (Coumadin)
• History of long QT syndrome
• History of clinically manifest ischemic heart disease, heart failure or left ventricular dysfunction

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (4)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• Piotrowska Z, Costa DB, Oxnard GR, Huberman M, Gainor JF, Lennes IT, Muzikansky A, Shaw AT, Azzoli CG, Heist RS, Sequist LV. Activity of the Hsp90 inhibitor luminespib among non-small-cell lung cancers harboring EGFR exon 20 insertions. Ann Oncol. 2018 Oct 1;29(10):2092-2097. doi: 10.1093/annonc/mdy336.

  PMID: 30351341 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

5-(2,4-dihydroxy-5-isopropylphenyl)-4-(4-morpholin-4-ylmethylphenyl)isoxazole-3-carboxylic acid ethylamide

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Lecia Van Dam Sequist, M.D.
• Organization: Massachusetts General Hospital

lvsequist@partners.org

617-724-4000

Study Officials

• Lecia Sequist, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 12, 2013
• First Posted: May 15, 2013
• Study Start: July 1, 2013
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: April 10, 2018
• Results First Posted: April 10, 2018

Record last verified: 2018-03

Locations

US (4)