Phase 1b/2 Study of Retaspimycin HCl (IPI-504) in Combination With Everolimus in KRAS Mutant Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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Study IPI-504-15 is a Phase 1b/2 clinical trial to evaluate the safety and efficacy of retaspimycin HCl (IPI-504) plus everolimus in patients with KRAS mutant Non-small Cell Lung Cancer (NSCLC).

Detailed Description
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This is a Phase Ib/2 study of retaspimycin HCl (IPI-504) in combination with everolimus. The Phase 1b portion is to test the safety and tolerability of retaspimycin HCl (IPI-504) in combination with everolimus and determine the highest dose of retaspimycin HCl (IPI-504) and everolimus that can safely be given in combination. The Phase 2 portion of this study will continue the evaluation of safety of retaspimycin HCl (IPI-504) in combination with everolimus and compare the effect of the study drugs on tumor response and life expectancy in patients with KRAS mutant NSCLC.

Official Title
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A Phase 1b/2 Study of Retaspimycin HCl (IPI-504) in Combination With Everolimus in Patients With KRAS Mutant NSCLC

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: IPI-504
* Drug: Everolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age Voluntarily sign an informed consent form (ICF). Pathological diagnosis of KRAS mutation positive NSCLC - Stage IIIB or IV Archival NSCLC tissue available to provide for analysis or have a lesion that is accessible for biopsy Experienced disease progression during or after receiving at least 1 prior platinum-containing chemotherapy regimen. ECOG performance of 0-1. Exclusion Criteria: Prior treatment with IPI-504 or other Hsp90 inhibitors. Prior treatment with everolimus, other rapamycin analogs, AP23573(Ridaforolimus), rapamycin, or other mTOR inhibitors. Has not recovered from any toxicities related to prior treatment (to Grade 1 or baseline), excluding alopecia. Inadequate hematologic function defined as: Inadequate hepatic function defined by: Inadequate renal function defined by serum creatinine >1.5 x ULN.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Retaspimycin HCl (IPI-504) and Everolimus<br>Retaspimycin HCl (IPI-504) and everolimus will be administered on a 21-day cycle. All patients will remain on study until progression of disease or intolerability to study treatments occurs. | Drug: IPI-504<br> <br> * Other names: retaspimycin hydrochloride;Drug: Everolimus<br> <br> * Other names: Afinitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Overall response rate (ORR), defined as a partial response (PR) or complete response (CR) occurring at any point post-treatment according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). | Up to three years from last patient study visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Progression free survival (PFS), defined as time from study entry to progression or death whichever occurs first. | Up to three years from last patient study visit | 
| Time to Progression | Time to progression (TTP), defined as time from study entry to progression. | Up to three years from last patient study visit | 
| Overall Survival | Overall survival (OS), defined as time from study entry to death due to any cause, in patients with KRAS mutant NSCLC administered IPI-504 plus everolimus. | Up to three years from last patient study visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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KRAS mutant, Non-Small Cell Lung Cancer, NSCLC