A Clinical Study on the Safety and Efficacy of Debio 0932 in Combination With Standard of Care in Patients With Non-small Cell Lung Cancer [NSCLC]

Study Overview
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Brief Summary
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Part A of this study will investigate the Maximum Tolerated Dose of Debio 0932 in combination with standard of care chemotherapy for the first- and second-line treatment of advanced NSCLC.

Detailed Description
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Part A of this study will determine the Maximum Tolerated Dose of Debio 0932 in combination with cisplatin/pemetrexed and cisplatin/gemcitabine in treatment-naïve patients with Stage IIIb or IV NSCLC, and with docetaxel in previously treated patients with Stage IIIb or IV NSCLC. Escalating doses of Debio 0932 will be given to subsequent patients in combination with standard doses of these 3 background chemotherapies.

Official Title
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A Phase I-II Evaluation of the Safety and Efficacy of the Oral HSP90 Inhibitor Debio 0932 in Combination With Standard of Care in first-and Second-line Therapy of Patients With Stage IIIb or IV Non-small Cell Lung Cancer-the HALO Study (HSP90 Inhibition And Lung Cancer Outcomes)

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Debio 0932
* Drug: Cisplatin
* Drug: Pemetrexed
* Drug: Gemcitabine
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of NSCLC with confirmed squamous or non-squamous tumour histology, without known epidermal growth factor receptor (EGFR) mutation Advanced or metastatic disease (Stage IIIb or IV) Patients to be treated with cisplatin/gemcitabine or cisplatin/pemetrexed: No previous systemic treatment with chemotherapy, targeted therapy or investigational agents (except adjuvant therapy if > 6 months ago); Patients to be treated with docetaxel: ≥ 1 previous treatment with chemotherapy Measurable disease by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria ECOG performance score 0-1 Life expectancy ≥ 3 months Adequate bone marrow-, renal- and hepatic function LVEF ≥ 55% on cardiac ultrasound Exclusion Criteria: Symptomatic brain metastases Gastro-intestinal disorders that could affect drug absorption (including, but not limited to, major abdominal surgery, significant bowel obstruction, ulcerative colitis, Crohn's disease) Concurrent treatment with any other systemic anti-cancer therapy Serious concomitant uncontrolled medical conditions

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cisplatin, Pemetrexed, Debio 0932<br>Cisplatin, Pemetrexed, Debio 0932 | Drug: Debio 0932<br>* Debio 0932 will be administered as daily oral tablets at a starting dose of 250 mg four times per day (QD).<br>Drug: Cisplatin<br>* Cisplatin 75 mg/m2 body surface area (BSA) will be administered on Day 1 of each 21-day treatment cycle.<br>Drug: Pemetrexed<br>* Pemetrexed 500 mg/m2 BSA will be administered on Day 1 of each 21 day treatment cycle.<br>|
| Experimental: Cisplatin, Gemcitabine, Debio 0932<br>Cisplatin, Gemcitabine, Debio 0932 | Drug: Debio 0932<br>* Debio 0932 will be administered as daily oral tablets at a starting dose of 250 mg four times per day (QD).<br>Drug: Cisplatin<br>* Cisplatin 75 mg/m2 body surface area (BSA) will be administered on Day 1 of each 21-day treatment cycle.<br>Drug: Gemcitabine<br>* Gemcitabine 1250 mg/m2 BSA will be administered on Days 1 and 8 of each 21-day treatment cycle.<br>|
| Experimental: Docetaxel, Debio 0932<br>Docetaxel, Debio 0932 | Drug: Debio 0932<br>* Debio 0932 will be administered as daily oral tablets at a starting dose of 250 mg four times per day (QD).<br>Drug: Docetaxel<br>* Docetaxel 60 or 75 mg/m2 BSA will be administered on Day 1 of each 21-day treatment cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of Dose Limiting Toxicities |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in vital signs and Eastern Cooperative Oncology Group Performance Status (ECOG PS) |  | Day 1 of each treatment cycle until disease progression or study drug toxicity | 
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Every treatment cycle until disease progression or study drug toxicity | 
| Incidence of laboratory abnormalities |  | 2 to 4 times every treatment cycle until disease progression or study drug toxicity | 
| Incidence of treatment discontinuations due to AEs and SAEs |  | Every treatment cycle until diseases progression or study drug toxicity | 
| Change in left ventricular ejection fraction (LVEF) |  | Baseline and after 4 weeks of treatment | 
| Pharmacokinetic parameters of Debio 0932 and its metabolite Debio 0932-MET1 |  | 22 days | 
| Pharmacokinetic parameters of cisplatin/pemetrexed, cisplatin/gemcitabine, and docetaxel |  | 22 days | 
| Best overall tumor response |  | 22 days | 
| Pharmacodynamic biomarkers |  | 22 days | 
| Pharmacogenomic, tumour pharmacogenetic, proteomic, and pharmacogenetic factors predictive of response to Debio 0932 |  | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Efficacy, HSP90, Debio 0932, Standard of care treatment, NSCLC