Non-small Cell Lung Cancer MedDRA version: 16.1 Level: LLT Classification code 10025054 Term: Lung cancer non-small cell stage IIIB System Organ Class: 100000004864 MedDRA version: 16.1 Level: LLT Classification code 10025055 Term: Lung cancer non-small cell stage IV System Organ Class: 100000004864
Conditions
Interventions
Product Name: Debio 0932, 100mg tablet
Product Code: Debio 0932
Pharmaceutical Form: Tablet
Current Sponsor code: Debio 0932
Other descriptive name: Debio 0932
Concentration unit: mg milligram(s)
Conc
Sponsors
Debiopharm International SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Part A : 1. Age = 18 years; 2. Diagnosis of NSCLC with confirmed squamous or non-squamous tumour histology, without known EGFR mutation; 3. Archived tumour sample available; 4. Advanced or metastatic disease (Stage IIIb or IV) ; 5. 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. 6. Candidate for treatment with cisplatin/pemetrexed or cisplatin/gemcitabine or docetaxel as determined by the Investigator; 7. Measurable disease by the RECIST criteria; 8. ECOG performance score 0 - 1; 9. Life expectancy = 3 months; 10. ANC = 1 500/µL; 11. Platelets = 100 000/µL; 12. Creatinine clearance = 60 mL/minutes (Cockroft – Gault formula); 13. AST and ALT = 2.5 x ULN; in case of documented liver metastases, AST and ALT = 3.5 x ULN; 14. LVEF = 55% on cardiac ultrasound; 15. If female, neither pregnant nor lactating; 16. Women of child-bearing potential: a. Negative pregnancy test at screening; b. Agreement to use appropriate contraception methods from study entry to 6 months after the last day of treatment; 17. Male patients agree to use contraception methods from study entry to 6 months after the last day of treatment; 18. Provide written informed consent; 19. Ability to comply with study procedures. Part B : 1. Age = 18 years; 2. Diagnosis of NSCLC with confirmed squamous or non-squamous tumour histology, without known EGFR mutation and with known KRAS status; 3. Archived tumour sample available; 4. Advanced or metastatic disease (Stage IIIb or IV) ; 5. No previous systemic treatment with chemotherapy, targeted therapy or investigational agents (except adjuvant therapy if > 6 months ago) ; 6. Candidate for treatment with cisplatin/pemetrexed or cisplatin/gemcitabine as determined by the Investigator; 7. Measurable disease by the RECIST criteria; 8. ECOG performance score 0 - 1; 9. Life expectancy = 3 months; 10. Absolute neutrophil count = 1 500/µL; 11. Platelets = 100 000/µL; 12. Creatinine clearance = 60 mL/minutes (Cockroft – Gault formula); 13. AST and ALT = 2.5 x ULN; in case of documented liver metastases, AST and ALT = 3.5 x ULN; 14. LVEF = 55% on cardiac ultrasound; 15. If female, neither pregnant nor lactating; 16. Women of child-bearing potential: a. Negative pregnancy test at screening; b. Agreement to use appropriate contraception methods from study entry to 6 months after the last day of treatment. 17. Male patients agree to use contraception methods from study entry to 6 months after the last day of treatment; 18. Provide written informed consent; 19. Ability to comply with study procedures. Part C : 1. Age = 18 years; 2. Diagnosis of NSCLC with confirmed squamous or non-squamous tumour histology, without known EGFR mutation and with known KRAS status; 3. Archived tumour sample available unless previous participant in Part B; 4. Advanced or metastatic disease (Stage IIIb or IV) ; 5. One of these two criteria should be fulfilled: a) Previous participant of Part B with PD under study treatment or b) New patient in case of futility of the interim analysis of Part B or in case of an insufficient number of patients enrolling from Part B with PD after dual chemotherapy with cisplatin/pemetrexed or cisplatin/gemcitabine or for any other re
Exclusion criteria
Exclusion criteria: Part A : 1. Unresolved toxicity from previous treatment; 2. Symptomatic brain metastases; 3. For patients on docetaxel: Serum bilirubin levels > ULN associated with serum ALP levels > 6 times ULN; 4. Gastro-intestinal disorders that could affect drug absorption (including, but not limited to, major abdominal surgery, significant bowel obstruction, ulcerative colitis, Crohn’s disease); 5. Concurrent treatment with any other systemic anti-cancer therapy; 6. Concomitant treatment with any drug on the prohibited medication list (provided separately); 7. Serious concomitant uncontrolled medical conditions. Part B : 1. Unresolved toxicity from previous treatment; 2. Symptomatic brain metastases; 3. Gastro-intestinal disorders that could affect drug absorption (including, but not limited to, major abdominal surgery, significant bowel obstruction, ulcerative colitis, Crohn’s disease); 4. Concurrent treatment with any other systemic anti-cancer therapy; 5. Concomitant treatment with any drug on the prohibited medication list (provided separately); 6. Serious concomitant uncontrolled medical conditions. Part C : 1. Unresolved toxicity from previous treatment; 2. Symptomatic brain metastases; 3. Serum bilirubin levels > ULN associated with serum ALP levels > 6 times ULN; 4. Gastro-intestinal disorders that could affect drug absorption (including, but not limited to, major abdominal surgery, significant bowel obstruction, ulcerative colitis, Crohn’s disease) ; 5. Concurrent treatment with any other systemic anti-cancer therapy; 6. Concomitant treatment with any drug on the prohibited medication list (provided separately); 7. Serious concomitant uncontrolled medical conditions.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A :To determine the MTD 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. Part B : To compare the effect of adding Debio 0932 to combination chemotherapy with cisplatin/pemetrexed and cisplatin/gemcitabine on the rate of PFS at 6 months in first-line therapy of patients with Stage IIIb or IV NSCLC. Part C : To compare the effect of adding Debio 0932 to docetaxel on the change in tumour size in second-line therapy of patients with Stage IIIb or IV NSCLC. ;Secondary Objective: Part A: Investigate for Debio 0932, in combination with cisplatin/pemetrexed, cisplatin/gemcitabine, and docetaxel:1. RD 2. Safety;3. PK & potential for drug-drug interactions;4. Anti-tumour activity;5. PD biomarkers of activity Part B:Compare between treatment arms:1. Best overall response rate;2. Duration of objective response;3. Change in tumour size from baseline until 6 months;4. Overall survival;5. Incidence of new symptomatic brain metastases. Investigate for Debio 0932, in combination with cisplatin/pemetrexed and cisplatin/gemcitabine: 6. Safety; 7. PK and PD profile Part C: To compare between treatment arms:1. Best overall response rate; 2. Duration of objective response;3. PFS at 6 Months;4. Overall survival;5. Incidence of new symptomatic brain metastases. To investigate for Debio 0932, in combination with docetaxel: 6. Safety;7. PK and PD profile. Parts A, B & C: Pharmacogenomic, tumour pharmacogenetic, proteomic, & pharmacogenetic factors predictive of response.;Primary end point(s): Part A : Occurrence of DLTs. Part B : Percentage of patients with PFS at 6 months. Part C : Change in tumour size from baseline until 6 months. ;Timepoint(s) of evaluation of this end point: At end of each (Parts A, B and C) study treatment phase. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A : 1. Change in vital signs, ECG and ECOG PS. 2. Incidence of AEs and SAEs according to NCI-CTCAE criteria. 3. Incidence of laboratory abnormalities according to NCI-CTCAE criteria. 4. Incidence of treatment discontinuations due to AEs and SAEs. 5. Change in LVEF. 6. Pharmacokinetic parameters of Debio 0932 and its metabolite Debio 0932-MET1 in plasma at steady state alone (on Day 21) and in combination with cisplatin/pemetrexed, cisplatin/gemcitabine, and docetaxel (on Day 22): C0h, Cmax, tmax, AUC0-tlast, AUC0-t, Css av, FI, ?z, t1/2, CL/F, and Vz/F calculated for all patients using non-compartmental analysis. 7. Pharmacokinetic parameters of cisplatin (total and unbound)/pemetrexed, cisplatin (total and unbound)/gemcitabine, and docetaxel in plasma after single infusion alone (on Day 1) and in combination with Debio 0932 at steady-state (on Day 22): Cmax, AUC0-tlast, AUC0-8, ?z, t1/2, MRT, CL, Vss, and Vz calculated for all patients using non-compartmental analysis. 8. Best overall response, i.e., best response recorded from start of study treatment until study end. 9. Optional exploration of pharmacodynamic biomarkers in plasma and PBMCs. 10. Pharmacogenomic, tumour pharmacogenetic, proteomic, and pharmacogenetic factors predictive of response to Debio 0932. Part B : 1. Best overall response, i.e. best response recorded from start of study treatment until study end. 2. Duration of objective response. 3. Change in tumour size from baseline until 6 months. 4. Overall survival. 5. In patients without brain metastases at baseline: incidence of new symptomatic brain metastases. 6. Safety and tolerability (vital signs, ECG, ECOG PS, LVEF and AEs, SAEs, and laboratory abnormalities according to NCI-CTCAE criteria). 7. Optional exploration of pharmacodynamic biomarkers in plasma and PBMCs. 8. Pharmacogenomic, tumour pharmacogenetic, proteomic, and pharmacogenetic factors predictive of response to Debio 0932. 9. If appl | — |
Countries
Hungary, Spain, United Kingdom
Contacts
Public ContactRegulatory Affairs Project Manager
INC Research
Outcome results
None listed