A Study of NIVO Plus IPI and Guadecitabine or NIVO Plus IPI in Melanoma and NSCLC Resistant to Anti-PD1/PDL1 (NIBIT-ML1)
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|ClinicalTrials.gov Identifier: NCT04250246|
Recruitment Status : Not yet recruiting
First Posted : January 31, 2020
Last Update Posted : January 31, 2020
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Non Small Cell Lung Cancer||Drug: Ipilimumab plus nivolumab plus guadecitabine Drug: Ipilimumab plus nivolumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||184 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomized, non-comparative, phase II study designed according to a two stages optimal design by Simon|
|Masking:||None (Open Label)|
|Official Title:||A Randomized, run-in, Multi-center, Phase II Study of Nivolumab Combined With Ipilimumab and Guadecitabine or Nivolumab Combined With Ipilimumab in Melanoma and NSCLC Patients Resistant to Anti-PD-1/PD-L1 (NIBIT-ML1)|
|Estimated Study Start Date :||March 2020|
|Estimated Primary Completion Date :||March 2023|
|Estimated Study Completion Date :||March 2025|
Experimental: Ipilimuamb plus nivoluamb plus guadecitabine
ipilimumab plus nivolumab combined with guadecitabine
Drug: Ipilimumab plus nivolumab plus guadecitabine
Cohort A Melanoma ARM A Guadecitabine: 30-45 mg/m2 s.c./day 1-5 q21 x 4 cycles and from W13 q28 x 6 cycles Ipilimumab: 3 mg/Kg i.v. plus nivolumab 1 mg/Kg i.v. on W1, 4, 7 and 10 and from W14 nivolumab 480 mg i.v. q4 wks for 2 years
Cohort B NSCLC ARM A Guadecitabine: 30-45 mg/m2 s.c./day 1-5 q21 x 4 cycles and from W13 q28 x 6 cycles Ipilimumab: 1 mg/Kg i.v.q 6wks plus nivolumab 3 mg/Kg i.v. q2 wks until W13, then ipilimumab: 1 mg/Kg i.v. q 6wks plus nivolumab 480mg i.v. q4wks for 2 years
Active Comparator: Ipilimumab plus nivolumab
Ipilimumab plus nivolumab
Drug: Ipilimumab plus nivolumab
Cohort A Melanoma ARM B Ipilimumab: 3 mg/Kg i.v. plus nivolumab 1 mg/Kg i.v. on W1, 4, 7 and 10 and from W14 nivolumab 480 mg i.v. q4 wks for 2 years
Cohort B NSCLC ARM B Ipilimumab: 1 mg/Kg i.v. q 6wks plus nivolumab 3 mg/Kg i.v. q2 wks until W13, then ipilimumab: 1 mg/Kg i.v. q6 wks plus nivolumab 480mg i.v. q4wks for 2 years.
- Immune-related Objective Response Rate (iORR) [ Time Frame: 24 weeks ]Immune-related Objective Response Rate (iORR) is the proportion of treated subjects with an iBOR of confirmed iCR or confirmed iPR.
- Safety of guadecitabine in combination with ipilimumab and nivolumab [ Time Frame: 2 years ]Reporting of safety, extent of exposure, concomitant medications and discontinuation of study therapy will be based on all treated subjects; for on-study laboratory test results, all treated subjects with at least one on-study laboratory measurement available will be included in the analysis. The reporting period for safety data will be from the date of first dose received on this study to 100 days after the last dose is received. Serious adverse events are reported from the time of consent forward for all subjects. All subjects who received at least one dose of study treatment will be evaluated for safety parameters
- Obiective Response Rate (ORR) [ Time Frame: 24 weeks ]Objective Response Rate (ORR) is the proportion of treated subjects with a BOR of CR or PR per RECIST 1.1.
- Disease Control Rate (DCR) [ Time Frame: 24 weeks ]Disease Control Rate (DCR) is the proportion of treated subjects with a BOR of confirmed CR, confirmed PR or SD, based on RECIST 1.1 and iRECIST.
- Duration of response (DoR) [ Time Frame: 2 years ]Duration of Response (DoR) for the subjects whose BOR is CR or PR will be defined as the time between the date of response of confirmed CR or confirmed PR (whichever occurs first) and the date of PD or death (whichever occurs first), based on RECIST 1.1 and iRECIST.
- Time to response (TTR) [ Time Frame: 24 weeks ]Time to Response (TTR) is defined as the time from first dosing date until the measurement criteria are first met for overall response of PR or CR (whichever status comes first, and provided it is subsequently confirmed), , based on RECIST 1.1 and iRECIST.
- Progression Free Survival (PFS) [ Time Frame: 2 years ]Progression free survival (PFS) per RECIST 1.1 and iRECISTwill be defined as the time between the date of randomization and the date of progression and or confirmed PD (according to RECIST 1.1 and iRECIST) or death, whichever occurs first.
- Overall Survival (OS) [ Time Frame: 2 years ]Overall Survival (OS) is defined as the time from randomization until the date of death. For those subjects who have not died, OS will be censored at the recorded last date of subject contact, and for subjects with a missing recorded last date of contact, OS will be censored at the last date the subject was known to be alive. Any efforts will be made to know the date of death.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04250246
|Contact: Anna Maria Di Giacomo, MDfirstname.lastname@example.org|
|Contact: Michele Maio, MD PhDemail@example.com|
|Principal Investigator:||Anna Maria Di Giacomo, MD||Center for Immuno-Oncology, University Hospital of Siena|