MM and NSCLC patients resistant to anti-PD-1/PD-L1 therapy MedDRA version: 20.0 Level: SOC Classification code 10029104 Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps) System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: YERVOY
Product Code: [NA]
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 477202-00-9
Current Sponsor code: BMS-734016
Concentration unit: mg/kg milligram(s)/kilog
Sponsors
FONDAZIONE NIBIT NETWORK ITALIANO PER LA BIOTERAPIA DEI TUMORI
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Signed Written Informed Consent Willing and able to give written informed consent. Target Population Subjects must fulfill all of the following inclusion criteria: Men and women of and over 18 years old 1) Target Population Melanoma cohort A a) Histologic diagnosis of malignant melanoma b) Unresectable Stage III/Stage IV melanoma patients with resistance to anti-PD-1/PD-L1 and measurable lesions by CT or MRI per iRECIST/RECIST criteria that can be amenable to biopsy c) Only one line of immunotherapy for advanced (unresectable Stage III or Stage IV) disease with anti-PD-1/PDL1 and its combinations; if BRAF mutant one line of targeted therapy is allowed prior to anti-PD-1/PDL1therapy. 2) Target Population NSCLC cohort B a) Histologic or cytologic diagnosis of NSCLC lacking EGFR-sensitizing mutation and/or ALK/ROS1 translocation. b) Stage IV NSCLC patients with primary resistance to anti-PD-1/PD-L1 and measurable lesions by CT or MRI per iRECIST/RECIST criteria that can be amenable to biopsy. c) Only one line of immunotherapy for advanced (unresectable Stage III or Stage IV) disease with anti-PD-1/PDL1 or its combinations; one line of chemotherapy is allowed prior to anti-PD-1/PDL-1 therapy. 3) confirmed PD 4) 4 weeks or greater since last treatment and 5) Must have recovered from any acute toxicity associated with prior therapy 6) Life expectancy greater than 16 weeks 7) Subjects with adequate organ function defined as: a) WBC =3500/uL b) ANC =2000/uL c) Platelets = 100 x 103/uL d) Hemoglobin = 9 g/dL e) Creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 184
Exclusion criteria
Exclusion criteria: 1) Sex and Reproductive Status a) Women who are pregnant or breastfeeding; b) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 6 months after the study; c) Women with a positive pregnancy test on enrollment or prior to investigational product administration; d2) Target Disease Exceptions Nivolumab Ipilimumab Guadecitabine NIBIT-ML-1 Clinical Protocol 27/80 a) Any malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix b) Primary ocular melanoma. 3) Medical History and Concurrent Diseases a) Symptomatic brain metastases requiring immediate local intervention (radiotherapy (RT) and/or surgery); b) Leptominingeal involvement by disease; c) Autoimmune disease: Patients with a documented history of Inflammatory Bowel Disease, including ulcerative colitis and Crohn’s disease are excluded from this study as are patients with a documented history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener’s Granulomatosis] and autoimmune hepatitis. Subjects with motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome) are also excluded from this study; d) Any underlying medical condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea. 4) Prohibited Treatments and/or Therapies a) Concomitant therapy with any anti-cancer agent; immunosuppressive agents; any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month prior to or after any dose of study drug); surgery or radiotherapy (except palliative surgery and/or radiotherapy to treat a non-target symptomatic lesion or to the brain after Sponsor approval); other investigational anti-cancer therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses); b) Previous treatment with other investigational products, including cancer immunotherapy, within 30 days; c) Prior treatment with anti-CTLA-4, except in adjuvant setting) Sexually active fertile men not using effective birth control if their partners are WOCBP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the immune-related Objective Response Rate (i-ORR) of nivolumab combined with ipilimumab and guadecitabine or nivolumab combined with ipilimumab, in MM and NSCLC patients resistant to anti-PD-1/PD-L1 therapy.;Secondary Objective: To assess safety, tolerability and feasibility of the combinations To assess the objective response rate (ORR), (assessed using RECIST v. 1.1 criteria) of nivolumab combined with ipilimumab and guadecitabine or nivolumab combined with ipilimumab, in MM and NSCLC patients resistant to anti-PD-1/PD-L1 therapy. To further describe efficacy using the following tumor response indicators (assessed using iRECIST/RECIST v 1.1 criteria) and clinical endpoints: Disease Control Rate, Duration of response, Time to response and Progression-Free Survival, Overall Survival (OS) as summarized by median Survival and Survival rate at one and two years.;Primary end point(s): To assess the immune- related objective response rate (i-ORR) (assessed using iRECIST criteria) of nivolumab combined with ipilimumab and guadecitabine or nivolumab combined with ipilimumab, in MM and NSCLC patients resistant to anti-PD-1 therapy.;Timepoint(s) of evaluation of this end point: 20 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 20 weeks;Secondary end point(s): Secondary Objectives: - To assess safety, tolerability and feasibility of the combinations - To assess the objective response rate (ORR) (assessed using RECIST v. 1.1 criteria) of nivolumab combined with ipilimumab and guadecitabine or nivolumab combined with ipilimumab, in MM and NSCLC patients resistant to anti-PD-1 therapy. - To further describe efficacy using the following tumor response indicators (assessed using RECIST v 1.1and iRECIST criteria) and clinical endpoints: Disease Control Rate, Duration of response, Time to response and Progression-Free Survival, Overall Survival as summarized by median Survival and Survival rate at one and two years | — |
Countries
Italy
Contacts
Public ContactMedical Oncology and Immunotherapy
Azienda Ospedaliera Universitaria Senese
Outcome results
None listed