A Phase II Study to Evaluate Adaptive Dosing of Ipilimumab and Nivolumab Combination Immunotherapy
Overview
- Phase
- Phase 2
- Intervention
- ipilimumab
- Conditions
- Metastatic Melanoma
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 70
- Locations
- 14
- Primary Endpoint
- objective response rate
- Status
- Active, not recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
This study will help determine whether 2 doses of the combination (ipilimumab + nivolumab) is sufficient for patients with early benefit compared to the usual way of trying to give 4 doses. If patients do not show early benefit after 2 doses, patients will be able to continue with additional ipilimumab + nivolumab, even beyond the standard 4 doses if felt in the best interest of the patient.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologic diagnosis of unresectable III or stage IV metastatic melanoma.
- •Subjects must have at least 1 extracranial, unresectable, non-bony lesion that is measurable radiographically (based on RECIST 1.1).
- •No prior CTLA-4 or PD-1/PD-L1 therapy for the treatment of metastatic disease.
- •ECOG performance status of 0-
- •Life expectancy ≥ 4 months.
- •Screening laboratory parameters:
- •White blood cell (WBC) count ≥ 2000/μL;
- •Absolute neutrophil count (ANC) ≥ 1500/μL;
- •Platelets ≥ 100,000/μL;
- •Hemoglobin (Hgb) ≥ 9 g/dL;
Exclusion Criteria
- •Active autoimmune disease or any condition requiring systemic treatment with either corticosteroids (\>10 mg daily of prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
- •History of motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre Syndrome, Myasthenia Gravis).
- •Other active, concurrent malignancy that requires ongoing systemic treatment or interferes with radiographic assessment of melanoma response as determined by the investigator.
- •Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C infection. Antibody to Hepatitis B or C without evidence of active infection may be allowed.
- •History of severe allergic reactions to any unknown allergens or any components of the study drugs.
- •Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
- •Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
- •Lack of availability for immunological and clinical assessments or post-study follow-up contact to determine relapse and survival.
- •Women who are breastfeeding or who are pregnant as evidenced by a positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) performed within 14 days of the first dose of study drug and by a urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours of the first dose of study drug(s).
- •Any condition that, in the clinical judgment of the treating physician, is likely to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
Arms & Interventions
ipilimumab and nivolumab
Pts will receive 2 doses of ipilimumab 3mg/kg + nivolumab 1mg/kg every 3 weeks. Week 6, if pts have achieved a favorable antitumor effect by RECIST will begin maintenance nivolumab alone at 480mg every 4 weeks for 2 doses (week 6 \& week 10) \& repeat response assessments at week 12. If pts don't achieve a favorable antitumor effect at week 6, pt will get 2 additional doses of ipilimumab + nivolumab every 3 weeks \& then will be assessed for response at week 12. If pts haven't achieved a favorable antitumor effect by week 12, if felt in the best interest for the pt as determined by the PI, pts may continue getting additional doses of ipilimumab + nivolumab with response reassessments after every 2 doses. Maintenance nivolumab will continued until unacceptable toxicity or confirmed disease progression. If pts have had an initial clinical benefit from therapy \& subsequently experience progressive disease at any time, reinduction with combination ipilimuma+ nivolumab will be allowed.
Intervention: ipilimumab
ipilimumab and nivolumab
Pts will receive 2 doses of ipilimumab 3mg/kg + nivolumab 1mg/kg every 3 weeks. Week 6, if pts have achieved a favorable antitumor effect by RECIST will begin maintenance nivolumab alone at 480mg every 4 weeks for 2 doses (week 6 \& week 10) \& repeat response assessments at week 12. If pts don't achieve a favorable antitumor effect at week 6, pt will get 2 additional doses of ipilimumab + nivolumab every 3 weeks \& then will be assessed for response at week 12. If pts haven't achieved a favorable antitumor effect by week 12, if felt in the best interest for the pt as determined by the PI, pts may continue getting additional doses of ipilimumab + nivolumab with response reassessments after every 2 doses. Maintenance nivolumab will continued until unacceptable toxicity or confirmed disease progression. If pts have had an initial clinical benefit from therapy \& subsequently experience progressive disease at any time, reinduction with combination ipilimuma+ nivolumab will be allowed.
Intervention: nivolumab
Outcomes
Primary Outcomes
objective response rate
Time Frame: at 6 weeks
RECIST 1.1.