A Prospectively Designed Study to Assess the Relationship Between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients With Advanced Melanoma or Bladder Cancer Treated With Nivolumab or Nivolumab Plus Ipilimumab (CA209-260)
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab plus Ipilimumab
- Conditions
- Bladder Cancer
- Sponsor
- Memorial Sloan Kettering Cancer Center
- Enrollment
- 81
- Locations
- 5
- Primary Endpoint
- Confirmed Objective Response in Bladder Cancer Participants to Nivolumab Monotherapy
- Status
- Completed
- Last Updated
- 9 months ago
Overview
Brief Summary
The purpose of this study is to investigate the characteristics of tumors in patients treated with nivolumab and to identify features that help to predict a good or bad response to this drug.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Subjects must have signed and dated an IRB approved written informed consent in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
- •Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study.
- •Pathologically confirmed locally advanced or metastatic disease per the treating institution's standard of care of the following tumor types
- •Subjects with histologically confirmed locally advanced/unresectable or metastatic melanoma who meet all of the following criteria:
- •i. Subjects have received any number of prior lines of therapy or may be treatment naïve ii. If the subject has been treated with a prior line of therapy, they must have had disease progression or be refractory to treatment
- •b. Subjects with histologically or cytologically confirmed locally advanced/unresectable or metastatic urothelial carcinoma (including mixed histologies of urothelial carcinoma with elements of other subtypes) of the renal pelvis, ureter, bladder or urethra (referred to broadly in this protocol as "bladder cancer") who meet the following criteria: i. Subjects must have disease progression or refractory disease after their prior line of therapy. Subjects must have had at least 1 platinum based chemotherapy regimen for the treatment of metastatic or locally advanced unresectable disease. Subjects may have received any number of prior lines of therapy OR
- •ii. Subjects with disease recurrence within 1 year of a platinum based neoadjuvant or adjuvant therapy for bladder cancer.
- •iii. The subject actively refuses chemotherapy for the treatment of metastatic or locally advanced disease considered as standard treatment for this disease stage (i.e. a patient who has relapsed \>1 year after treatment with neoadjuvant or adjuvant chemotherapy), despite being informed by the investigator about the treatment options. The subject's refusal must be documented.
- •Subjects must have measurable disease by CT scans or MRI per RECIST 1.1 criteria. Radiographic tumor assessment must be performed within 28 days prior to first dose of study drug.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
Exclusion Criteria
- •Active brain metastases or leptomeningeal metastases. Subjects with treated brain metastases are eligible if they meet all of the following criteria:
- •Must be at least 28 days since craniotomy and resection, stereotactic radiosurgery, or whole brain radiotherapy.
- •Must have no evidence of progression for at least 4 weeks after treatment is complete and within 28 days prior to first dose of study drug administration.
- •Must have no requirement for immunosuppressive doses of systemic corticosteroids (\> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
- •Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy or interfere with the interpretation of study results.
- •Other prior malignancy active within the previous 2 years except for local or organ confined early stage cancer that has been definitively treated with curative intent or does not require treatment, does not require ongoing treatment, has no evidence of active disease and has a negligible risk of recurrence and is therefore unlikely to interfere with the endpoints of the study.
- •Subjects with active autoimmune disease, symptoms or conditions. Subjects with vitiligo, type I diabetes, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, asymptomatic laboratory evidence of autoimmune disease (e.g.: +ANA, +RF, antithyroglobulin antibodies), or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
- •Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first dose of study drug. Inhaled or topical steroids, and adrenal replacement steroid doses are permitted in the absence of active autoimmune disease.
- •Subjects who have received prior therapy with any T cell co-stimulation or checkpoint pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137; or other medicines specifically targeting T cells are prohibited. Prior therapy with BCG is permitted. Prior IL-2 is permitted.
- •All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (CTCAE version 4) or baseline before administration of study drug. Subjects with toxicities attributed to prior anti-cancer therapy and which are not expected to resolve and result in long lasting sequelae such as neuropathy after platinum-based therapy, are permitted to enroll.
Arms & Interventions
Melanoma Cancer Patients
All eligible patients with melanoma will receive ipilimumab at a dose of 3 mg/kg combined with nivolumab at a dose of 1 mg/kg. The ipilimumab and nivolumab will be dosed every 3 weeks for 4 doses. Thereafter, patients may be eligible to continue to receive nivolumab monotherapy at a dose of 240 mg administered every 2 weeks OR nivolumab at dose of 480mg every 4 weeks for up to 2 years.
Intervention: Nivolumab plus Ipilimumab
Bladder Cancer Patients
All eligible patients with bladder cancer will receive nivolumab at a dose of 240 mg administered every 2 weeks for up to 2 years, if the patient is clinically benefitting, the PI and treating investigator may elect to continue treatment beyond 2 years. All eligible patients with bladder cancer will receive nivolumab at a dose of 240 mg administered every 2 weeks for up to 2 years, if the patient is clinically benefitting, the PI and treating investigator may elect to continue treatment beyond 2 years.
Intervention: Nivolumab
Outcomes
Primary Outcomes
Confirmed Objective Response in Bladder Cancer Participants to Nivolumab Monotherapy
Time Frame: From treatment start, up to 2 years from initial dose of nivolumab.
Primary clinical endpoint was proportion of patients who achieve a confirmed objective response rate (per RECIST 1.1) to nivolumab monotherapy in bladder cancer patients progressing on initial nivolumab monotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Confirmed Objective Response for Bladder Cancer Patients to Ipilimumab and Nivolumab Combination Therapy in Patients Progressing on Initial Nivolumab Monotherapy
Time Frame: From treatment start, up to 2 years from initial dose of nivolumab.
Primary clinical endpoint was proportion of patients who achieve a confirmed objective response rate (per RECIST 1.1) to ipilimumab and nivolumab combination therapy in bladder cancer patients progressing on initial nivolumab monotherapy.
Secondary Outcomes
- Tumor Mutational Burden for Evaluable Bladder Cancer Participants(At baseline)