Neoadjuvant Immune Checkpoint Blockade in Resectable Malignant Pleural Mesothelioma
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab Injection
- Conditions
- Mesothelioma
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Enrollment
- 30
- Locations
- 3
- Primary Endpoint
- Feasibility of neoadjuvant nivolumab +/- ipilimumab in patients with resectable MPM who complete of neoadjuvant treatment and proceed to surgery
- Status
- Active, not recruiting
- Last Updated
- 10 months ago
Overview
Brief Summary
The proposed study will evaluate the safety and feasibility of neoadjuvant nivolumab +/- ipilimumab in resectable MPM. In addition, maintenance nivolumab will be administered for 1 year following completion of standard bi-/tri-modality therapy.
Detailed Description
For Arm A 15 patients with resectable MPM will be enrolled and receive preoperative nivolumab, 240mg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10). Subsequent to full accrual to Arm A, 15 patients with resectable MPM will be enrolled and receive preoperative nivolumab, 3mg/kg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) + ipilimumab 1mg/kg IV on Day -42 prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Men and women ≥ 18 years old
- •Primary tumor amenable to safe research biopsy. A tumor biopsy is required for study entry.
- •Histology proven epithelial or biphasic MPM
- •Diagnostic core biopsy specimens must be reviewed by faculty pathologist at SKCC, MDACC, or UMGCCC.
- •Either a formalin fixed paraffin block that has been confirmed by a pathologist to contain tumor or a minimum of twenty 5-micron tissue sections (slides) of tumor biopsy sample must be available for biomarker evaluation (study pathologist must review for adequacy of sampling). This can be obtained from archived tissues if adequate, or from a new biopsy as needed.
- •Stage I-III and deemed to be potentially surgically resectable as assessed by faculty surgeon at SKCC, MDACC, or UMGCCC
- •ECOG performance status 0-1
- •Adequate organ function as follows:
- •Leukocytes ≥ 2,000/mm3
- •Absolute neutrophil count (ANC) ≥ 1000/mm3
Exclusion Criteria
- •Stage I-III disease but deemed to be unresectable, a poor surgical candidate, or unfit for study therapy as assessed by study investigators
- •Pure sarcomatoid histology
- •Subjects are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- •Subjects are excluded if they have a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily 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. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab-containing regimen.
- •Administration of chemotherapy or any other cancer therapy in the pre-operative period.
- •Subjects with active concurrent malignancies are excluded i.e. cancers other than MPM (except non-melanoma skin cancers, cervical dysplasia, and in situ cancers of bladder, stomach, breast, colon and cervix).
- •Subjects with a history of symptomatic interstitial lung disease.
- •Active systemic infection requiring therapy, as well as positive tests for hepatitis B surface antigen or hepatitis C antibody.
- •Known positive history or positive test for human immunodeficiency virus or Acquired Immunodeficiency Syndrome (AIDS).
- •History of allergy to study drug components.
Arms & Interventions
Arm A Nivolumab Only
Receive preoperative nivolumab, 240mg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).
Intervention: Nivolumab Injection
Arm B Nivolumab + Ipilimumab
Receive preoperative nivolumab, 3mg/kg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) + ipilimumab 1mg/kg IV on Day -42 prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).
Intervention: Nivolumab Injection
Arm B Nivolumab + Ipilimumab
Receive preoperative nivolumab, 3mg/kg IV, on Day -42, -28 and Day -14 (+/- two days for each timepoint) + ipilimumab 1mg/kg IV on Day -42 prior to planned surgery on Day 0 (to allow for scheduling surgery may take place between Day -3 and Day +10).
Intervention: Ipilimumab Injection
Outcomes
Primary Outcomes
Feasibility of neoadjuvant nivolumab +/- ipilimumab in patients with resectable MPM who complete of neoadjuvant treatment and proceed to surgery
Time Frame: up to 5 years
Feasibility as measured by the number of participants who complete of neoadjuvant treatment with nivolumab +/- ipilimumab and proceed to surgery without extended treatment-related delay (\>24 days from preplanned surgery date).
Safety Profile of neoadjuvant nivolumab +/- ipilimumab in patients with resectable malignant pleural mesothelioma (MPM) with grade III/IV adverse events defined by CTCAE v5.0
Time Frame: up to 5 years
Number of participants with grade III/IV adverse events defined by CTCAE v5.0, occurring within 100 days of last study drug administration or 30 days post-surgery (whichever is longer).
Secondary Outcomes
- Pathological Response to neoadjuvant nivolumab +/- ipilimumab in resected tumor and lymph nodes in patients with resectable MPM defined as ≤10% residual viable tumor cells and pathologic complete response(5 years)
- Radiographic Response to neoadjuvant nivolumab +/- ipilimumab utilizing RECIST 1.1(5 years)
- Toxicity as assessed by number of participants experienced grade III/IV adverse events as defined by CTCAE v5.0 within 100 days of last study drug administration(up to 100 days post-intervention)