Page 11 - Delaware Medical Journal - March/April 2021

CANCER CLINICAL TRIAL
Alliance A031704: PD-Inhibitor (Nivolumab) and Ipilimumab,
Followed by Nivolumab vs. VEGF TKI Cabozantinib with Nivolumab:
A Phase III Trial in Metastatic, Untreated Renal Cell Cancer [PDIGREE]
Primary Objectives:
To compare the overall survival (OS) in patients with metastatic RCC treated with ipilimumab-nivolumab, followed by either nivolumab or cabozantinib-nivolumab.
Secondary Objectives:
•To determine PFS of patients treated with nivolumab versus nivolumab-cabozantinib
•To evaluate the 12-month complete response rate in patients treated with ipilimumab-nivolumab followed
by cabozantinib-nivolumab, versus ipilimumab-nivolumab followed by nivolumab
•To evaluate the rates of discontinuing therapy at 1 year
•To compare objective response rates for patients treated with ipilimumab-nivolumab followed by cabozantinib- nivolumab, versus ipilimumab-nivolumab followed by nivolumab.
•To document the adverse event profile of ipilimumab- nivolumab followed by cabozantinib-nivolumab.
Biomarker Studies and QOL Objectives
(See protocol for more information)
STEP 1 Registration Eligibility Criteria:
•Histologic Documentation: Histologically documented renal cell carcinoma with clear cell component, including patients who have sarcomatoid features. Stage: Any metastatic disease, including visceral, lymph node, other soft tissue and bone, measurable
•Intermediate or poor risk patients per IMDC criteria will be eligible (1 or more of the following: KPS<80, <1 year from diagnosis to systemic treatment, hemoglobin less than LLN, corrected calcium concentration greater than ULN, absolute neutrophil count greater than ULN, platelet count>ULN)
•CNS disease permitted, if stable and not otherwise causing symptoms or needing active treatment
•Karnofsky performance status ≥70%; age ≥ 18 years; not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects; required initial lab values
•No prior treatment with PD-1, PD-L1, or CTLA-4
targeting agents (including but not limited to nivolumab, pembrolizumab, pidilizumab, durvalumab, atezolizumab, tremelimumab, and ipilimumab), or any other drug or antibody specifically targeting T-cell co-stimulation or checkpoint pathways
•No prior previous systemic therapy for renal cell carcinoma (prior HD IL-2 [>28 days] and prior adjuvant sunitinib >180 days since completion are allowed)
•No cancer therapy less than 28 days prior to registration; this includes radiation therapy, except for bone lesions less than 14 days prior to registration. There must be a complete recovery and no ongoing complications from radiotherapy.
STEP 2 Registration Eligibility Criteria:
•Completion of at least 1 cycle of ipilimumab/nivolumab
and no more than 56 days from last dose.
•Resolution of any treatment-related adverse events to grade 1 or less per dose modification section
•No more than 56 days from last dose of ipilimumab/ nivolumab.
Treatment:
Induction therapy: Ipilimumab 1mg/kg IV and nivolumab 3mg/kg IV every 21 days, for up to 4 cycles. Following the induction phase and radiographic assessment at week 12, patients will be placed in one of the three treatment plans below: until (further) disease progression or unacceptable adverse event.
Progression of disease (PD): Cabozantinib 60mg by mouth daily (on an empty stomach).
Complete response (CR): Nivolumab 480 mg IV every 28 days until disease progression or unacceptable adverse event, or 1 year if CR persists at 1 year.
Patients with non-CR/non-PD will be randomized to either of the following treatments:
•Arm A: Nivolumab 480 mg IV every 28 days •Arm B: Nivolumab 480 mg IV every 28 days and
cabozantinib 40mg by mouth (on an empty stomach) daily
For information regarding this clinical trial or if you would like to have the list of open protocols emailed to you, please call the Cancer Research Office at (302) 623-4450 or email akee@christianacare.org.
Del Med J | March/April 2021 | Vol. 93 | No. 2 59