Actively Recruiting
PRE-surgical NEOadjuvant Sandwich Immunotherapy With HIF inhibition in Renal Cell Carcinoma (PRENEOSHIFT-RCC)
Led by Dana-Farber Cancer Institute · Updated on 2026-03-20
32
Participants Needed
3
Research Sites
86 weeks
Total Duration
On this page
Sponsors
D
Dana-Farber Cancer Institute
Lead Sponsor
A
Arcus Biosciences, Inc.
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and effectiveness of the drug casdatifan alone and in combination with zimberelimab for people with clear cell renal cell carcinoma (ccRCC) that can be surgically removed. This phase 2, randomized, open-label trial involves participants with specific stages of ccRCC and aims to understand how these treatments work before surgery. The study drugs casdatifan, which is a HIF-2α inhibitor, and zimberelimab, a monoclonal antibody, have not yet been approved by the FDA for this cancer. Participants will be randomly assigned to one of two groups: one group will receive casdatifan alone, and the other will receive casdatifan plus zimberelimab. Both treatments are given in cycles lasting 21 days; casdatifan is taken orally daily, while zimberelimab is administered by intravenous infusion on the first day of each cycle for the combination group. After completing three cycles, participants will undergo standard surgical removal of their kidney tumor and then be followed for up to three years. During the study, participants will have multiple visits for screening, blood and urine tests, imaging scans such as CT, MRI, or PET, and other evaluations to monitor health and treatment effects. The main outcome measured is the reduction in tumor size before surgery, assessed around week 11. Safety is closely monitored through reports of side effects during treatment and for several months after surgery. Overall, participant involvement includes treatment cycles, surgery, follow-up visits, and various tests over an extended period.
CONDITIONS
Brief Title
Pre-NEOSHIFT-RCC: Neoadjuvant HIF-Inhibitor Immunotherapy in RCC
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adult patients age 18 years or older
- Histologically confirmed clear cell renal cell carcinoma by core-needle biopsy
- Stage cT2 RCC with grade 4 or sarcomatoid features, at least cT3 Nx RCC, or any cT with N+ disease planned for partial or radical nephrectomy
- Measurable primary renal tumor at least 10 mm by CT or MRI
- Planned surgical removal of the primary renal tumor
- ECOG performance status of 0-1
- Adequate organ and marrow function based on specified laboratory tests within 14 days before treatment
- No exercise-induced oxygen desaturation (oxygen saturation >92%)
- No active clinical pneumonitis at screening
- No history of severe chronic obstructive pulmonary disease
- Left ventricular ejection fraction above institutional lower limit of normal
- Negative pregnancy test for women of childbearing potential
- Agreement to use highly effective contraception during and after the study as specified
- Ability to understand and sign informed consent
- Ability to swallow tablets
You will not qualify if you...
- Prior systemic therapy for renal cell carcinoma
- Radiation therapy within 4 weeks before first study treatment dose
- Clear evidence of distant metastases (except planned lymph node removal during nephrectomy)
- Clinical pneumonitis or inflammatory lung disease at screening
- Use of complementary medications to treat the disease within 2 weeks before treatment
- Other active malignancy within the past year except certain cured or indolent cancers
- QTc interval 480 msec or greater
- Malabsorption conditions affecting oral medication absorption
- Major cardiovascular events within 6 months prior to treatment
- Uncontrolled or significant medical illnesses including serious heart, lung, gastrointestinal, or autoimmune conditions
- Use of systemic corticosteroids or immunosuppressive medications within 14 days before randomization
- Active infection requiring systemic treatment
- Positive tests for active hepatitis B or C, HIV infection with detectable viral load, or AIDS-related illness
- Serious non-healing wounds or fractures
- Uncompensated symptomatic hypothyroidism
- Moderate to severe liver impairment
- History of solid organ or stem cell transplant
- Major surgery within 4 weeks or minor surgery within 7 days before treatment
- Treatment with strong CYP3A4 inhibitors or inducers without adequate washout
- Psychiatric illness or substance use disorders interfering with study compliance
- Use of live vaccines within 28 days before treatment
- Current breastfeeding
- Known allergy to study treatment components
- Use of supplemental or intermittent oxygen therapy
- Any condition compromising safety or ability to complete the study as judged by the investigator
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 3 cycles of 21 days each
Participants receive oral casdatifan daily for 3 cycles of 21 days each. Participants in one group also receive an intravenous infusion of zimberelimab on Day 1 of each cycle.
Baseline visit and 3 treatment visits every 21 days
Duration - Up to 1 week
Participants undergo standard of care nephrectomy to remove the primary renal tumor.
1 surgical visit (in-person)
Duration - Up to 3 years
Participants are followed for safety and treatment outcomes including adverse events and tumor response for up to 3 years after surgery.
Visits scheduled periodically including a visit at 3 months post-surgery
Trial Site Locations
Total: 3 locations
1
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Not Yet Recruiting
2
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02215
Actively Recruiting
3
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Actively Recruiting
Research Team
W
Wenxin Xu, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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