Pre-NEOSHIFT-RCC: Neoadjuvant HIF-Inhibitor Immunotherapy in RCC

NCT07397611 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-595
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to see whether the drug casdatifan is safe and effective either by itself or in combination with the drug zimberelimab in participants with resectable clear cell renal cell carcinoma (ccRCC). The names of the study drugs involved in this study are:

• Casdatifan (a type of HIF-2α inhibitor)
• Zimberelimab (a type of monoclonal antibody)

Conditions

Renal Cell Carcinoma; Kidney Cancer; Kidney Neoplasm; Renal Carcinoma

Keywords

Renal Cell Carcinoma; Kidney Cancer; Kidney Neoplasm; Renal Carcinoma; ccRCC

Outcome Measures

Primary Outcomes (1)

• Tumor Size Reduction Rate

  Tumor size reduction rate is defined as the proportion of participants who achieve any decrease in the maximal dimension of the primary tumor.

  Disease assessment will occur at pre-surgery visit week 11 ± 2 weeks.

Secondary Outcomes (2)

• Global Adverse Events (AE) Rate

  Assessed from treatment start and continuing through the first long-term follow-up visit at 3 months post-surgery, for a total maximum duration of approximately 24 weeks.

• Treatment Related Adverse Events (TRAEs) Rate

  Assessed from treatment start and continuing through the first long-term follow-up visit at 3 months post-surgery, for a total maximum duration of approximately 24 weeks.

Study Arms (2)

Group A: Casdatifan

EXPERIMENTAL

16 participants will be enrolled and will complete the following: * Baseline visit * Cycle 1 through 3 (21 day cycles): --Days 1 - 21: Predetermined dose of Casdatifan 1x daily * standard of care nephrectomy * Follow up for up to 3 years

Drug: Casdatifan

Group B: Casdatifan + Zimberelimab

EXPERIMENTAL

* 16 participants will be enrolled and will complete the following: * Baseline visit * Cycle 1 through 3 (21 day cycles): * Days 1 - 21: Predetermined dose of Casdatifan 1x daily * Day 1: Predetermined dose of Zimberelimab * Standard of care nephrectomy * Follow up for up to 3 years

Drug: Casdatifan; Drug: Zimberelimab

Interventions

Casdatifan DRUG

HIF-2α inhibitor, tablet taken orally per protocol.

Also known as: C21H17F4NO3S, AB521

Group A: Casdatifan; Group B: Casdatifan + Zimberelimab

Zimberelimab DRUG

monoclonal antibody, multi-dose vial, via intravenous (through the vein) infusion, per protocol.

Also known as: AB122

Group B: Casdatifan + Zimberelimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients age ≥ 18 years.
• Histologically confirmed diagnosis of ccRCC by a core-needle biopsy. Patients who have not had prior biopsy may undergo screening if they have suspected RCC but can only proceed to registration if ccRCC (any component) is confirmed on the pre-treatment study biopsy.
• Stage cT2 RCC with grade 4 or sarcomatoid features, ≥cT3 Nx RCC, or cTany N+ RCC disease for which partial or radical nephrectomy is planned. For clinical staging, a kidney MRI is highly preferred over a CT Abdomen.
• Participants must have measurable disease i.e. a primary renal tumor that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT scan or MRI. See Section 11 (Measurement of Effect) for the evaluation of measurable disease.
• Participants must be planned for surgical resection of their primary renal tumor.
• ECOG performance status of 0-1.
• Participants must have adequate organ and marrow function, based upon meeting all of the following laboratory criteria within 14 days before first dose of study treatment:
• Absolute neutrophil count ≥ 1.0 × 10\^9/L without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection.
• Platelet count ≥ 100 × 10\^9/L without transfusion within 2 weeks of screening laboratory sample collection.
• Hemoglobin ≥ 10.0 g/dL (or 6.2 mmol/L).
• Aspartate transaminase (AST) ≤ 2.5 × upper limit of normal (ULN)
• Alanine aminotransferase (ALT) ≤ 2.5 × ULN.
• Bilirubin ≤ 1.5 × ULN (except participants with Gilbert syndrome who must have total bilirubin \< 3.0 mg/dL).
• Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
• Ambulatory oxygen saturation \>92% on room air at time of screening.

You may not qualify if:

• Any prior systemic therapy for treatment of renal cell carcinoma.
• Any radiation therapy within 4 weeks before the first dose of study treatment.
• Any clear evidence of distant metastases. Enlarged lymph nodes that are planned to be removed during nephrectomy are permitted.
• Clinical pneumonitis or concern for inflammatory lung disease at time of screening.
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) with the intention to treat the disease under study within 2 weeks before first dose of study treatment.
• Other prior malignancy active within the previous year except for locally curable cancers (\>90%) that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or Gleason 6 prostate cancer. Also, indolent malignancies, including but not limited to early-stage chronic lymphocytic leukemia and follicular lymphoma, that don't require anti-cancer treatment, could be allowed after discussion with the medical monitor.
• QTc ≥ 480 msec using Fridericia's correction (QTcF) (based on an average of triplicate recordings).
• Malabsorption condition that would alter the absorption of orally administered medications.
• Patient has had any major cardiovascular event within 6 months prior to study drug administration including but not limited to myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic event, pulmonary embolism, clinically significant ventricular arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) or New York Heart Association Class III or IV heart failure.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a. Cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 2 or greater, unstable angina pectoris, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsades de pointes).
• ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 150 mm Hg systolic or \> 95 mm Hg diastolic despite optimal antihypertensive treatment.
• iii. Any history of stroke (including transient ischemic attack \[TIA\]), myocardial infarction, or other clinically significant ischemic event within 12 months before first dose of study treatment.
• iv. Clinically significant pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous or non-CVA/TIA arterial thromboembolic events within 3 months before to first dose of study treatment. Thrombus felt due to tumor and not a bland thrombus is permitted.
• Note: Subjects with a diagnosis of DVT/PE due to bland thrombus need to be asymptomatic and have at least 4 weeks of anticoagulation before first dose of study treatment.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms

Interventions

zimberelimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Wenxin Xu, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wenxin Xu, MD

CONTACT

617-632-6534; Wenxin_Xu1@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: February 9, 2026
• Study Start: March 9, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): September 30, 2029
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (3)