Sitravatinib and Nivolumab for the Treatment of Metastatic or Advanced Clear Cell Renal Cell Cancer

NCT04904302 | Terminated Phase 2 FDA Drug

• 2 other identifiers: 2021-0057NCI-2021-03344
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial investigates the effect of sitravatinib and nivolumab in treating patients with clear cell renal cell cancer that has spread to other places in the body (metastatic/advanced). Sitravatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving sitravatinib and nivolumab may kill more tumor cells.

Conditions

Stage IV Renal Cell Cancer AJCC v8; Advanced Clear Cell Renal Cell Carcinoma; Metastatic Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Objective response rate

  Will be defined as complete response + partial response. Will be defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

  At 24 weeks

• Disease control rate

  Will be defined by RECIST 1.1.

  At 24 weeks

Secondary Outcomes (5)

• Overall survival

  At 1 year

• Progression free survival

  At 1 year

• Duration of response

  At 1 year

• Incidence of adverse events

  Up to 6 years

• Health-related quality-of-life (QOL)

  Up to 24 weeks

Study Arms (1)

Treatment (sitravatinib, nivolumab)

EXPERIMENTAL

Patients receive sitravatinib PO QD and nivolumab IV over 30 minutes on day 1. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Sitravatinib

Interventions

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (sitravatinib, nivolumab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (sitravatinib, nivolumab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (sitravatinib, nivolumab)

Sitravatinib DRUG

Given PO

Also known as: MGCD516

Treatment (sitravatinib, nivolumab)

Eligibility Criteria

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

You may qualify if:

• Patients with histologically or cytologically confirmed metastatic/advanced clear cell RCC, or RCC with a clear cell component, who have received 1 or 2 prior lines of treatment in the advanced or metastatic setting, and the most recent treatment must include a PD-1 or PD-L1 CPI, cabozantinib, or lenvatinib. Examples of acceptable prior regimens include: nivolumab plus ipilimumab (cohort A), pembrolizumab plus axitinib, avelumab plus axitinib, or VEGF-targeted monotherapy followed by nivolumab monotherapy (cohort B), or cabozantinib or lenvatinib with or without everolimus, received alone sequentially before PD-1/PD-L1 inhibitors, or in combination with CPIs (cohort C)
• There must be evidence of progression on or after treatment (at any point after completing prior therapy) with a PD-1/PD-L1-containing regimen as the last treatment received within 6 months of enrollment
• Patients must have at least one measurable site of disease, defined as a lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) and measures \>= 15 mm with conventional techniques or \>= 10 mm with more sensitive techniques such as magnetic resonance imaging (MRI) or spiral computed tomography (CT) scan. If the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation
• Karnofsky performance status \>= 70
• Age \>= 18 years
• Hemoglobin \>= 9 g/dl (treatment allowed)
• May receive transfusion
• Absolute neutrophil count \>= 1,000/uL
• Platelets \>= 75,000/uL
• Total bilirubin =\< 1.5 mg/dL
• For patients with Gilbert's disease, total bilirubin should =\< 3 mg/dL (=\< 51.3 umol/L)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) or alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal (ULN), except in known hepatic metastasis, wherein may be \< 5 x ULN
• Serum Creatinine =\< 1.5 x ULN (as long as patient does not require dialysis)
• If creatinine is not \< 1.5 x ULN, then calculate by Cockcroft-Gault methods or local institutional standard and creatinine clearance (CrCl) must be \>= 40 mL/kg/1.73 m\^2
• Institutional normalized ratio (INR) and partial thromboplastin time (PTT) =\< 1.5 x ULN prior to study entry. Therapeutic anticoagulation is permitted if: on a stable dose of low molecular weight heparin (LMWH) for \> 2 weeks (14 days) at the time of enrollment or on a direct oral anticoagulant (DOAC) for \> 2 weeks at time of enrollment

You may not qualify if:

• Patients must not have any other malignancies within the past 2 years except for in situ carcinoma of any site, adequately treated (without recurrence post-resection or post- radiotherapy) carcinoma of the cervix or basal or squamous cell carcinomas of the skin, or active non-threatening second malignancy that would not, in the investigator's opinion, potentially interfere with the patient's ability to participate and/or complete this trial. Examples include but not limited to: urothelial cancer grade Ta or T1, adenocarcinoma of the prostate treated by active surveillance
• Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks (14 days) from enrollment into this study (including chemotherapy and targeted therapy) are excluded. Also, patients who have completed palliative radiation therapy more than 14 days prior to the first dose of sitravatinib are eligible
• Patients who had a major surgery or significant traumatic injury (injury requiring \> 28 days to heal) within 28 days of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia), or patients that are expected to require major surgery during the course of the study
• Patients with a prior history of grade 3 or worse immune-related adverse events attributed to CPIs (PD-1, PD-L1, or CTLA-4), except endocrine adverse events with appropriate hormone replacement or asymptomatic amylase/lipase elevations
• Active or prior documented autoimmune disease, as follows:
• Inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
• Interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis that required steroid treatment, or any evidence of clinically active ILD.
• Other medically important autoimmune disease within 2 years before first dose of study treatment. Note: Patients with type 1 diabetes, vitiligo, Graves' disease requiring only hormone replacement, residual hypothyroidism requiring only hormone replacement, or psoriasis or Sjogren's syndrome not requiring systemic treatment are permitted
• Immunocompromising conditions, as follows:
• Known acute or chronic human immunodeficiency virus (HIV) infection
• History of primary immunodeficiency
• History or allogeneic transplant
• Current or prior use of immunosuppressive medication within 28 days before the first dose of study treatment, with the exception of topical, ocular, intranasal, and inhaled corticosteroids, or systemic corticosteroids at an equivalent dose =\< 10 mg of prednisone daily
• Any underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea, uncontrolled nausea, vomiting, malabsorption syndrome or small bowel resection that may significantly alter the absorption of sitravatinib
• Patients receiving any concomitant systemic therapy for renal cell cancer are excluded

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (2)

Indiana University Hospital / IU Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Hahn AW, Adra N, Vaishampayan U, Xiao L, Dizman N, Yuan Y, Mukhida SS, Campbell MT, Gao J, Zurita AJ, Jonasch E, Tannir NM, Shah AY, Msaouel P. A phase II trial of sitravatinib + nivolumab after progression on immune checkpoint inhibitor in patients with metastatic clear cell RCC. Oncologist. 2025 Apr 4;30(4):oyaf053. doi: 10.1093/oncolo/oyaf053.

  PMID: 40212021 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma; Carcinoma, Renal Cell

Interventions

Nivolumab; sitravatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney 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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Pavlos Msaouel

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2021
• First Posted: May 27, 2021
• Study Start: May 3, 2022
• Primary Completion: March 11, 2026
• Study Completion: March 11, 2026
• Last Updated: March 20, 2026

Record last verified: 2026-03

Locations

US (2)