Neoadjuvant Sitravatinib in Combination With Nivolumab in Patients With Clear Cell Renal Cell Carcinoma

NCT03680521 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 516-002
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The study will evaluate the clinical activity of sitravatinib in combination with nivolumab in patients with locally-advanced clear cell renal cell carcinoma (ccRCC) in the neoadjuvant setting prior to nephrectomy.

Conditions

Clear Cell Renal Cell Carcinoma

Keywords

ccRCC; MGCD516; Antineoplastic Agents; Immunologic factors; nivolumab; Tyrosine Kinase Inhibitor; VEGFR; TAM RTKs; PD-1; PD-L1

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Achieved a Point in Time Objective Response (Either Complete or Partial Response [CR or PR]) Prior to Surgery

  Objective response is defined as the percent of participants documented by investigator assessment to have Complete Response (CR) or Partial Response (PR) in accordance with the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions.

  Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

• Point in Time Objective Response Prior to Surgery

  Number and percentage of participants who experienced a response prior to surgery in accordance with RECIST 1.1. * CR is defined as complete disappearance of all baseline target and non-target lesions with the exception of nodal disease; * PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions; * Stable Disease (SD) is concluded when the single point in time response does not qualify for CR, PR or Progressive Disease (PD); * PD is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing nontarget lesions.

  Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Secondary Outcomes (11)

• Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

  Day 1 until 28 days after last dose of study drug or surgery, whichever occurred last (up to a maximum of 13 weeks)

• Blood Plasma Concentrations of Sitravatinib

  Day 1 (pre-dose, and 30 minutes and 4 hours post-dose), Day 15 (pre-dose) and Day 43 (pre-dose)

• Time to Surgery

  Day 1 up to date of surgery (maximum time to surgery was approximately 13 weeks)

• Disease Free Survival (DFS)

  Up to 3 years after surgery (maximum time to surgery was approximately 13 weeks)

• Percentage Change From Baseline in Programmed Death Ligand 1 (PD-L1) Expression in the Tumor

  Baseline to date of surgery (maximum time to surgery was approximately 13 weeks)

Study Arms (1)

Sitravatinib and nivolumab

EXPERIMENTAL

Sitravatinib oral capsule administered daily 2 weeks alone then in combination with nivolumab administered as 240 mg IV every 2 weeks. Total treatment duration: 6-8 weeks prior to planned nephrectomy.

Drug: Sitravatinib; Drug: Nivolumab

Interventions

Sitravatinib DRUG

Sitravatinib oral capsule administered daily for 6-8 weeks in segments 1 and 2.

Sitravatinib and nivolumab

Nivolumab DRUG

Nivolumab administered as 240 mg IV every 2 weeks for 4-6 weeks in segment 2.

Sitravatinib and nivolumab

Eligibility Criteria

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

You may qualify if:

• Imaging results consistent with locally-advanced RCC
• Candidate for partial or complete nephrectomy as part of treatment plan.
• Measurable disease per RECIST version 1.1.
• ECOG performance status 0 or 1.
• Adequate bone marrow and organ function.

You may not qualify if:

• Prior systemic anti-tumor treatment for RCC.
• Patients who are receiving any other investigational agents.
• Clinical status indicating that immediate surgery (within 6 weeks) is warranted regardless of whether neoadjuvant therapy is to be administered, as assessed by the treating surgeon.
• Inability to undergo baseline tumor biopsy.
• Active or prior documented autoimmune or immunocompromising conditions.
• Uncontrolled hypertension.

Sponsors & Collaborators

• Mirati Therapeutics Inc.: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

sitravatinib; Nivolumab

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

Results Point of Contact

• Title: Sr. Clinical Operations Trial Manager
• Organization: Mirati Therapeutics

hallinm@mirati.com

858-332-3540

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: September 21, 2018
• Study Start: October 10, 2018
• Primary Completion: April 27, 2020
• Study Completion: May 18, 2023
• Last Updated: October 4, 2023
• Results First Posted: May 19, 2021

Record last verified: 2023-09

Locations

US (1)