Study of Optimized Management of Nivolumab Based on Response in Patients With Advanced RCC (OMNIVORE Study)

NCT03203473 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-064
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 8

Brief Summary

This research study is studying two drugs at different time points as a possible treatment for advanced renal cell cancer The drugs involved in this study are: Nivolumab Ipilimumab

Conditions

Renal Cancer

Keywords

Renal Cancer

Outcome Measures

Primary Outcomes (2)

• Percentage of Subjects With Persistent Partial Response (PR) or Complete Response (CR) at 1 Year Since Nivolumab Discontinuation (Arm A Only)

  Persistent PR or CR is defined per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guidelines. Radiologic disease assessment was performed every 8 weeks after patients discontinued nivolumab induction therapy. At 1 year after nivolumab discontinuation, the percentage of patients with persistent PR and CR were reported (for Arm A only).

  From nivolumab discontinuation until 1 year after discontinuation with nivolumab

• Percentage of Subjects With Stable or Progressive Disease (SD/PD) to Nivolumab Induction That Convert to Complete or Partial Response (CR/PR) Upon the Addition of Ipilimumab to Nivolumab (Arm B Only)

  Response is defined per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 guideline. After initiation of ipilimumab, Arm B patients underwent imaging after the first 12 weeks and then every 8 weeks until disease progression. Best overall response during Arm B treatment were summarized with 90% confidence interval.

  For arm B patients, from arm B treatment (nivolumab+ipilimumab) initiation until last imaging assessment during the treatment; assessed up to 22 months.

Secondary Outcomes (9)

• Median Progression Free Survival (Arm B)

  After initiation of Arm B treatment, patients underwent imaging at 12 weeks and then every 8 weeks, up to 22 months.

• 18-month Overall Survival Rate From Initiation of Nivolumab Induction (Overall Cohort)

  Patients were followed from initiation of Nivolumab induction until to death or date last known alive. Kaplan-Meier curve for OS assessed up to 28 months; the 18-month time point estimate for OS was reported.

• Percent of Subjects Who Were Free of Nivolumab Salvage Therapy at 1 Year Since Discontinuation of Nivolumab Induction (Arm A)

  For arm A, from nivolumab discontinuation until 1 year after discontinuation with nivolumab

• Immune Related Objective Response Rate (irORR) in Arm A and Arm B

  For arm A, radiology imaging will be done every 8 weeks until disease progression. For arm B, radiology imaging will be done at 12 weeks and then every 8 weeks until disease progression

• Percentage of Subjects Who Experience Grade 3-4 Treatment-related Adverse Event (TRAE) During the Nivolumab Induction Therapy (Overall Cohort)

  Adverse events during the nivolumab induction were measured from nivolumab initiation until 3 months following the last dose of nivolumab induction or until start of arm B treatment, assessed up to 9 months from nivolumab start

Study Arms (3)

Overall cohort: Initial Primary Treatment with Nivolumab (induction phase)

EXPERIMENTAL

* Therapy with nivolumab IV every 2 weeks * Serial imaging assessments every 8 weeks * After confirmatory scans, patients are assigned to Arm A or Arm B.

Drug: Nivolumab

Arm A: Observation Arm (for patients with persistent response to induction nivolumab)

EXPERIMENTAL

Patients with persistent response (complete or partial response) to induction nivolumab are assigned to Arm A (Observation Arm). * Patients discontinued nivolumab after allocation to Arm A. * Serial imaging assessments every 8 weeks. * If scans persistently show PR/CR, patients remained on observation. * If progressive disease develops, therapy with nivolumab (480 mg IV every 4 weeks) will be resumed. * If there is subsequent progression on nivolumab monotherapy, ipilimumab (1 mg/kg IV every 3 weeks x 2 doses) is added. * If progression after nivolumab + ipilimumab, therapy discontinued. If SD/PR/CR, nivolumab is continued until progression.

Drug: Ipilimumab; Drug: Nivolumab

Arm B: Nivolumab+Ipilimumab then nivolumab alone (for patients with SD/PD to induction nivolumab)

EXPERIMENTAL

Patients with confirmed SD/PD to induction nivolumab are allocated to Arm B (Combination Therapy Arm). * In combination therapy, patients received nivolumab 3 mg/kg and ipilimumab 1 mg/kg intravenously every 3 weeks for two doses. * After then nivolumab will be continued at 480 mg IV every 4 weeks until disease progression. * Arm B patients undergo imaging at 12 weeks and then every 8 weeks.

Drug: Ipilimumab; Drug: Nivolumab

Interventions

Ipilimumab DRUG

YERVOY is thought to work with the body's immune system to increase the activity of T cells and cause the body to attack cancer cells

Also known as: Yervoy

Arm A: Observation Arm (for patients with persistent response to induction nivolumab); Arm B: Nivolumab+Ipilimumab then nivolumab alone (for patients with SD/PD to induction nivolumab)

Nivolumab DRUG

Nivolumab binds to and blocks the activation of PD-1, an Ig superfamily transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs

Also known as: Opdivo

Arm A: Observation Arm (for patients with persistent response to induction nivolumab); Arm B: Nivolumab+Ipilimumab then nivolumab alone (for patients with SD/PD to induction nivolumab); Overall cohort: Initial Primary Treatment with Nivolumab (induction phase)

Eligibility Criteria

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

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Prior use of systemic checkpoint inhibitors for the management of metastatic RCC is excluded. Prior IFN-α or IL-2 is allowed.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 4 weeks of enrollment.
• Treatment with systemic immunosuppressive medications including but not limited to:
• prednisone, dexamethasone, cyclosporin, azathioprine, methotrexate, thalidomide, anti- tumor necrosis factor (TNF) agents within 2 weeks of first study dose.
• Subjects who have received acute, low-dose systemic immunosuppressant medications may be enrolled (such as steroids for acute nausea or cancer-related pain ≤ 10 mg prednisone) may be enrolled sooner than 2 weeks of first study dose.
• Subjects with adrenal insufficiency on physiologic replacement doses of steroids may be enrolled (≤ 10 mg prednisone).
• The use of inhaled, topical, ocular or intra-articular corticosteroids and mineralocorticoids are allowed.
• Treatment with a receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor (e.g. denosumab) within 2 weeks of first study dose.
• Radiotherapy for RCC within 14 days of first study treatment with the exception of a single fraction of radiation administered for palliation of symptoms.
• Known active metastases to the brain, spinal cord or leptomeninges unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks of first study treatment as documented by magnetic resonance imaging (MRI) or computerized tomography (CT) imaging and having no ongoing requirement for steroids.
• Malignancies other than RCC within 5 years of first study treatment with the exception of those with negligible risk of metastases or death and/or treated with expected curative outcome (carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, ductal carcinoma in situ of the breast, non-muscle invasive urothelial carcinoma).
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion protein.
• Known hypersensitivity to any component of the nivolumab or ipilimumab product.
• Any active or recent history (within 6 months of first study dose) of autoimmune disease or syndrome that requires systemic corticosteroids (\>10 mg daily prednisone equivalent) or immunosuppressive medications including but not limited to: myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with anti-phospholipid syndrome, Wegner's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Subjects with vitiligo, controlled type I diabetes mellitus, hypo- or hyperthyroid disease, or surgical adrenal insufficiency requiring hormone replacement therapy are permitted to enroll.

Sponsors & Collaborators

• Toni Choueiri, MD: lead
• Bristol-Myers Squibb: collaborator

Study Sites (8)

University of California, San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Lifespan Comprehensve Cancer Center

Providence, Rhode Island, 02903, United States

Location

University of Utah, Huntsman Cancer Center

Salt Lake City, Utah, 84112, United States

Location

Unviersity of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

Related Publications (3)

• Bootsma M, McKay RR, Emamekhoo H, Bade RM, Schehr JL, Mannino MC, Singh A, Wolfe SK, Schultz ZD, Sperger J, Xie W, Signoretti S, Kyriakopoulos CE, Kosoff D, Abel EJ, Helzer KT, Rydzewski N, Bakhtiar H, Shi Y, Blitzer G, Bassetti M, Floberg J, Yu M, Sethakorn N, Sharifi M, Harari PM, Choueiri TK, Lang JM, Zhao SG. Longitudinal Molecular Profiling of Circulating Tumor Cells in Metastatic Renal Cell Carcinoma. J Clin Oncol. 2022 Nov 1;40(31):3633-3641. doi: 10.1200/JCO.22.00219. Epub 2022 May 26.

  PMID: 35617646 DERIVED

• Bade RM, Schehr JL, Emamekhoo H, Gibbs BK, Rodems TS, Mannino MC, Desotelle JA, Heninger E, Stahlfeld CN, Sperger JM, Singh A, Wolfe SK, Niles DJ, Arafat W, Steinharter JA, Jason Abel E, Beebe DJ, Wei XX, McKay RR, Choueri TK, Lang JM. Development and initial clinical testing of a multiplexed circulating tumor cell assay in patients with clear cell renal cell carcinoma. Mol Oncol. 2021 Sep;15(9):2330-2344. doi: 10.1002/1878-0261.12931. Epub 2021 Mar 3.

  PMID: 33604999 DERIVED

• McKay RR, McGregor BA, Xie W, Braun DA, Wei X, Kyriakopoulos CE, Zakharia Y, Maughan BL, Rose TL, Stadler WM, McDermott DF, Harshman LC, Choueiri TK. Optimized Management of Nivolumab and Ipilimumab in Advanced Renal Cell Carcinoma: A Response-Based Phase II Study (OMNIVORE). J Clin Oncol. 2020 Dec 20;38(36):4240-4248. doi: 10.1200/JCO.20.02295. Epub 2020 Oct 27.

  PMID: 33108238 DERIVED

MeSH Terms

Conditions

Kidney Neoplasms

Interventions

Ipilimumab; Nivolumab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; 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: Toni K Choueiri, MD
• Organization: Dana Farber Cancer Institute

toni_choueiri@dfci.harvard.edu

(617) 632-5456

Study Officials

• Toni K Choueiri, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: May 25, 2017
• First Posted: June 29, 2017
• Study Start: October 26, 2017
• Primary Completion: November 30, 2021
• Study Completion (Estimated): June 28, 2026
• Last Updated: February 6, 2026
• Results First Posted: April 25, 2022

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)